776 lines
60 KiB
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776 lines
60 KiB
HTML
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<head><title>Altitude and Mortality</title></head>
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<body>
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<h1>
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Altitude and Mortality
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</h1>
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<p></p>
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<p>
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<em>Breathing pure oxygen lowers the oxygen content of tissues; breathing rarefied air, or air with carbon
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dioxide, oxygenates and energizes the tissues; if this seems upside down, it's because medical
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physiology has been taught upside down. And respiratory physiology holds the key to the special
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functions of all the organs, and to many of their basic pathological changes.</em>
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</p>
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<p>
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<strong><em>Stress, shock, inflammation, aging, and organ failure are, in important ways, respiratory
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problems.</em></strong>
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</p>
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Definitions <strong>
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Haldane effect:
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</strong>Oxygen displaces carbon dioxide from hemoglobin, in proportion to its partial (specific) pressure.
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<strong>
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Bohr effect:</strong> Carbon dioxide (or acidity) displaces oxygen from hemoglobin. <strong>
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Lactic acidemia:
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</strong>The presence of lactic acid in the blood. <strong>
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Alkalosis:</strong> A pH of the blood above 7.4. <strong>
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Acidosis:
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</strong>A blood pH below 7.4. <strong>
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Lactate paradox:</strong> The reduced production of lactic acid at a given work rate at high altitude.
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Muscle work efficiency may be 50% greater at high altitude. ATP wastage is decreased.<p></p>
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<p>
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There are some popular medical ideas that obstruct clear thinking about respiration. One is that high
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altitude deprives you of oxygen, and is likely to be bad for people with heart disease and cancer. Another
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is that breathing pure oxygen helps sick people to oxygenate their tissues while exerting less effort in
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breathing. These are both exactly wrong, and the errors have been explored in quite a few publications, but
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the ideas persist in the culture to such a degree that our <strong><em>perceptions and intuitions
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</em></strong>have been misled, making closely related things seem to be unrelated. In this culture, it
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is hard to see that heart disease, cancer, and cataracts all involve a crucial respiratory defect, with the
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production of too much lactic acid and too little carbon dioxide, which leads to a "swelling
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pathology"<strong>:</strong> A pathological retention of water. The swollen heart beats poorly, the swollen
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lens turns milky, other cells divide rapidly as a result of swelling.
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</p>
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<p>
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People who live at very high altitudes live significantly longer<strong>;</strong> they have a lower
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incidence of cancer (Weinberg, et al., 1987) and heart disease (Mortimer, et al., 1977), and other
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degenerative conditions, than people who live near sea level. As I have written earlier, I think the lower
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energy transfer from cosmic radiation is likely to be a factor in their longevity, but several kinds of
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evidence indicate that it is the lower oxygen pressure itself that makes the biggest contribution to their
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longevity.
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</p>
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<p>
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"Mountain sickness" is a potentially deadly condition that develops in some people when they ascend too
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rapidly to a high altitude. Edema of the lungs and brain can develop rapidly, leading to convulsions and
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death. The standard drug for preventing it is acetazolamide, which inhibits carbonic anhydrase and causes
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carbon dioxide to be retained, creating a slight tendency toward acidosis. This treatment probably mimics
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the retention of carbon dioxide that occurs naturally in altitude adapted people. The reasons for mountain
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sickness, and the reasons for the low incidence of heart disease, cancer, cataracts, etc., at high altitude,
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offer clues to the prevention of death and deterioration from many other causes.
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</p>
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<p>
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When the weather in a particular place is cool, sunny and dry (which in itself is very good for the health)
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the atmospheric pressure usually is higher than average. Although sunny dry weather is healthful,<strong>
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periods of higher pressure correspond to an increased incidence of death</strong>
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from heart disease and strokes.
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</p>
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<p>
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The Haldane-Bohr effect describes the fact that oxygen and carbon dioxide destabilize each other"s binding
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to hemoglobin. When oxygen pressure is high, the blood releases its carbon dioxide more easily. In stormy
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weather, or at high altitude, the lower oxygen pressure allows the body to retain more carbon dioxide.
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Carbon dioxide, produced in the cells, releases oxygen into the tissues, relaxes blood vessels, prevents
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edema, eliminates ammonia, and increases the efficiency of oxidative metabolism.
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</p>
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<p>
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Hyperventilation, breathing excessively and causing too much carbon dioxide to be lost, is similar to being
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in the presence of too much oxygen<strong>;</strong> it"s similar to being at low altitude with high
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atmospheric pressure, only worse. Therefore, the physiological events produced by hyperventilation can give
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us an insight into what happens when the atmospheric pressure is low, by looking at the events in reverse.
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Likewise, breathing 100% oxygen has known harmful consequences, which are very similar to those produced by
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hyperventilation.
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</p>
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<p>
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Hyperventilation is defined as breathing enough to produce respiratory alkalosis from the loss of carbon
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dioxide. Lactic acid is produced in response to the alkalosis of hyperventilation.
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</p>
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<p>
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Breathing too much oxygen displaces too much carbon dioxide, provoking an increase in lactic acid<strong
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>;</strong> too much lactate displaces both oxygen and carbon dioxide. Lactate itself tends to suppress
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respiration.
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</p>
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<p>
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Oxygen toxicity and hyperventilation create a systemic deficiency of carbon dioxide. It is this carbon
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dioxide deficiency that makes breathing more difficult in pure oxygen, that impairs the heart"s ability to
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work, and that increases the resistance of blood vessels, impairing circulation and oxygen delivery to
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tissues. In conditions that permit greater carbon dioxide retention, circulation is improved and the heart
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works more effectively. Carbon dioxide inhibits the production of lactic acid, and lactic acid lowers carbon
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dioxide's concentratrion in a variety of ways..
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</p>
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<p>
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When carbon dioxide production is low, because of hypothyroidism, there will usually be some lactate
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entering the blood even at rest, because adrenalin and noradrenalin are produced in large amounts to
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compensate for hypothyroidism, and the adrenergic stimulation, besides mobilizing glucose from the glycogen
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stores, stimulates the production of lactate. The excess production of lactate displaces carbon dioxide from
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the blood, partly as a compensation for acidity. The increased impulse to breath ("ventilatory drive")
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produced by adrenalin makes the problem worse, and lactate can promote the adrenergic response, in a vicious
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circle..
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</p>
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<p>
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Since the 1920s when A. V. Hill proposed that the prolonged increase in oxygen consumption after a short
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period of intense work, the "oxygen debt," was equivalent to the amount of lactic acid that had entered the
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circulation from the muscles" anaerobic work, and that it had to be disposed of by oxidative processes,
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physiology textbooks have given the impression that lactic acid accumulation was exactly the same as the
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oxygen debt. In reality, several things are involved, especially the elevation of temperature produced by
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the intense work. Increased temperature raises oxygen consumption independently of lactic acid, and lower
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temperature decreases oxygen consump-tion, even when lactic acid is present.
