A Ray Peat newsletter.

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>JJI.-v\ d'vl..-v-I/£Nl C.£ l( JLJ JmJ drtt0Jt °ouv MeIk Ray Peat's Newsletter- Not for republication without written permission. P.O. Box 5764, Eugene, OR 97405 Copyright Ray Peat 1991'

k 5 tNn/l.. .M.1JJ, S {1,v(" " (J<4 \ rrY!<.//- 'r ,', ;::4 v( -UYli'Y;X/ Recharging the System, use at least a quart of milk and a quart of orange juice daily, well salted chicken broth, and frequent Adelle Davis wrote about the importance of . increased salt intake in adrenal failure, and animal experimenters have that with ade-quate sodium and sugar, animals can function nor- .,-,<01.1;,: withollt their adrenals. Hans Selye demonstrated that progesterone i-,,"'...; animals healthy for their entire life after their adrenals have been removed. Among its many ef-fects, progesterone regulates the levels of sodium and glucose.

Progesterone is both an antistress hormone .and an antishock hormone; shock is the state that snacks, especially salty foods. I have written be-fore about the importance of fiuit and protein in balancing the hormones, and how adequate energy prevents stress, but I haven't talked about sodium's . central biological role in sustaining our energy, ::::': mp.chanisms behind these effects of diet and hormones..

Shock is the most extreme stress-state there is, and it can shift gradually into death, as energy pro-duction ceases. Things that can bring an individual out of shock are so intimately contlected with our energy production that we should understand how to use them routinely.

In shock, G. W. Crne showed that many sys-tems, ranging from the molecular level to the nerv-ous level, are involved, and he introduced methods ofanesthesia that reduced shock. He imagined the organism--and each cell--as something like an electrical battery: The liver and the brain formed the poles ofthe organism-battery, and the nucleus and cytoplasm fOIll).ed the cell's ".poles." Exhaus-tion and shock, he believed, in some way "dis-charged" the organism's energy, causing changes in every cell. occurs when our defenses are down, and stress is ;"e.-t '2 l;t+l", on thp. "f . -_...: J • • _ • -_ ... a ....._."""'"', -.1.1_ neither will occur when our resources are ade-quate. In any bad biological estrogen is likely to accumulate, interfering with energy pro-duction, causing blood to pool in the legs, causing water retention and sodium loss.

Thyroid, progesterone, protein, and salt are powerful defenses against all sorts of stress-associated symptoms, including hot flashes, insom-nia, cramps, PMS, edema, toxemia of pregnancy, low-birth-weight babies, epilepsy, heart diseases, I suspect that Crile's work on the physiology hypertension, strokes, migraine, inflammatory dis-of excitement, exhaustion, arid shock made Hans eases, hypoglycemia, fatigue and depression. The Selye's work on stress and adaptation "less unac-first approach to an appropriate diet would be to ceptable" to the scientific establishment' than it C;f1oct -Itlvtt!1urtY\. /Ylv. {Vi pOJy tvu.,d-v-S hlJ<-..l ( .so Oiu Wt IG Iv to'Hj II- rp .,(/V)jecf0/PJ ul1/c;g-o /)??<.Jr(lt?//v..... . Nt/1/c would have been without Crile's disturbing prece-dent. Crile warned about the shock-promoting ac-tion of morphine, and influenced the way surgery . was done, bl:1t unfortunately shock is still too often thought of in a mechanical way, as something that happens to the circulatory system, and the various subsequent discoveries about treating shock have seemed too mysterious or too implausible to gain general acceptance. In the absence of a unifying picture of the organism, treatments are likely to be evaluated in terms of a fragmented aspect of the organism, and if they don't mechanically fit into that system in an obvious way, they are dismissed.

I have written previously about several dra-matically effective treatments for shock that were developed in the last fifty years--for example, in-travenous ATP, concentrated solutions of sodium cWoride or glucose, and the morphine/endorphin-blocker, naloxone. Theoretical reasons have kept some of these techniques from being used as widely as would be appropriate, but gradually the success of the methods is forcing some people to rethink their theories.

A simple newer view of the organism's ,energy is being deve10ped, and early acceptance of this new view will make it possible to approach treat-ment in a way that is both integrated and specific.

