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djledda-web/raypeat-articles/processed/protective-co2-aging.html

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  1. <html>

  2.     <head><title></title></head>

  3.     <body>

  4.         <h1></h1>

  5. 

  6.         <p>

  7.             <strong>Protective CO2 and aging</strong>

  8.         </p>The therapeutic effects of increasing carbon dioxide are being more widely recognized in recent years. Even

  9.         Jane Brody, the NY Times writer on health topics, has favorably mentioned the use of the Buteyko method for

  10.         asthma, and the idea of "permissive hypercapnia" during mechanical ventilation, to prevent lung damage from

  11.         excess oxygen, has been discussed in medical journals. But still very few biologists recognize its role as a

  12.         fundamental, universal protective factor. I think it will be helpful to consider some of the ways carbon dioxide

  13.         might be controlling situations that otherwise are poorly understood. The brain has a high rate of oxidative

  14.         metabolism, and so it forms a very large proportion of the carbon dioxide produced by an organism. It also

  15.         governs, to a great extent, the metabolism of other tissues, including their consumption of oxygen and

  16.         production of carbon dioxide or lactic acid. Within a particular species, the rate of oxygen consumption

  17.         increases in proportion to brain size, rather than body weight. Between very different species, the role of the

  18.         brain in metabolism is even more obvious, since the resting metabolic rate corresponds to the size of the brain.

  19.         For example, a cat"s brain is about the size of a crocodile"s, and their oxygen consumption at rest is similar,

  20.         despite their tremendous difference in body size.Stress has to be understood as a process that develops in time,

  21.         and the brain (especially the neocortex and the frontal lobes) organizes the adaptive and developmental

  22.         processes in both the spatial and temporal dimensions. The meaning of a situation influences the way the

  23.         organism responds. For example, the stress of being restrained for a long time can cause major gastrointestinal

  24.         bleeding and ulcerization, but if the animal has the opportunity to bite something during the stress (signifying

  25.         its ability to fight back, and the possibility of escape) it can avoid the stress ulcers. The patterning of the

  26.         nervous activity throughout the body governs the local ability to produce carbon dioxide. When the cortex of the

  27.         brain is damaged or removed, an animal becomes rigid, so the cortex is considered to have a "tonic inhibitory

  28.         action" on the body. But when the nerves are removed from a muscle (for example, by disease or accident), the

  29.         muscle goes into a state of constant activity, and its ability to oxidize glucose and produce carbon dioxide is

  30.         reduced, while its oxidation of fatty acids persists, increasing the production of toxic oxidative fragments of

  31.         the fatty acids, which contributes to the muscle"s atrophy.The organism"s intentions, expectations, or plans,

  32.         are represented in the nervous system as a greater readiness for action, and in the organs and tissues

  33.         controlled by the nerves, as an increase or decrease of oxidative efficiency, analogous to the differences

  34.         between innervated and denervated muscles. This pattern in the nervous system has been called "the acceptor of

  35.         action," because it is continually being compared with the actual situation, and being refined as the situation

  36.         is evaluated. The state of the organism, under the influence of a particular acceptor of action, is called a

  37.         "functional system," including all the components of the organism that participate most directly in realizing

  38.         the intended adaptive action.The actions of nerves can be considered anabolic, because during a stressful

  39.         situation in which the catabolic hormones of adaption, e.g., cortisol, increase, the tissues of the functional

  40.         system are protected, and while idle tissues may undergo autophagy or other form of involution, the needs of the

  41.         active tissues are supplied with nutrients from their breakdown, allowing them to change and, when necessary,

  42.         grow in size or complexity. The brain"s role in protecting against injury by stress, when it sees a course of

  43.         action, has a parallel in the differences between concentric (positive, muscle shortening) and eccentric

  44.         (negative, lengthening under tension) exercise, and also with the differences between innervated and denervated

  45.         muscles. In eccentric exercise and denervation, less oxygen is used and less carbon dioxide is produced, while

  46.         lactic acid increases, displacing carbon dioxide, and more fat is oxidized. Prolonged stress similarly decreases