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</p>
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<p>
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The idea of the "oxygen debt" produced by exercise or stress as being equivalent to the accumulation of
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lactic acid is far from accurate, but it"s true that activity increases the need for oxygen, and also
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increases the tendency to accumulate lactic acid, which can then be disposed of over an extended time, with
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the consumption of oxygen. This relationship between work and lactic acidemia and oxygen deficit led to the
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term "lactate paradox" to describe the lower production of lactic acid during maximal work at high altitude
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when people are adapted to the altiude. Carbon dioxide, retained through the Haldane effect, accounts for
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the lactate paradox, by inhibiting cellular excitation and sustaining oxidative metabolism to consume
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lactate efficiently.
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</p>
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<p>
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The loss of carbon dioxide from the lungs in the presence of high oxygen pressure, the shift toward
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alkalosis, by the Bohr-Haldane effect increases the blood"s affinity for oxygen, and restricts its delivery
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to the tissues, but because of the abundance of oxygen in the lungs, the blood is almost competely saturated
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with oxygen.
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</p>
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<p>
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At high altitude, the slight tendency toward carbon dioxide-retention acidosis decreases the blood"s
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affinity for oxygen, making it more available to the tissues. It happens that lactic acid also affects the
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blood"s oxygen affinity, though not as strongly as carbon dioxide. <strong>
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However, lactic acid doesn"t vaporize as the blood passes through the lungs, so its effect on the lungs"
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ability to oxygenate the blood is the opposite of the easily exchangeable carbon dioxide"s.
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</strong>
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Besides<strong> </strong>dissociating oxygen from hemoglobin, lactate also displaces carbon dioxide from its
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(carbamino) binding sites on hemoglobin. If it does this in hemoglobin, it probably does it in many other
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places in the body.
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</p>
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<p>
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According to Meerson, ascending more than 200 feet per day produces measurable stress. People seldom notice
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the effects of ascending a few thousand feet in a day, but it has been found that a large proportion of
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people have bleeding into the retina when they ascend to 10,000 feet without adequate adaptation.
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Presumably, similar symptomless bleeding occurs in other organs, but the retina can be easily inspected.
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</p>
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<p>
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If hypothyroid people, with increased adrenalin and lactate, are hyperventilating even at rest and at sea
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level, when they go to a high altitude where less oxygen is available, and their absorption of oxygen is
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impaired by lactic acidemia, <strong>their "oxygen debt," conceived as circulating lactic acid, is easily
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increased, intensifying their already excessive "ventilatory drive," and in proportion to the lactic
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acid oxygen debt, oxygen absorption is further inhibited.</strong>
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</p>
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<p>
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The lactic acid has to be disposed of, but their ability to extract oxygen is reduced. The poor oxygenation,
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and the increased lactic acid and free fatty acids cause blood vessels to become leaky, producing edema in
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the lungs and brain. <strong>This is very similar to the "multiple organ failure" that occurs in
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inflammatory conditions, bacteremia, congestive heart failure, cancer, and trauma.</strong>
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</p>
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<p>
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<strong>Otto Warburg established that lactic acid production even in the presence of oxygen is a fundamental
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property of cancer.</strong> It is, to a great degree, the lactic acid which triggers the defensive
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reactions of the organism, leading to tissue wasting from excessive glucocorticoid hormone. The cancer"s
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production of lactic acid creates the same kind of internal imbalance produced by hyperventilation, and if
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we look at the physiology of hyperventilation in the light of Warburg"s description of cancer,
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hyperventilation imitates cancer metabolism, by producing lactic acid "even in the presence of oxygen."
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Lactate, a supposedly benign metabolite of the cancer cells, which appears in all the other degenerative
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conditions, including obesity, diabetes, Alzheimer"s disease, multiple sclerosis, is itself a central factor
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in the degenerative process.
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</p>
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<p>
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Working out the mechanisms involved in susceptibility to altitude sickness will clarify the issues involved
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in the things that cause most people to die. At first, all of these changes occur in the regulatory systems,
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and so can be corrected.
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</p>
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<p>
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The vitality of the mitochondria, their capacity for oxidative energy production, is influenced by nutrition
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and hormones. In healthy people, mitochondria work efficiently at almost any altitude, but people with
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damaged or poorly regulated mitochondria are extremely susceptible to stress and hyperventilation.
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Progesterone, testosterone, and thyroid (T3 and T2) are protective of normal mitochondrial function, by both
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local and systemic effects.
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</p>
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<p>
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The changes that occur in malnutrition and hypothyroidism affect the mitochondria in a multitude of ways,
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besides the local effects of the thyroid and progesterone deficiency.
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</p>
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<p>
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Increased estrogen, nitric oxide, excitatory amino acids, cortisol, lactate, free unsaturated fatty acids,
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prolactin, growth hormone, histamine, serotonin, tumor necrosis factor and other pro-inflammatory cytokines
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and kinins, and a variety of prostaglandins and eicosanoids, have been identified as anti-mitochondrial,
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anti-respiratory agents. Edema itself can be counted among these agents.<strong> </strong>
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(Carbon dioxide itself directly reduces tissue edema, as can be seen in studies of the cornea.)<strong>
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Thyroid, progesterone, magnesium, glucose, and saturated fatty acids are among the central protective
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elements.</strong>
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</p>
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<p>
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The similarity of the changes occurring under the influence of estrogen excess, oxygen deprivation, aging,
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and ionizing radiation are remarkable. People who think that radiation"s biological effects are mainly on
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the DNA, and that estrogen acts through "estrogen receptors," aren"t interested in the parallels, but the
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idea of a common respiratory defect, activating common pathways, suggests that there is something useful in
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the perception that irradiation, hypoxia, and aging have estrogenic effects.
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</p>
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<p>
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Irradiation by ultraviolet, gamma, or x-rays, and even by blue light, is damaging to mitochondrial
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respiration. All of the ionizing radiations produce immediate and lingering edema, which continues to damage
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metabolism in a more or less permanent way, apart from any detectable mutagenic actions. The amount of water
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taken up following irradiation can be 20% to 30% of the normal weight, which is similar to the amount of
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swelling that intense work produces in a muscle, and to the weight increase under hormonal imbalances. The
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energy changes produced by irradiation in, for example, the heart, appear to accelerate the changes produced
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by aging. Since unsaturated fats accumulate in the respiratory system with aging, and are targets for
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radiation damage, the involvement of these fats in all sorts of antirespiratory degenerative processes
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deserves more attention. Darkness, like irradiation, excess lactate, and unsaturated fats, has the
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diabetes-like effect of greatly reducing the ability of muscle to absorb sugar, while light stimulates
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respiration..
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</p>
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<p>
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When the ideas of "stress," "respiratory defect," and "hyperventilation" are considered together, they seem
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practically interchangeable.