Although Crne and Selye were famous for their studies of the acute effects of noxious condi-tions, both were interested in the long-term, cumu-lative effects. Crne was more explicit about the general evolutionary implications of his discoveries.

One of the least scientific aspects of conventi-ional "evolutionary thinfing" js the thought that jf an organism has or does something, that thing_or behavior must have "survival value." People apply evolutionary explanations in a carefree way, feel-ing that an explanation without support is better than leaving something unexplained.

Shock, inflammation, aging and death have been proposed to "have survival value," be-cause of this totalitarian view of genetics. Couldn't it be that organisms simply aren't perfect, and that some things are just systematically screwed up? That is, an organism has a certain strength, resistance, or adaptive capacity, but if it finds itself in conditions that are too difficult, then processes that never did anything to aid survival might develop, as several individually valid defen-sive maneuvers 'start to interfere with each other. "Advance" and "retreat," eat and expel, for exam-ple, are- processes that have to be functionally separated; if coordination is lost, new but con-fused processes'WIll emerge. On the cellular level, excitotoxicity -is an example of the loss of coordination.

In1950 Selye, and in 1953, Rees, pointed out the similarities of estrogen's effects to the physiol-ogy of stress and shock. Hundreds of studies'have . confirmed the details of estrogen's actions on the circulatory system, respiration, and metabolism. Since we have the genes needed for making estro-gen, it might seem that there is reason to argue that shock "has a genetic basis," but the mistake occurs when that phraseology is extended to claim that "genes for (something which produces) shock prove that shock has survival value." Estr.ogen's survival value exists only in the context ofa whole organism with multiple ways for limiting estrogen's destabilizing actions. Estrogen's harmful effects o<::cur when our systems for opposing it fail.

Recently, fhere has been a disp.ute...abG1:lbthe reason for the of menstruation among prjrnates. The argument began when Margie Pro-fet proposed that it is an anti-infective defense mechanism, a "cleansing" procedurp. Culturally, this strikes me as primarily a reaction against the archaic doctrine of the "unclean" menses, and sci-entifically, it is hard to imagine that opening blood vessels and bathing the membranes in blood would be an a,nti-infective strategy; in fact, infec,!ions such as gonorrhea and cWamydia are more likely to occur after menstruation, and blood is an' ex-ceedingly good growth medium for gerrits. Her response to that observation was that the preva-lence of diseases such as AIDS, cholera, and tu-berculosis "doesn't mean that the immune system didn't evolve to fight pathogens." I think she is wrong on both issues, the reason for evolving menstruation and the reason for evolving our im-mune system.* If we can see menstruation as a side effect of the adaptations we have for producing large brains, without its own special "menstruation genes," we should also be able to see a phenome-non such as shock as something which is not bio-logically so useful that we "evolved" it in the sense of selecting for "shock genes." (Stumbling is a consequence of walking, and the biological point of interest is the walking, not the stumbling; any interest that stumbling has, is as a "boundary" of the ability to walk.)

My point is to suggest that shock is simply'"a negative thing, a failure of protective systems, a biological screw-up resulting from the same sort of inadequacy of resources that produces "excltotox-icity." The fact that shock-like features can -be seen in the hormonal effects of estrogen, and in the "normal" process of aging, leads to the thought that the body which can control the ef-fects of estrogen should also be able to control the shock reaction and the aging process, ifgiven the appropriate kinds of support. Estrogen cre-ates a bias toward cellular "excitotoxicity,i, since it promotes excitation while limiting energy"produc-t-iOri Our boayc-ontrols effects Creasing excitation while increasing efficient energy productIOn.

several effi·ect.·ve _l:" . . -_.......... t"" "'""'..,,...........o death from shock can give us insight into this gen-eral process of the failure of life, and so into the nature oflife itself.

The average biology professor is just about as unsophisticated as the average television-viewer about water in organisms--how it got there, why it stays there, what it does. The typical biologist maintains the conventional view of the cell by changing the subject whenever a fact conflicts ith a doctrine. The history of the "cell membrane" shows how this mental process has worked.