  47.         carbon dioxide and increases lactate, while increasing the use of fat.Darkness is stressful and catabolic. For

  48.         example, in aging people, the morning urine contains nearly all of the calcium lost during the 24 hour period,

  49.         and mitochondria are especially sensitive to the destructive effects of darkness. Sleep reduces the destructive

  50.         catabolic effects of darkness. During the rapid-eye-movement (dreaming) phase of sleep, breathing is inhibited,

  51.         and the level of carbon dioxide in the tissues accumulates. In restful sleep, the oxygen tension is frequently

  52.         low enough, and the carbon dioxide tension high enough, to trigger the multiplication of stem cells and

  53.         mitochondria.Dreams represent the "acceptor of action" operating independently of the sensory information that

  54.         it normally interacts with. During dreams, the brain (using a system called the Ascending Reticular Activating

  55.         System) disconnects itself from the sensory systems. I think this is the nervous equivalent of

  56.         concentric/positive muscle activity, in the sense that the brain is in control of its actions. The active,

  57.         dreaming phase of sleep occurs more frequently in the later part of the night, as morning approaches. This is

  58.         the more stressful part of the night, with cortisol and some other stress hormones reaching a peak at dawn, so

  59.         it would be reasonable for the brain"s defensive processes to be most active at that time. The dreaming process

  60.         in the brain is associated with deep muscle relaxation, which is probably associated with the trophic

  61.         (restorative) actions of the nerves.In ancient China the Taoists were concerned with longevity, and according to

  62.         Joseph Needham (<em>Science and Civilization in China</em>) their methods included the use of herbs, minerals,

  63.         and steroids extracted from the urine of children. Some of those who claimed extreme longevity practiced

  64.         controlled breathing and tai chi (involving imagery, movement, and breating), typically in the early morning

  65.         hours, when stress reduction is most important. As far as I know, there are no studies of carbon dioxide levels

  66.         in practitioners of tai chi, but the sensation of warmth they typically report suggests that it involves

  67.         hypoventilation.In the 1960s, a Russian researcher examined hospital records of measurements of newborn babies,

  68.         and found that for several decades the size of their heads had been increasing. He suggested that it might be

  69.         the result of increasing atmospheric carbon dioxide. The experiences and nutrition of a pregnant animal are

  70.         known to affect the expression of genes in the offspring, affecting such things as allergies, metabolic rate,

  71.         brain size, and intelligence. Miles Storfer (1999) has reviewed the evidence for epigenetic environmental

  72.         control of brain size and intelligence. The main mechanisms of epigenetic effects or "imprinting" are now known

  73.         to involve methylation and acetylation of the chromosomes (DNA and histones).Certain kinds of behavior, as well

  74.         as nutrition and other environmental factors, increase the production and retention of carbon dioxide. The

  75.         normal intrauterine level of carbon dioxide is high, and it can be increased or decreased by changes in the

  76.         mother"s physiology. The effects of carbon dioxide on many biological processes involving methylation and

  77.         acetylation of the genetic material suggest that the concentration of carbon dioxide during gestation might

  78.         regulate the degree to which parental imprinting will persist in the developing fetus. There is some evidence of

  79.         increased demethylation associated with the low level of oxygen in the uterus (Wellman, et al., 2008). A high

  80.         metabolic rate and production of carbon dioxide would increase the adaptability of the new organism, by

  81.         decreasing the limiting genetic imprints.A quick reduction of carbon dioxide caused by hyperventilation can

  82.         provoke an epileptic seizure, and can increase muscle spasms and vascular leakiness, and (by releasing serotonin

  83.         and histamine) contribute to inflammation and clotting disorders. On a slightly longer time scale, a reduction

  84.         of carbon dioxide can increase the production of lactic acid, which is a promoter of inflammation and fibrosis.

  85.         A prolonged decrease in carbon dioxide can increase the susceptibility of proteins to glycation (the addition of

  86.         aldehydes, from polyunsaturated fat peroxidation or methylglyoxal from lactate metabolism, to amino groups), and

  87.         a similar process is likely to contribute to the methylation of histones, a process that increases with aging.