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</p>
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<p>
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The presence of lactic acid, which indicates stress or defective respiration, interferes with energy
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metabolism in ways that tend to be self-promoting. Harry Rubin"s experiments demonstrated that cells become
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cancerous before genetic changes appear. <strong>The mere presence of lactic acid can make cells more
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susceptible to the transformation into cancer cells.
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</strong>(Mothersill, et al., 1983.) The implications of this for the increased susceptibility to cancer
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during stress, and for the increased resistance to cancer at high altitude, are obvious.
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</p>
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<p>
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Blocking the production of lactic acid can make cells more resistant (Seymour and Mothersill, 1988)<strong
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>;</strong>
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if lactic acid were merely a useful fuel, it"s hard to see how poisoning its formation could improve cell
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survival. But it happens to be an energy-disruptive fuel, interfering with carbon dioxide metabolism, among
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other things.
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</p>
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<p>
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Hyperventilation is present in hypothyroidism, and is driven by adrenalin, lactate, and free fatty acids.
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Free fatty acids and lactate impair glucose use, and promote edema, especially in the lungs. Edema in the
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lungs limits oxygen absorption. Swelling of the brain, resulting from increased vascular permeability and
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the entry of free fatty acids, reduces its circulation and oxygenation<strong>;</strong> lactic acidemia
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causes swelling of glial cells. Swelling of the endothelium increases vascular resistance by making the
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channel narrower, eventually affecting all organs. Cells of the immune system release tumor necrosis factor
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and other inflammatory cytokines, and the bowel becomes more permeable, allowing endotoxin and even bacteria
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to enter the blood. Endotoxin impairs mitochondria, increases estrogen levels, causes Kupffer cells in the
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liver to produce more tumor necrosis factor, etc.. Despite its name, tumor necrosis factor stimulates the
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growth and metastasis of some types of cancer. Dilution of the body fluids, which occurs in hypothyroidsim,
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hyperestrogenism, etc., stimulates tumor growth.
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</p>
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<p>
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The inflammatory factors that can promote cell growth can, with just slight variation, deplete cellular
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energy to the extent that the cells die from the energetic cost of the repair process, or mutate from
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defective repairs. Niacinamide can have an "antiinflammatory" function, preventing death from multiple organ
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failure, by interupting the reactions to nitric oxide and peroxynitrile (Cuzzocrea, et al., 1999). The
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cells" type, environment, and history determine the different outcomes.
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</p>
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<p>
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Cataracts, cancer, congestive heart failure, seemingly such different degenerative problems, have the same
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sort of metabolic problem, leading to the abnormal absorption of water by cells, disrupting their normal
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functions.
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</p>
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<p>
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The same simple metabolic therapies, such as thyroid, progesterone, magnesium, and carbon dioxide, are
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appropriate for a great range of seemingly different diseases. Other biochemicals, such as adenosine and
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niacinamide, have more specific protective effects, farther downstream in the "cascade" effects of stress.
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</p>
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<p>
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There are many little cliches in the medical culture that prevent serious thought about integral
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therapy<strong>:</strong> "Progesterone is the pregnancy hormone," "thyroid makes your heart work too hard,"
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"thyroid uncouples mitochondrial phosphorylation," "magnesium has nothing to do with thyroid or
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progesterone," "lactate provides energy," etc. But many of these minor cliches are held in place by deep
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theoretical errors about the nature of cells and organisms. Once those have been corrected, there should be
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progress toward more powerful integral therapies.
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</p>
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<p><h3>REFERENCES</h3></p>
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<p>
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Cell Biol Int Rep 1983 Nov;7(11):971-80.<strong>
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Lactate-mediated changes in growth morphology and transformation frequency of irradiated C3H 10T1/2
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cells.</strong> Mothersill C, Seymour CB, Moriarty M. Treatment of mammalian cells with lactate or
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inhibitors of glycolysis alters their radiation response, particularly in the low dose region of the dose
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response curve. The occurrence of <strong>both high lactate levels and high glycolytic metabolism in
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tumours</strong> is well known and therefore the effect of lactate on a cell line sensitive to radiation
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induced transformation was examined using a single exposure to Cobalt 60 gamma rays as the carcinogen
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challenge. The results indicate that cells treated with <strong>
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5mM lactate before irradiation exhibit changes in morphology and growth rate and that the transformation
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frequency is increased by three to ten fold following 24 hours lactate treatment just prior to
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irradiation.
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</strong>
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Examination of radiation survival curves showed a positive correlation between transformation frequency and
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size of the shoulder, but increasing transformation frequency was associated with a decrease in Do. A
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mechanism involving altered Redox potential in lactate treated cells is suggested. The results are discussed
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in terms of their possible significance for radiotherapy.
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</p>
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<p>
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<strong>Radiat Environ Biophys 1988;27(1):49-57. The effect of glycolysis</strong>
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<strong>
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inhibitors on the radiation response of CHO-K1 cells. Seymour CB, Mothersill C Saint Luke's Hospital,
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Rathgar, Dublin, Ireland. Exposure of CHO-K1 cells to three different inhibitors of glycolysis, prior to
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treatment with a single dose of ionising radiation, reduced their survival. The effects were
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concentration-dependent but occurred under all conditions where cells were exposed to the inhibitors
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prior to irradiation. The results are similar to those obtained by this group when glycolysis was
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altered using analogues of D-glucose or by blocking the pyruvate----lactate reaction using added lactate
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or oxamate. They support data from other workers suggesting a role for energy metabolism in the final
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expression of radiation damage.
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</strong>
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</p>
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<p>
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Crit Care Med 1999 Aug;27(8):1517-23. <strong>Protective effect of poly(ADP-ribose) synthetase inhibition on
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multiple organ failure after zymosan-induced peritonitis in the rat.</strong> Cuzzocrea S, Zingarelli B,
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Costantino G, Sottile A, Teti D, Caputi AP
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</p>
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<p>
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Eur J Cancer 1975 May;11(5):365-371. <strong>Cancer and altitude. Does intracellular pH regulate cell
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division?</strong> Burton AC.<strong> </strong>
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</p>
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<p>
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<strong>Monaldi Arch Chest Dis 1999 Aug;54(4):365-72. The pathophysiology of hyperventilation syndrome.
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Folgering H.</strong> Dept Pulmonology Dekkerswald, University of Nijmegen, Groesbeek, The Netherlands..