At first,Q was thought to account for the different composition of the tions around cells, and inside cells. Then mem-brane pumps" were introduced to explain e differences, because too many facts were inc sis-tent with the simple membrane idea. rote" s were found and .identified as the pump . en it turned out that pumps would req " e energy that .cells .couldn't (aI!d. needn't) .provide, and many ways were devised to explain: the mirn.inaIenergy needed to maintain the composition of cell water. But the "pump-proteins"--calcium-ATP-ase, sodium/potassium ATPase, etc.-are proteins that really exist, though their functions are much more interesting than "pumping." An important context for thinking about these ATPases is that the con-tractile protein of muscle (myosin) is a calcium-dependent ATPase.

The habit of biochemists has been to think of enzymes as the soluble proteins that could be ex-tracted from cells in a watery solution, and to ig- nore the insoluble residue, which contained the ATPases. Now, much of the residue has' been res-urrected for biochemistry, under the name of "membrane proteins. II The "ghost" of the red blood cell, after it has been shocked into losing its -hemoglobin, is a popular lab preparation that bio-chemists like to call a "membrane," though the term is grossly misleading. Szent-Gyorgyi, Gilbert Ling, and a few physically conscious biologists spoke of these relatively insoluble proteins' as structural proteins.

In 1968 or '69, I had been reading the previous' 50 years of research on cell physiology, and I saw th<>t £':::- 18 years, Gilbert Ling had been almost alone in offering a view of the cell that was physi-cally possible. He had solved the problems of .ionic regulation in ways that physical chemists could accept, but biologists were proceeding as if his solutions to their problems didn't exist. I wrote· to him, to see if I, as a newcomer to "science," was missing something. He said that I just didn't understand what "science" was; it was a matter of money, prestige, and influence, with little concern for what was true.

It has been calculated that the substances which are distributed unequally between cells and "j the surrounding fluid would require 15 times as Surprisingly, stimulated nerves have been observed much energy as the cells can produce, if their dis-to absorb heat immediately after releasing it; iIi a tribution had to be maintained by pumps, but it has "refiigerator-like" process that coincides with their also been demonstrated that cells can remain al-electri,cal repolarization. No one was able to ex-most at equilibrium, when their energy production plain this on the basis of membranes and pumps, is completely blocked by poisons. Something since the pumps should be releasing their heat af- . maintains the ions and other solutes in their ter stimulation and during repolarization. unequal distribution between the inside and I have thought of this in terms of Kelvin's idea outside of the cell, but it doesn't take energy to ofincreased surface area leading to decreased tem-do This is why cells have been compared to. _ perature.. What we. ion-exchange resins, which also have the ability the way energy can be used in ree'stablishing the to passively select certain ions while excluding cell's resting condition. without releasing heat, others. People who have examined theatom-by-might be the idea that physical processes (the atom physics of how an ion-pump illight work change of protein conformation and water struc-have demonstrated the silliness of the idea. Ion-ture) are intimately integrated with chemical exchange granules selectively bind certain ions that equilibria. reach them by passive diffusion, and similar near-Around 1970, a famous English researcher was in Eugene lecturing about his' theory that the fa-mous "high energy bond of ATP" (14 kcal, I think he said) could be used to explain muscle contrac-tion. I had just read an old paper by one of my professors, Sidney which showed that its bond energy wasn't nearly so high. When I asked Bernhard why "everyone talks about ATP's high-energy bond," he just said "everyone doesn't."

equilibrium processes can account for the ion gra-dients maintained by cells. The interesting differ-ence in cells (compared to ion-exchange resins) is that their physical near-equilibrium is closely bal-anced with chemical processes, which are also much closer to equilibrium than conventional schemes imagine.

the silliness of the "pump". idea demystifies the membrane idea, and then a person can begin to think about how cells really work.

,..-r Stimulated, active cells expend energy. Be-! sides doing measurable work, such as contraction, , they release a measurable amount of heat, at the moment of responding to stimulation.

When ATP breaks down it absorbs water, and when it is synthesized, water is released. In a water-free environnient, the equilibrium favors the formation of ATP. The chemical activity of water in cells is lower than it is in ordimL'-y water. Given the right (anhydrous) environment, ATP will form spontaneously. As the reactants form ATP and give up water, energy is (at least theoretically) ab-sorbed by the chemical bond. In the abstract, this shows that the formation of ATP and the absorp-tion ofenergy could be caused by factors that con-trol the activity or availability of water. The protein-ATP complex is one of those water-regulating factors.