  88.         Histones regulate genetic activity.With aging, DNA methylation is increased (Bork, et al., 2009). <strong>I

  89.             suggest that methylation stabilizes and protects cells when growth and regeneration aren"t possible (and

  90.             that it"s likely to increase when CO2 isn"t available).

  91.         </strong>Hibernation (Morin and Storey, 2009) and sporulation (Ruiz-Herrera, 1994; Clancy, et al., 2002) appear

  92.         to use methylation protectively.Parental stress, prenatal stress, early life stress, and even stress in

  93.         adulthood contribute to "imprinting of the genes," partly through methylation of DNA and the histones.

  94.         Methionine and choline are the main dietary sources of methyl donors. Restriction of methionine has many

  95.         protective effects, including increased average (42%) and maximum (44%) longevity in rats (Richie, et al.,

  96.         1994). Restriction of methyl donors causes demethylation of DNA (Epner, 2001). <strong></strong>The age

  97.         accelerating effect of methionine might be related to disturbing the methylation balance, inappropriately

  98.         suppressing cellular activity. Besides its effect on the methyl pool, methionine inhibits thyroid function and

  99.         damages mitochondria. The local concentration of carbon dioxide in specific tissues and organs can be adjusted

  100.         by nervous and hormonal activation or inhibition of the carbonic anhydrase enzymes, that accelerate the

  101.         oonversion of CO2 to carbonic acid, H2CO3. The activity of carbonic anhydrase can determine the density and

  102.         strength of the skeleton, the excitability of nerves, the accumulation of water, and can regulate the structure

  103.         and function of the tissues and organs. Ordinarily, carbon dioxide and bicarbonate are thought of only in

  104.         relation to the regulation of pH, and only in a very general way. Because of the importance of keeping the pH of

  105.         the blood within a narrow range, carbon dioxide is commonly thought of as a toxin, because an excess can cause

  106.         unconsciousness and acidosis. But increasing carbon dioxide doesn"t necessarily cause acidosis, and acidosis

  107.         caused by carbon dioxide isn"t as harmful as lactic acidosis.Frogs and toads, being amphibians, are especially

  108.         dependent on water, and in deserts or areas with a dry season they can survive a prolonged dry period by

  109.         burrowing into mud or sand. Since they may be buried 10 or 11 inches below the surface, they are rarely found,

  110.         and so haven"t been extensively studied. In species that live in the California desert, they have been known to

  111.         survive 5 years of burial without rainfall, despite a moderately warm average temperature of their surroundings.

  112.         One of their known adaptations is to produce a high level of urea, allowing them to osmotically absorb and

  113.         retain water. (Very old people sometimes have extremely high urea and osmotic tension.)Some laboratory studies

  114.         show that as a toad burrows into mud, the amount of carbon dioxide in its tissues increases. Their skin normally

  115.         functions like a lung, exchanging oxygen for carbon dioxide. If the toad"s nostrils are at the surface of the

  116.         mud, as dormancy begins its breathing will gradually slow, increasing the carbon dioxide even more. Despite the

  117.         increasing carbon dioxide, the pH is kept stable by an increase of bicarbonate (Boutilier, et al., 1979). A

  118.         similar increase of bicarbonate has been observed in hibernating hamsters and doormice.Thinking about the long

  119.         dormancy of frogs reminded me of a newspaper story I read in the 1950s. Workers breaking up an old concrete

  120.         structure found a dormant toad enclosed in the concrete, and it revived soon after being released. The concrete

  121.         had been poured decades earlier. Although systematic study of frogs or toads during their natural buried

  122.         estivation has been very limited, there have been many reports of accidental discoveries that suggest that the

  123.         dormant state might be extended indefinitely if conditions are favorable. Carbon dioxide has antioxidant

  124.         effects, and many other stabilizing actions, including protection against hypoxia and the excitatory effects of

  125.         intracellular calcium and inflammation (Baev, et al., 1978, 1995; Bari, et al., 1996; Brzecka, 2007; Kogan, et