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<strong>Hyperventilation is defined as breathing in excess of the metabolic needs of the body, eliminating
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more carbon dioxide than is produced, and, consequently, resulting in respiratory alkalosis and an
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elevated blood pH.</strong> The traditional definition of hyperventilation syndrome describes "a
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syndrome, characterized by a variety of somatic symptoms induced by physiologically inappropriate
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hyperventilation and usually reproduced by voluntary hyperventilation". The spectrum of symptoms ascribed to
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hyperventilation syndrome is extremely broad, aspecific and varying. They stem from virtually every tract,
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and can be caused by physiological mechanisms such as low Pa,CO2, or the<strong>
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increased sympathetic adrenergic tone.</strong> Psychological mechanisms also contribute to the
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symptomatology, or even generate some of the symptoms. Taking the traditional definition of hyperventilation
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syndrome as a starting point, there should be three elements to the diagnostic criterion: 1) the patient
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should hyperventilate and have low Pa,CO2, 2) somatic diseases causing hyperventilation should have been
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excluded, and 3) the patient should have a number of complaints which are, or have been, related to the
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hypocapnia. Recent studies have questioned the tight relationship between hypocapnia and complaints.
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However, the latter can be maintained and/or elicited when situations in the absence of hypocapnia in which
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the first hyperventilation and hypocapnia was present recur. Thus, the main approach to diagnosis is the
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detection of signs of (possible) dysregulation of breathing leading to hypocapnia. The therapeutic approach
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to hyperventilation syndrome has several stages and/or degrees of intervention: psychological counselling,
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physiotherapy and relaxation, and finally drug therapy. Depending on the severity of the problem, one or
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more therapeutic strategies can be chosen.
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</p>
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<p>
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N Engl J Med 1977 Mar 17;296(11):581-585.<strong>
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Reduction in mortality from coronary heart disease in men residing at high altitude.</strong> Mortimer
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EA Jr, Monson RR, MacMahon B In New Mexico, where inhabited areas vary from 914 to over 2135 m above sea
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level, we compared age-adjusted mortality rates for arteriosclerotic heart disease for white men and women
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for the years 1957-1970 in five sets of counties, grouped by altitude in 305-m (1000-foot) increments. The
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results show a serial decline in mortality from the lowest to the highest altitude for males but not for
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females. Mortality rates for males residing in the county groups higher than 1220 m in order of ascending
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altitude <strong>were 98, 90, 86 and 72 per cent of that for the county group below 1220-m altitude (P less
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than 0.0001).</strong> The results do not appear to be explained by artifacts in ascertainment,
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variations in ethnicity or urbanization. A possible explanation of the trend is that adjustment to residence
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at high altitude is incomplete and daily activities therefore represent greater exercise than when
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undertaken at lower altitudes.
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</p>
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<p>
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Br Med J 1980 Jan 5;280(6206):5. Cardiovascular mortality and altitude.
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</p>
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<p>
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Radiat Res 1987 Nov;112(2):381-390. <strong>Altitude, radiation, and mortality from cancer and heart
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disease.</strong> Weinberg CR, Brown KG, Hoel DG. The variation in background radiation levels is an
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important source of information for estimating human risks associated with low-level exposure to ionizing
|
|
radiation. Several studies conducted in the United States, correlating mortality rates for cancer with
|
|
estimated background radiation levels, found an unexpected inverse relationship. Such results have been
|
|
interpreted as suggesting that low levels of ionizing radiation may actually confer some benefit. An
|
|
environmental factor strongly correlated with background radiation is altitude. Since there are important
|
|
physiological adaptations associated with breathing thinner air, such changes may themselves influence risk.
|
|
We therefore fit models that simultaneously incorporated altitude and background radiation as predictors of
|
|
mortality. The <strong>negative correlations with background radiation</strong> seen for <strong>mortality
|
|
from arteriosclerotic heart disease and cancers of the lung, the intestine, and the breast</strong>
|
|
disappeared or became positive once altitude was included in the models. <strong>By contrast, the
|
|
significant negative correlations with altitude persisted with adjustment for radiation. Interpretation
|
|
of these results is problematic, but recent evidence implicating reactive forms of oxygen in
|
|
carcinogenesis and atherosclerosis may be relevant. We conclude that the cancer correlational studies
|
|
carried out in the United States using vital statistics data do not in themselves demonstrate a lack of
|
|
carcinogenic effect of low radiation levels, and that reduced oxygen pressure of inspired air may be
|
|
protective against certain causes of death.
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
Biull Eksp Biol Med 1993 Jun;115(6):576-578. <strong>[The effect of high-altitude ecological and
|
|
experimental stresses on the thrombocyte-vascular wall system].</strong> [Article in Russian].
|
|
Bekbolotova AK, Lemeshenko VA, Aliev MA. Experiments in animals (rats) and examinations of the population of
|
|
high-altitude shepherds were used to study the functional system "Thrombocytes-Vessel Wall" (STVW) for
|
|
evaluation of the organism ecological adaptation to "pure" high-altitude stress, with and without
|
|
combination with experimental-adrenergic cardionecrosogenic stress (ACNS, in rats). The adaptive increase of
|
|
antiaggregation prostacyclin activity of the aorta in rats and PGI2 reaction of vessels in human population
|
|
of high-altitude in mountains (2000, 3000-3500 m) were found to be a common biologist regularity. The<strong
|
|
>
|
|
adaptive increase of coronary reserve of the heart and vasodilatator-antiaggregation status in
|
|
high-altitude shepherds correlated with an increase of antiaggregation activity of the aorta and
|
|
decrease of spontaneous aggregation of the thrombocytes in rats under conditions of more prolonged
|
|
adaptation to high-altitude ecological stress.
|
|
</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Diabetologia 1982 Jun;22(6):493. <strong>Measurement of glycosylated haemoglobin at high altitudes.</strong>
|
|
Paisey R, Valles V, Arredondo G, Wong B, Lozano-Castaneda O.
|
|
</p>
|
|
<p>
|
|
<strong>[Change in the ultrastructure of rat myocardium under the influence of 12-months' adaptation to high
|
|
altitude]</strong> Zhaparov B; Mirrakhimov MM. Biull Eksp Biol Med, 1977 Jul, 84:7, 109-12. The right
|
|
and left ventricle myocardium of rats was studied in the course of a 12-month period of adaptation to high
|
|
altitude (3200 m above the sea level). A long-term exposure of the animals to the high altitude led the
|
|
development of ventricular hypertrophy mostly of the right, and partly of the left ventricle.<strong>
|
|
Hyperplasia and hypertrophy of individual organellae, particularly mitochondria</strong>, were found in
|
|
most cardiomyocytes of both ventricles. In animals adapted to the high altitude the mitochondrial succinic
|
|
dehydrogenase activity was more pronounced than in control ones. The results obtained testified to the
|
|
enhanced intracellular metabolism reflecting myocardial compensatory adaptive responses.
|
|
</p>
|
|
<p>
|
|
<strong>[Morphologic characteristics of the hearts of argali continuously dwelling at high mountain
|
|
altitudes]</strong>, Zhaparov B; Kamitov SKh; Mirrakhimov MM, Biull Eksp Biol Med, 1980 Apr, 89<strong
|
|
>:</strong>4, 498-501 The hearts of argali [wild sheep] living at 3800-5000 m above the sea level were
|
|
examined.<strong>
|
|
Macroscopy showed complete absence of fatty tissue under the epicardium.</strong> Increased number of
|
|
the capillaries surrounding cardiomyocytes, intercalated discs in many zones of the myocardium, sharp
|
|
thickening giving pronounced cross lines of myofibrils were revealed on semithin and ultrathin sections. The
|
|
data obtained demonstrate specificity of the heart structure of argali and are<strong>
|
|
discussed from the standpoint of increased compensatory-adaptive changes in the test organ, these
|
|
changes being associated with its enhanced function provoked by high altitude conditions.