  126.         al., 1994; Malyshev, et al., 1995).When mitochondria are "uncoupled," they produce more carbon dioxide than

  127.         normal, and the mitochondria produce fewer free radicals. Animals with uncoupled mitochondria live longer than

  128.         animals with the ordinary, more efficient mitochondria, that produce more reactive oxidative fragments. One

  129.         effect of the high rate of oxidation of the uncoupled mitochondria is that they can eliminate polyunsatured

  130.         fatty acids that might otherwise be integrated into tissue structures, or function as inappropriate regulatory

  131.         signals.Birds have a higher metabolic rate than mammals of the same size, and live longer. Their tissues contain

  132.         fewer of the highly unsaturated fatty acids. Queen bees, which live many times longer than worker bees, have

  133.         mainly monounsaturated fats in their tissues, while the tissues of the short-lived worker bees, receiving a

  134.         different diet, within a couple of weeks of hatching will contain highly unsaturated fats.Bats have a very high

  135.         metabolic rate, and an extremely long lifespan for an animal of their size. While most animals of their small

  136.         size live only a few years, many bats live a few decades. Bat caves usually have slightly more carbon dioxide

  137.         than the outside atmosphere, but they usually contain a large amount of ammonia, and bats maintain a high serum

  138.         level of carbon dioxide, which protects them from the otherwise toxic effects of the ammonia. The naked mole

  139.         rat, another small animal with an extremely long lifespan (in captivity they have lived up to 30 years, 9 or 10

  140.         times longer than mice of the same size) has a low basal metabolic rate, but I think measurements made in

  141.         laboratories might not represent their metabolic rate in their natural habitat. They live in burrows that are

  142.         kept closed, so the percentage of oxygen is lower than in the outside air, and the percentage of carbon dioxide

  143.         ranges from 0.2% to 5% (atmospheric CO2 is about 0.038). The temperature and humidity in their burrows can be

  144.         extremely high, and to be very meaningful their metabolic rate would have to be measured when their body

  145.         temperature is raised by the heat in the burrow.When they have been studied in Europe and the US, there has been

  146.         no investigation of the effect of altitude on their metabolism, and these animals are native to the high plains

  147.         of Kenya and Ethiopia, where the low atmospheric pressure would be likely to increase the level of carbon

  148.         dioxide in their tissues. Consequently, I doubt that the longevity seen in laboratory situations accurately

  149.         reflects the longevity of the animals in their normal habitat.Besides living in a closed space with a high

  150.         carbon dioxide content, mole rats have another similarity to bees. In each colony, there is only one female that

  151.         reproduces, the queen, and, like a queen bee, she is the largest individual in the colony. In beehives, the

  152.         workers carefully regulate the carbon dioxide concentration, which varies from about 0.2% to 6%, similar to that

  153.         of the mole rat colony. A high carbon dioxide content activates the ovaries of a queen bee, increasing her

  154.         fertility.Since queen bees and mole rats live in the dark, I think their high carbon dioxide compensates for the

  155.         lack of light. (Both light and CO2 help to maintain oxidative metabolism and inhibit lactic acid formation.)

  156.         Mole rats are believed to sleep very little. During the night, normal people tolerate more CO2, and so breathe

  157.         less, especially near morning, with increased active dreaming sleep. A mole rat has never been known to develop

  158.         cancer. Their serum C-reactive protein is extremely low, indicating that they are resistant to inflammation. In

  159.         humans and other animals that are susceptible to cancer, one of the genes that is likely to be silenced by

  160.         stress, aging, and methylation is p53, a tumor-suppressor gene. If the intrauterine experience, with low oxygen

  161.         and high carbon dioxide, serves to "reprogram" cells to remove the accumulated effects of age and stress, and so

  162.         to maximize the developmental potential of the new organism, a life that"s lived with nearly those levels of

  163.         oxygen and carbon dioxide might be able to avoid the progressive silencing of genes and loss of function that

  164.         cause aging and degenerative diseases.Several diseases and syndromes are now thought to involve abnormal