|
|
</strong>
|
|
</p>
|
|
|
|
<p>
|
|
J Dev Physiol 1990 Sep;14(3):139-46. <strong>Effect of lactate and beta-hydroxybutyrate infusions on brain
|
|
metabolism in the fetal sheep.</strong>
|
|
<hr />
|
|
<strong>Despite large increases in fetal arterial lactate and beta-hydroxybutyrate during the respective
|
|
infusions, no significant uptake of either substrate was demonstrated. However during both types of
|
|
infusion, the brain arterio-venous difference for glucose decreased 30% (P less than 0.05). Since the
|
|
brain arterio-venous difference for oxygen was unchanged, and blood flow to the cerebral hemispheres
|
|
(measured in 11 studies) was also unchanged, the infusions appeared to cause a true decrease in brain
|
|
glucose uptake. This decrease paralleled the rise in lactate concentration during lactate infusions, and
|
|
the rise in lactate and butyrate</strong> concentrations during the butyrate infusions. Both substrates
|
|
have metabolic actions that may inhibit brain glucose uptake. <strong>We speculate that the deleterious
|
|
effects of high lactate and ketone states in the perinatal period may in part be due to inhibition of
|
|
brain glucose uptake.</strong>
|
|
</p>
|
|
<p>
|
|
Hypertens 1995 Feb;9(2):119-22. <strong>
|
|
Pressor effect of hyperventilation in healthy subjects.</strong> Todd GP, Chadwick IG, Yeo WW, Jackson
|
|
PR, Ramsay LE University Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, UK
|
|
Hyperventilation is an important feature of panic disorder, and an association has been reported between
|
|
panic disorder and hypertension. We have examined the effect of hyperventilation on the blood pressure (BP)
|
|
of healthy subjects. Twenty six subjects were randomised in a balanced two-period cross-over study to
|
|
compare the effects of hyperventilation with that of normal breathing on sitting BP, heart rate and the
|
|
electrocardiogram. Each study phase lasted 40 min, with 15 min of baseline observation, 5 min of
|
|
hyperventilation or normal breathing, and 20 min of continued<strong>
|
|
observation. Hyperventilation significantly increased SBP by 8.9 mm Hg (95% CI 3.8-13.8, P < 0.01),
|
|
diastolic blood pressure by 8.2 mm Hg (95% CI 1.7-14.7, P < 0.05), mean arterial pressure by 10.0 mm
|
|
Hg (95% CI 3.3-16.7, P < 0.01) and heart rate by 36 beats/min (95% CI 31-44, P < 0.01). The
|
|
changes in diastolic and mean arterial pressure correlated significantly with the total</strong>
|
|
<hr />
|
|
<strong>
|
|
Intravenous infusion of free fatty acid (FFA) 20 mg.kg-1.min-1 produces pulmonary edema, hypoxemia,
|
|
hyperventilation and increase in the alveolar surfactant content in rabbits in less than 15</strong>
|
|
min.
|
|
</p>
|
|
|
|
<p>
|
|
Respiration 1986;49(3):187-94. <strong>Role of hypocapnia in the alveolar surfactant increase induced by
|
|
free fatty acid intravenous infusion in the rabbit.</strong>
|
|
Oyarzun MJ, Donoso P, Quijada D<strong>. Intravenous infusion of free fatty acid (FFA) produces an increase
|
|
in the alveolar surfactant pool of the rabbit and pulmonary edema, hyperventilation, hypoxemia and
|
|
hypocapnia. Previous studies suggested that alveolar PCO2 would be a regulator of intracellular storages
|
|
of surfactant. In order to</strong>
|
|
<hr />
|
|
</p>
|
|
<p>
|
|
Farmakol Toksikol 1977. Sep-Oct; 40(5):620-3..<strong>
|
|
[Effect of combinations of apressin, obsidan, diprazin, adenosine, NAD and nicotinamide on the
|
|
resistance of rats to hypoxia and on carbohydrate metabolic indices].</strong> [Article in Russian]
|
|
Abakumov GZ As evidenced from experiments on rats, a combined application of apressin with obsidan and
|
|
diprazine, and also of adenozine with nicotine-amidadenine-dinucleotide (NAD), as well as of adeozine with
|
|
nicotine amide potentiates the protective effect of these substances in hypobaric hypoxia, increases the
|
|
resistance of the animals to cerebral ischemia, <strong>brings down the excess lactate level and raises the
|
|
redoz potential of the system lactic-acid-pyruvic</strong> acid in the brain of rats exposed to the
|
|
effects of rarefied atmosphere.
|
|
</p>
|
|
|
|
<p>
|
|
Schweiz Med Wochenschr 1977 Nov 5;107(44):1585-6. <strong>[Protective effect of pyridoxilate on the hypoxic
|
|
myocardium. Experimental studies].</strong> [Article in French] Moret PR, Lutzen U The protective action
|
|
of piridoxilate on hypoxic myocardium has been studied on rats in acute hypoxia (isolated heart, perfused
|
|
with a non-oxygenated solution) and in prolonged hypoxia (3 days at high [3454 m] altitude). Piridoxilate
|
|
maintained a higher ATP level with a much lower production of lactate. <strong>The mechanisms of action of
|
|
piridoxilate are probably fairly similar to those of Na dichloracetate</strong>.
|
|
</p>
|
|
<p>
|
|
J. Appl Physiol 1991 Apr;70(4):1720-30. .<strong>Metabolic and work efficiencies during exercise in Andean
|
|
natives.</strong> Hochachka PW, Stanley C, Matheson GO, McKenzie DC, Allen PS, Parkhouse WS Department
|
|
of Zoology, University of British Columbia, Vancouver, Canada. <strong>
|
|
Maximum O2 and CO2 fluxes during exercise were less perturbed by hypoxia in Quechua natives</strong>
|
|
from the Andes than in lowlanders. In exploring how this was achieved, we found that, <strong>for a given
|
|
work rate, Quechua highlanders at 4,200 m accumulated substantially less lactate
|
|
</strong>than lowlanders at sea level normoxia (approximately 5-7 vs. 10-14 mM) despite hypobaric hypoxia.
|
|
This phenomenon, known as the lactate paradox, was entirely refractory to normoxia-hypoxia transitions. In
|
|
lowlanders, the lactate paradox is an acclimation; however, in Quechuas, the lactate paradox is an
|
|
expression of metabolic organization that did not deacclimate, at least over the 6-wk period of our study.
|
|
Thus it was concluded that this metabolic organization is a developmentally or genetically fixed
|
|
characteristic selected because of the <strong>efficiency advantage of aerobic metabolism (high ATP yield
|
|
per mol of substrate metabolized) compared with anaerobic glycolysis.</strong> Measurements of
|
|
respiratory quotient indicated preferential use of carbohydrate as fuel for muscle work, which is also
|
|
advantageous in hypoxia because it maximizes the yield of ATP per mol of O2 consumed. Finally, minimizing
|
|
the cost of muscle work was also reflected in energetic efficiency as classically defined (power output per
|
|
metabolic power input);<strong>
|
|
this was evident at all work rates but was most pronounced at submaximal work rates (efficiency
|
|
approximately 1.5 times higher than in lowlander athletes).</strong> Because plots of power output vs.
|
|
metabolic power input did not extrapolate to the origin, it was concluded 1) that exercise in both groups
|
|
sustained a significant ATP expenditure not convertible to mechanical work but 2) that this expenditure was
|
|
downregulated in Andean natives by thus far unexplained mechanisms.
|
|
</p>
|
|
|
|
<p>
|
|
Br J Anaesth 1975 Jun;47(6):669-78. <strong>Effect of CO2 on myocardial contractility and aortic input
|
|
impedance during anaesthesia.</strong> Foex P, Prys-Roberts C. The haemodynamic responses to hypocapnia
|
|
and hypercapnia have been studied in the dog during intermittent positive pressure ventilation under
|
|
halothane anaesthesia (1% halothane in oxygen) and under nitrous oxide anaesthesia (30% oxygen in nitrous
|
|
oxide). In the absence of significant<strong>
|
|
variations of either myocardial contractility or left ventricular end-diastolic pressure, the changes of
|
|
stroke volume and cardiac output (diminution because of hypocapnia, augmentation because of hypercapnia)
|
|
were determined by alterations of systemic vascular resistance (augmentation because of hypocapnia,
|
|
diminution because of hypercapnia).
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
J Appl Physiol 1991 May;70(5):1963-76.<strong>
|
|
Skeletal muscle metabolism and work capacity: a 31P-NMR study of Andean natives and lowlanders.</strong>
|
|
Matheson GO, Allen PS, Ellinger DC, Hanstock CC, Gheorghiu D, McKenzie DC, Stanley C, Parkhouse WS,
|
|
Hochachka PW Sports Medicine Division, University of British Columbia, Vancouver, Canada. Two metabolic
|
|
features of altitude-adapted humans are the <strong>maximal O2 consumption (VO2max) paradox (higher work
|
|
rates following acclimatization without increases in VO2max)
|
|
</strong>and the lactate paradox (progressive reductions in muscle and blood lactate with exercise at
|
|
increasing altitude). To
|
|
</p>
|
|
|
|
<p>
|
|
J Hum Hypertens 1995 Feb;9(2):119-22.<strong>
|
|
Pressor effect of hyperventilation in healthy subjects.</strong>Todd GP, Chadwick IG, Yeo WW, Jackson
|
|
PR, Ramsay LE.
|
|
</p>
|
|
<p>
|
|
J Infect Dis 1998 May;177(5):1418-21.<strong>The effect of lactic acid on mononuclear cell secretion of
|
|
proinflammatory cytokines in response to group B streptococci.</strong>
|
|
Steele PM, Augustine NH, Hill HR Department of Pathology, University of Utah School of Medicine, Salt Lake
|
|
City 84132, USA.<strong><hr /></strong>
|
|
</p>
|
|
<p>
|
|
J Appl Physiol 1994 Apr;76(4):1462-7<strong>.</strong> Lactic acidosis as a facilitator of oxyhemoglobin
|
|
dissociation during exercise. Stringer W, Wasserman K, Casaburi R, Porszasz J, Maehara K, French W.
|
|
</p>
|
|
|
|
<p>
|
|
<strong>Involvement of nitric oxide and N-methyl- D-aspartate in acute hypoxic altitude convulsion in mice.
|
|
</strong>Chen CH; Chen AC; Liu HJ. Aviat Space Environ Med, 1997 Apr, 68:4, 296-9. "Altitude convulsion is a
|
|
rather specific form of experimental convulsion which is induced by acute exposure to a hypobaric hypoxic
|
|
condition. Several neurotransmitters have been shown to be involved in the mechanisms of altitude
|
|
convulsions." "The novel neurotransmitter nitric oxide (NO) may be involved in the mechanisms of altitude
|
|
convulsion through its neuronal signalling roles in relation to the NMDA receptor." <strong>"NO synthesis
|
|
precursor, L-arginine (20, 40, 200, 800 mg/kg), resulted in a dose-dependent decrease in the ACT in
|
|
mice, while the NO synthase (NOS) inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME, 1.25, 2.50, 5.00
|
|
mg/kg, i.p.) increased the ACT."</strong>
|
|
"CONCLUSIONS: These findings suggest an important signalling role for nitric oxide and NMDA in the
|
|
development of altitude convulsion and further support the hypothesized relationship between NMDA-receptor
|
|
mediated neurotoxicity and nitric oxide."<strong> </strong>
|
|
</p>
|
|
<p>
|
|
<strong>Excitotoxicity in the lung: N-methyl-D-aspartate- induced, nitric oxide-dependent, pulmonary edema
|
|
is attenuated by vasoactive intestinal peptide and by inhibitors of poly(ADP-ribose) polymerase.
|
|
</strong>
|
|
Said SI; Berisha HI; Pakbaz H. Proc Natl Acad Sci U S A, 1996 May 14, 93:10, 4688-92. <strong>"Excitatory
|
|
amino acid toxicity, resulting from overactivation of N-methyl-D-aspartate (NMDA) glutamate receptors,
|
|
is a major mechanism of neuronal cell death in acute and chronic neurological diseases. We have
|
|
investigated whether excitotoxicity may occur in peripheral organs, causing tissue injury, and report
|
|
that NMDA receptor activation in perfused, ventilated rat lungs triggered acute injury, marked by
|
|
increased pressures needed to ventilate and perfuse the lung, and by high-permeability edema."</strong>
|
|
The injury was prevented by competitive NMDA receptor antagonists or by channel-blocker MK-801, and <strong
|
|
>was reduced in the presence of Mg2+.</strong> As with NMDA toxicity to central neurons, the lung injury was
|
|
nitric oxide (NO) dependent: it <strong>required L-arginine, was associated with increased production of
|
|
NO,</strong> and was attenuated by either of two NO synthase inhibitors. The neuropeptide<strong>
|
|
</strong>vasoactive intestinal peptide and<strong>
|
|
inhibitors of poly(ADP-ribose) polymerase also prevented this injury, but without inhibiting NO
|
|
synthesis, both acting by inhibiting a toxic action of NO that is critical to tissue injury.