  165.         methylation of genes. Prader-Willi sydrome, Angelman"s syndrome, and various "autistic spectrum disorders," as

  166.         well as post-traumatic stress disorder and several kinds of cancer seem to involve excess methylation. Moderate

  167.         methionine restriction (for example, using gelatin regularly in the diet) might be practical, but if increased

  168.         carbon dioxide can activate the demethylase enzymes in a controlled way, it might be a useful treatment for the

  169.         degenerative diseases and for aging itself. The low carbon dioxide production of hypothyroidism (e.g., Lee and

  170.         Levine, 1999), and the respiratory alkalosis of estrogen excess, are often overlooked. An adequate supply of

  171.         calcium, and sometimes supplementation of salt and baking soda, can increase the tissue content of CO2.<span

  172.             style="white-space: pre-wrap"

  173.         >

  174.         </span>

  175.         <h3>REFERENCES</h3>Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E621-7. <strong>Uncoupling protein-2 regulates

  176.             lifespan in mice.</strong> Andrews ZB, Horvath TL. Fiziol Zh SSSR 1978 Oct;64(10):1456-62. <strong>[Role of

  177.             CO2 fixation in increasing the body's resistance to acute hypoxia].</strong> Baev VI, Vasil'ev VV, Nikolaeva

  178.         EN. In rats, the phenomenon of considerable increase in resistance to acute hypoxia observed after 2-hour stay

  179.         under conditions of gradually increasing concentration of CO2, decreasing concentration of O2, and external

  180.         cooling at 2--3 degrees seems to be based mainly on changes in concentration of CO2 (ACCORDINGLY, PCO2 and other

  181.         forms of CO2 in the blood). The high resistance to acute hypoxia develops as well after subcutaneous or i.v.

  182.         administration of 1.0 ml of water solution (169.2 mg/200 g) NaHCO2, (NH4)2SO4, MgSO4, MnSO4, and ZnSO4 (in

  183.         proportion: 35 : 5 : 2 : 0.15 : 0.15, resp.) or after 1-hour effect of increased hypercapnia and hypoxia without

  184.         cooling. Fiziol Zh Im I M Sechenova 1995 Feb;81(2):47-52.<strong>

  185.             [The unknown physiological role of carbon dioxide].</strong> Baev VI, Vasil'eva IV, L'vov SN, Shugalei IV

  186.         [The data suggests that carbon dioxide is a natural element of the organism antioxidant defence system. ion

  187.         poisoning].Stroke. 1996 Sep;27(9):1634-9; discussion 1639-40. <strong>Differential effects of short-term hypoxia

  188.             and hypercapnia on N-methyl-D-aspartate-induced cerebral vasodilatation in piglets.</strong> Bari F, Errico

  189.         RA, Louis TM, Busija DW.Vojnosanit Pregl. 1996 Jul-Aug;53(4):261-74. <strong>[Carbon dioxide inhibits the

  190.             generation of active forms of oxygen in human and animal cells and the significance of the phenomenon in

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  193.             The effects of burrowing.

  194.         </strong>Boutilier RG, Randall DJ, Shelton G, Toews DP.Acta Neurobiol Exp (Wars). 2007;67(2):197-206. <strong

  195.         >Role of hypercapnia in brain oxygenation in sleep-disordered breathing.</strong> Brzecka A. Adaptive mechanisms

  196.         may diminish the detrimental effects of recurrent nocturnal hypoxia in obstructive sleep apnea (OSA). The

  197.         potential role of elevated carbon dioxide (CO2) in improving brain oxygenation in the patients with severe OSA

  198.         syndrome is discussed. CO2 increases oxygen uptake by its influence on the regulation of alveolar ventilation

  199.         and ventilation-perfusion matching, facilitates oxygen delivery to the tissues by changing the affinity of

  200.         oxygen to hemoglobin, and increases cerebral blood flow by effects on arterial blood pressure and on cerebral

  201.         vessels. Recent clinical studies show improved brain oxygenation when hypoxia is combined with hypercapnia.

  202.         Anti-inflammatory and protective against organ injury properties of CO2 may also have therapeutic importance.