|
|
</strong>
|
|
|
|
The findings indicate that: (i) NMDA receptors exist in the lung (and probably elsewhere outside the central
|
|
nervous system), (ii) excessive activation of these receptors may provoke acute edematous lung injury as
|
|
seen in the "adult respiratory distress syndrome," and (iii) this injury can be modulated by blockade of one
|
|
of three critical steps: NMDA receptor binding, inhibition of NO synthesis, or activation of
|
|
poly(ADP-ribose) polymerase.
|
|
</p>
|
|
<p>
|
|
<strong>Adenosine modulates N-methyl-D- aspartate- stimulated hippocampal nitric oxide production in vivo.
|
|
</strong>Bhardwaj A; Northington FJ; Koehler RC; Stiefel T; Hanley DF; Traystman RJ. Stroke, 1995 Sep, 26:9,
|
|
1627-33. "Adenosine acts presynaptically to inhibit release of excitatory amino acids (EAAs) and is thus
|
|
considered to be neuroprotective. Because EAA-stimulated synthesis of nitric oxide (NO) may play an
|
|
important role in long-term potentiation and excitotoxic-mediated injury, we tested the hypotheses that
|
|
adenosine agonists attenuate basal and EAA-induced NO production in the hippocampus in vivo and that
|
|
adenosine A1 receptors mediate this response." "...these data are consistent with in vitro results showing
|
|
that NMDA receptor stimulation enhances NO production. Furthermore, we conclude that stimulation of A1
|
|
receptors can attenuate the basal as well as NMDA-induced production of NO. Because NMDA receptor
|
|
stimulation amplifies glutamate release, our data are consistent with presynaptic A1 receptor-mediated
|
|
inhibition of EAA release and consequent downregulation of NO production."
|
|
</p>
|
|
<p>
|
|
Anesthesiology 1993 Jan;78(1):91-9.<strong>
|
|
Hypocapnia worsens arterial blood oxygenation and increases VA/Q heterogeneity in canine pulmonary
|
|
edema.</strong> Domino KB, Lu Y, Eisenstein BL, Hlastala MP. University of Washington Medical School,
|
|
Seattle. "Hyperventilation frequently is employed to reduce carbon dioxide partial pressure in patients in
|
|
the operating room and intensive care unit. However the effect of hypocapnia on oxygenation is complex and
|
|
may result in worsening in patients with preexisting intrapulmonary shunt." "Both hypocapnia and hypercapnia
|
|
were associated with an increased VA/Q inequality. However, PaO2 decreased and P[A-a]O2 increased with only
|
|
hypocapnia. These results suggest that hyperventilation to reduce PaCO2 may be detrimental to arterial PO2
|
|
in some patients with lung disease."
|
|
</p>
|
|
|
|
<p>
|
|
<strong>Acta Anaesthesiol Scand 1996 Jan;40(1):133-4 Hyperlactatemia associated with hypocarbic
|
|
hyperventilation. Cheung PY</strong>
|
|
</p>
|
|
<p>
|
|
Am J Physiol 1999 May;276(5 Pt 1):E922-9 Hyperlactatemia reduces muscle glucose uptake and GLUT-4 mRNA while
|
|
increasing (E1alpha)PDH gene expression in rat. Lombardi AM, Fabris R, Bassetto F, Serra R, Leturque A,
|
|
Federspil G, Girard J, Vettor R Endocrine Metabolic Laboratory, Department of Medical and Surgical Sciences,
|
|
University of Padova, 35100 Padova, Italy. <strong>
|
|
An increased basal plasma lactate concentration is present in many physiological and pathological
|
|
conditions, including obesity and diabetes. We previously demonstrated that acute lactate infusion in
|
|
rats produced a decrease in overall glucose uptake.</strong>
|
|
The present study was carried out to further investigate the effect of lactate on glucose transport and
|
|
utilization in skeletal muscle. In chronically catheterized rats, a 24-h sodium lactate or bicarbonate
|
|
infusion was performed. To study glucose uptake in muscle, a bolus of 2-deoxy-[3H]glucose was injected in
|
|
basal condition and during euglycemic-hyperinsulinemic clamp. Our results show that hyperlactatemia
|
|
decreased glucose uptake in muscles (i.e., red quadriceps; P < 0.05). Moreover in red muscles, both
|
|
GLUT-4 mRNA (-30% in red quadriceps and -60% in soleus; P < 0.025) and protein (-40% in red quadriceps; P
|
|
< 0.05) were decreased, whereas the (E1alpha)pyruvate dehydrogenase (PDH) mRNA was increased (+40% in red
|
|
quadriceps; P < 0.001) in lactate-infused animals. PDH protein was also increased (4-fold in red
|
|
gastrocnemius and 2-fold in red quadriceps). These results indicate that <strong>chronic
|
|
hyperlactatemia</strong> reduces glucose uptake by affecting the expression of genes involved in glucose
|
|
metabolism in muscle, suggesting a role for lactate in t<strong>he development of insulin
|
|
resistance.</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Radiat Res 1993 Apr;134(1):79-85 <strong>Effects of in vivo heart irradiation on myocardial energy
|
|
metabolism in rats.</strong>
|
|
Franken NA, Hollaar L, Bosker FJ, van Ravels FJ, van der Laarse A, Wondergem J Department of Clinical
|
|
Oncology, University Hospital, Leiden, The Netherlands. To investigate the effect of in vivo heart
|
|
irradiation on myocardial energy metabolism, we measured myocardial adenosine nucleotide concentrations and
|
|
mitochondrial oxygen consumption in left ventricular tissue of rats 0-16 months after local heart
|
|
irradiation (20 Gy). At 24 h and 2 months no difference in myocardial adenosine nucleotide concentration was
|
|
apparent between irradiated and control hearts. The total myocardial adenosine nucleotide concentrations in
|
|
irradiated hearts compared to those of nonirradiated controls tended to be lower from 4 months onward. The
|
|
rate of<strong>
|
|
oxidative energy production (state 3 respiration) in irradiated hearts was significantly reduced ompared
|
|
with that of age-matched controls from 2 months onward. Moreover, as a result of aging, time-dependent
|
|
decrease in the rate of oxidative energy production was observed in both rradiated and control hearts
|
|
</strong>
|
|
<hr />
|
|
<strong>changes in energy supplies provide a mechanism to explain impaired contractility after local heart
|
|
irradiation.