  203.         These biological effects of hypercapnia may improve brain oxygenation under hypoxic conditions. This may be

  204.         especially important in patients with severe OSA syndrome.Ageing Res Rev. 2009 Oct;8(4):268-76. Epub 2009 Apr 1.

  205.         <strong>The role of epigenetics in aging and age-related diseases.</strong> Calvanese V, Lara E, Kahn A, Fraga

  206.         MF.Rev Esp Geriatr Gerontol. 2009 Jul-Aug;44(4):194-9. Epub 2009 Jul 3. <strong>[Effect of restricting amino

  207.             acids except methionine on mitochondrial oxidative stress.]

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  209.         Jan;5(1):21-33. <strong>A central thermogenic-like mechanism in feeding regulation: an interplay between arcuate

  210.             nucleus T3 and UCP2.</strong> Coppola A, Liu ZW, Andrews ZB, Paradis E, Roy MC, Friedman JM, Ricquier D,

  211.         Richard D, Horvath TL, Gao XB, Diano S.Ter Arkh. 1995;67(3):23-6. <strong>[Changes in the sensitivity of

  212.             leukocytes to the inhibiting effect of CO2 on their generation of active forms of oxygen in bronchial asthma

  213.             patients]</strong> Daniliak IG, Kogan AKh, Sumarokov AV, Bolevich S.Cell Metab. 2007 Dec;6(6):497-505.

  214.         <strong>Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease.</strong>

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  217.             Fibrotic Appearance of Lungs in Severe Hypothyroidism is Reversible with Thyroxine Replacement.</strong>

  218.         George JT, Thow JC, Rodger KA, Mannion R, Jayagopal V.J Bioenerg Biomembr. 2009 Jun;41(3):309-21. Epub 2009 Jul

  219.         25. <strong>Effect of methionine dietary supplementation on mitochondrial oxygen radical generation and

  220.             oxidative DNA damage in rat liver and heart.

  221.         </strong>Gomez J, Caro P, Sanchez I, Naudi A, Jove M, Portero-Otin M, Lopez-Torres M, Pamplona R, Barja G.Proc

  222.         Natl Acad Sci U S A. 1996 Jul 23;93(15):7612-7. <strong>Increased tricarboxylic acid cycle flux in rat brain

  223.             during forepaw stimulation detected with 1H[13C]NMR.

  224.         </strong>Hyder F, Chase JR, Behar KL, Mason GF, Siddeek M, Rothman DL, Shulman RG.Can J Neurol Sci. 1979

  225.         May;6(2):105-12. <strong>The effects of partial chronic denervation on forearm metabolism.</strong> Karpati G,

  226.         Klassen G, Tanser P.Biull Eksp Biol Med. 1994 Oct;118(10):395-8. <strong>[CO2--a natural inhibitor of active

  227.             oxygen form generation by phagocytes]</strong> Kogan AKh, Manuilov BM, Grachev SV, Bolevich S, Tsypin AB,

  228.         Daniliak IG.Izv Akad Nauk Ser Biol. 1997 Mar-Apr;(2):204-17.<strong>

  229.             [Carbon dioxide--a universal inhibitor of the generation of active oxygen forms by cells (deciphering one

  230.             enigma of evolution)]

  231.         </strong>Kogan AKh, Grachev SV, Eliseeva SV, Bolevich S.Vopr Med Khim. 1996 Jul-Sep;42(3):193-202.<strong>

  232.             [Ability of carbon dioxide to inhibit generation of superoxide anion radical in cells and its biomedical

  233.             role]</strong> Kogan AKh, Grachev SV, Eliseeva SV, Bolevich S.Dokl Akad Nauk. 1996 May;348(3):413-6. <strong

  234.         >[New evidence for the inhibitory action of CO2 on generation of superoxide anion radicals by phagocytes in

  235.             various tissues. (Mechanism of bio- and eco-effects of CO2)]

  236.         </strong>Kogan AKh, Grachev SV, Bolevich S, Eliseeva SV.Biull Eksp Biol Med. 1996 Apr;121(4):407-10. <strong