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
J Radiat Res (Tokyo) 1993 Sep;34(3):195-203.<strong>
|
|
Radiosensitization of human lung fibroblasts by chemical that decrease ATP levels.
|
|
</strong>Kumar A, Kimura H, Aoyama T.<strong>
|
|
"Radiosensitization by lactate, pyruvate, nalidixic acid and novobiocin was studied in exponentially
|
|
growing SH-18L human lung fibroblasts. All the chemicals had a slight radiosensitizing effect at a low
|
|
concentration and a definite effect at a higher one." "Fibroblasts incubated with the low concentration
|
|
of each chemical for 24 hrs after X irradiation showed no reduction in intracellular ATP content,
|
|
whereas, the higher concentration produced a significant decrease.
|
|
</strong>These observations suggest that the decrease in the ATP content may be involved in the
|
|
radiosensitization of human fibroblasts at high concentrations of these chemicals.<strong>
|
|
In contrast, radiosensitization at a low concentration is not explained by a relationship to ATP
|
|
content. Different mechanisms may be involved in radiosensitization at low and high concentrations of
|
|
these chemicals."</strong>
|
|
</p>
|
|
<p>
|
|
J Exp Med 1993 May 1;177(5):1391-8. <strong>Enhancement of experimental metastasis by tumor necrosis
|
|
factor.</strong> Orosz P, Echtenacher B, Falk W, Ruschoff J, Weber D, Mannel D.N. Institute for
|
|
Immunology and Genetics, German Cancer Research Center, Heidelberg. "The influence of endogenous and
|
|
exogenous tumor necrosis factor (TNF) on metastasis was investigated in an experimental fibrosarcoma
|
|
metastasis model." "This effect was time dependent, as administration of rmTNF 5 h before or 1 h but not 24
|
|
h after tumor cell inoculation caused an increase of tumor cell colony formation on the lung surface,
|
|
suggesting an influence of TNF on the vascular adhesion and diapedesis of tumor cells. Since tumor-bearing
|
|
mice showed an enhanced ability to produce TNF after endotoxin injection compared to control mice,
|
|
tumor-bearing mice were treated with anti-mTNF antibodies. Neutralization of endogenous tumor-induced TNF
|
|
led to a significant decrease of the number of pulmonary metastases. Histological analysis of
|
|
micrometastases in the lung on day 5 by silver staining of proteins associated with nucleolar organizer
|
|
regions revealed <strong>
|
|
more metastatic foci and augmented proliferative activity of the tumor cells after
|
|
</strong>
|
|
<strong>rmTNF pretreatment of mice.</strong> However, no direct effect of rmTNF on the proliferation rate of
|
|
tumor cells was seen in vitro."
|
|
</p>
|
|
<p>
|
|
Nippon Geka Gakkai Zasshi 1996 Sep;97(9):726-32.<strong>
|
|
[Energy substrate metabolism during stress].
|
|
</strong> Sugimoto H. Department of Traumatology and Critical Care Medicine, Osaka University School of
|
|
Medicine, Suita, Japan.<strong>
|
|
"Energy substrate metabolism during stress is characterized by increased REE (resting energy
|
|
expenditure), hyperglycemia, hyperlactatemia and protein catabolism. This stress-induced hypermetabolic
|
|
responses are closely related to increased secretion of neurohormonal and cytokine mediators. The
|
|
insulin resistance hyperglycemia has been called "stress diabetes" or 'surgical diabetes.' Glucose
|
|
disposal has been thought to be impaired in this condition." "This hyperglycemia in stress diabetes
|
|
results from a postreceptor mechanism. Stress hyperlactatemia is thought to be caused by decreased
|
|
pyruvate dehydrogenase activity rather than tissue hypoperfusion."</strong>
|
|
</p>
|
|
<p>
|
|
<em>Clin Physiol 1995 Nov;15(6):581-95.
|
|
</em>
|
|
<strong><em>Effects of lactate infusion on hepatic gluconeogenesis and glycogenolysis.</em></strong>
|
|
<em>
|
|
Haesler E, Schneiter P, Temler E, Jequier E, Tappy L.</em>
|
|
</p>
|
|
<p>
|
|
<em>Cancer Res 1993 Apr. 15;53(8):1939-44..
|
|
</em>
|
|
<strong><em>Tumor necrosis factor alpha as an autocrine and paracrine growth factor for ovarian cancer:
|
|
monokine induction of tumor cell proliferation and tumor necrosis factor alpha expression.</em
|
|
></strong>
|
|
<em>
|
|
Wu S, Boyer CM, Whitaker RS, Berchuck A, Wiener JR, Weinberg JB, Bast RC Jr.</em>
|
|
</p>
|
|
<p>
|
|
Klin Med (Mosk) 1989 May;67(5):38-41<strong>. ["Dry" carbon dioxide baths in treating patients with
|
|
myocardial infarction at the sanatorium stage of rehabilitation].
|
|
</strong>
|
|
|
|
[Article in Russian] Barashkova NL, Kartamysheva NL, Krasnova VP, Kriuchkova LN, Miasoedova E.S. A group of
|
|
75 patients with a history of myocardial infarction and repeated myocardial infarction were subjected to
|
|
treatment involving dry carbon dioxide baths. Its results demonstrated normalization of IHD manifestations,
|
|
such as coronary and heart failure, functional state of the cardiovascular system, its reserve
|
|
potentialities and adaptation to physical effort. Under the influence of a course treatment with dry carbon
|
|
dioxide baths hemodynamic parameters of cardiac output (cardiac and stroke volume) underwent favourable
|
|
changes, rhythm slowed down, diastole became longer and systolic and diastolic arterial pressure decreased.
|
|
The data obtained substantiate application of dry carbon dioxide baths in the recovery period to I-III
|
|
functional classes patients with a history of myocardial infarction.
|
|
</p>
|
|
<p>
|
|
J Dev Physiol 1989 Nov;12(5):283-6. <strong>Haemodynamic effects of respiratory alkalosis independent of
|
|
changes in airway pressure in anaesthetized newborn dogs.</strong> Reuter JH, Donovan EF, Kotagal U.R.
|
|
<strong>"We have recently reported a decrease in cardiac output in newborn dogs during respiratory alkalosis
|
|
which is independent of changes in airway pressure."</strong>
|
|
</p>
|
|
<p>
|
|
Undersea Hyperb Med 1994 Jun;21(2):169-83. <strong>Influence of hyperbaric oxygen on left ventricular
|
|
contractility, total coronary blood flow, and myocardial oxygen consumption in the conscious dog.
|
|
</strong>
|
|
Savitt MA, Rankin JS, Elberry JR, Owen CH, Camporesi E.M. <strong>"It is known that hyperbaric oxygenation
|
|
(HBO) decreases total coronary blood flow (TCBF) and cardiac output (CO)."</strong>
|
|
</p>
|
|
<p>
|
|
<strong><em>Heart rhythm disturbances in the inhabitants of mountainous regions.</em></strong>
|
|
<em>
|
|
Mirrakhimov MM; Meimanaliev TS Cor Vasa, 1981, 23:5, 359-65.
|
|
</em>
|
|
<strong><em>"During exercise heart arrhythmias</em></strong>
|
|
<strong><em>
|
|
appeared conspicuously less frequently in the high mountain than in the low altitude inhabitants."
|
|
</em></strong>
|
|
</p>
|
|
<p>© Ray Peat 2006. All Rights Reserved. www.RayPeat.com</p>
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