  237.         >[Carbon dioxide gas inhibition of active forms of oxygen generation by cells in the internal organs and its

  238.             biological significance]</strong> Kogan AKh, Grachev SV, Eliseeva SV.Fiziol Cheloveka. 1995

  239.         Jul-Aug;21(4):128-36. <strong>[CO2--a natural inhibitor of the generation of active species of oxygen in

  240.             phagocytes]</strong> Kogan AKh, Manuilov BM, Grachev SV, Bolevich S, Tsypin AB, Daniliak IG.<strong>Patol

  241.             Fiziol Eksp Ter. 1995 Jul-Sep;(3):34-40. [Comparative study of the effect of carbon dioxide on the

  242.             generation of active forms of oxygen by leukocytes in health and in bronchial asthma]</strong> Kogan AKh,

  243.         Bolevich S, Daniliak IG.Can J Anaesth. 1999 Feb;46(2):185-9. <strong>Acute respiratory alkalosis associated with

  244.             low minute ventilation in a patient with severe hypothyroidism.</strong> Lee HT, Levine M.Tl128@columbia.edu

  245.         PURPOSE: Patients with severe hypothyroidism present unique challenges to anesthesiologists and demonstrate much

  246.         increased perioperative risks. Overall, they display increased sensitivity to anesthetics, higher incidence of

  247.         perioperative cardiovascular morbidity, increased risks for postoperative ventilatory failure and other

  248.         physiological derangements. The previously described physiological basis for the increased incidence of

  249.         postoperative ventilatory failure in hypothyroid patients includes decreased central and peripheral ventilatory

  250.         responses to hypercarbia and hypoxia, muscle weakness, depressed central respiratory drive, and resultant

  251.         alveolar hypoventilation. These ventilatory failures are associated most frequently with severe hypoxia and

  252.         carbon dioxide (CO2) retention. The purpose of this clinical report is to discuss an interesting and unique

  253.         anesthetic presentation of a patient with severe hypothyroidism. CLINICAL FEATURES: We describe an unique

  254.         presentation of ventilatory failure in a 58 yr old man with severe hypothyroidism. He had exceedingly low

  255.         perioperative respiratory rate (3-4 bpm) and minute ventilation volume, and at the same time developed primary

  256.         acute respiratory alkalosis and associated hypocarbia (P(ET)CO2 approximately 320-22 mmHg). CONCLUSION: Our

  257.         patient's ventilatory failure was based on unacceptably low minute ventilation and respiratory rate that was

  258.         unable to sustain adequate oxygenation. His profoundly lowered basal metabolic rate and decreased CO2

  259.         production, resulting probably from severe hypothyroidism, may have resulted in development of acute respiratory

  260.         alkalosis in spite of concurrently diminished minute ventilation.Anal Bioanal Chem. 2008 Jan;390(2):679-88. Epub

  261.         2007 Oct 27. <strong>The structural modification of DNA nucleosides by nonenzymatic glycation: an in vitro study

  262.             based on the reactions of glyoxal and methylglyoxal with 2'-deoxyguanosine.</strong> Li Y, Cohenford MA,

  263.         Dutta U, Dain JA.Biull Eksp Biol Med. 1995 Jun;119(6):590-3. <strong>[Adaptation to high altitude hypoxia

  264.             facilitates a limitation of lipid peroxidation activation in inflammation and stress] [Article in

  265.             Russian]</strong>Malyshev VV, Vasil'eva LS, Belogorov SB, Nefedova TV.Am J Physiol Regul Integr Comp

  266.         Physiol. 2007 Sep;293(3):R1159-68. Epub 2007 Jun 20.<strong>Denervation-induced skeletal muscle atrophy is

  267.             associated with increased mitochondrial ROS production.</strong> Muller FL, Song W, Jang YC, Liu Y, Sabia M,

  268.         Richardson A, Van Remmen H.Radiobiologiia. 1984 Jan-Feb;24(1):29-34. <strong>[Enzyme activity of glutamic acid

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  322.         Wu H, Sun YI<p>

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