The abstract idea that ATP could be formed by a '-"relaxlng" cell (re'covering from stimulation) goes against the idea that a "cell .. is a motor and ATP is the fuel." Some people have argued that the contraction occurs first, caus-ing ATP to be split, rather than the reverse. Other examples of enzyme activation support this view, that the contraction or activation is a physical process, like releasing a spring. In the contracted· § r state, sodium is able to enter the cell momentarily, and the presence of sodium seems to allow the ATP to be reformed. These differences might seem subtle, but they have made an all-or-none difference in the minds of medical peo-ple deciding on therapies and diets.

This picture of a cell as a loaded spring, or as analogous to the ion exchanger in a water-softener, is the sort ofimage I have' in mind when I speak of"charging the . : Several researchers have demonstrated that in--=travenous injections of ATP prevent death from shock, that shock depletes the ATP of the cells, ..and that depleted cells absorb ATP much more readily than normal cells that don't lack it. All of the biologists and biochemists (at Oregon's Insti-tute for Molecular Biology) that I mentioned this to said it was impossible, "because ATP is highly ionized and can't cross the cell membrane."

Even when a general idea is clear and consis-tent with the facts, ifit opposes the dominant view it needs some experiments that can hardly be un-derstood without it. \' Liver ATP is increased as a result of in- Lcreasing blood sodium. An increase of only about 15% in the blood sodium, for example, caused the cells' ATP to nearly double. [R. L. Veech, et al., "Relationship offree cytoplasmic py-rophosphate to liver glucose content and total py-rophosphate to cytoplasmic phosphorylation potential," FEBS Lett. 117, K65-72, 1980.] Sodium is an "extracellular" ion, one that binds water to itseif so strongly that it is excluded from the cell under normai co.nditions, in which the wa-4.-ter is dominated by the cell's structural molecules.

It is only when the cell is stimulated or fatigued -that it absorbs larger amounts of sodium, and the -fatigued cell also absorbs an excess of water. The textbooks say "water follows sodium," but the physical reality is that sodium also follows (free) water, and that it tends to be excluded from the water of cells. Increasing the sodium in the en-vironment of a water-logged cell will tend to dehydrate the cell.

experiment, using sodium to increase ATP (especially when we remember that ATP is an effective treatment for shock) shows how [ hypertonic sodium might rescue a shock victim, in-creasing circulatory efficiency, helping to increase bloogvolume, restoring the cell's electrical and chemical resting state, and possibly regulating in-tracellular pH. [G.. B. Haycock, "The influence of sodium on growth in infancy," Pediatr. Nephrol. 7(6), 871-875, 1993.] The increasing blood vol-ume is a "mechanical" effect that helps to make the use of hypertonic sodium culturally more accept-.able, but it is really secondary to the other effects .

of sodium. The first water to be restored to the serum is that contained in red blood cells and the swollen endothelium. Capillaries and small blood vessels that have been obstmcted by swollen en-dotheiial cells aliow free passage of the blood, and the increased water lowers the blood's viscos-ity, improving its ability to deliver oxygen and glucose. Brain swelling is reduced, and conscious-ness is restored. Glucose metabolism is also im-proved under these conditions. . Sodium causes the ATPase to produce ATP, rather than consuming it. (p.I. Garrahan and 1. M. Glynn, "The incorporation of inorganic phos-phate into adenosine triphosphate by reversal of the sodium pump," I. Physiol. 192, 237-256, 1967.; P. A. Dibrov, et al., "A study on Na+-coupled oxidative phosphorylation: ATP fO,rma-tion supported by artificially imposed delta pNa and delta' pK in Vibrio alginolyticus cells," 1. Bio-energ. Biomembr. 21(3),347-357, 1989.)

The membrane-pump theory says that the cell consumes ATP to expel the sodium which enters, and increased external sodium increases its likeli-hood of entering the cell, but in realiry increased external sodium causes more ATP to be produced. The precise balance of ions seems to make the difference between consumption or production ofATP. [t. Plesner, et al., "[32P]ATP synthesis in steady state from [32P]Pi and ADP by Na+/K+-ATPase from ox brain and pig kidney. Activation by K+," Biochim. Biophys. Acta 1040(2), 167-174, 1990.] Remembering that the muscle protein is an ATPase, there is a situation that I think is analo-gous. When a muscle is stretched, it forms ATP, . rather than consuming it. This could be the res4lt ofa slight change in the physical state ofthe water and small changes in chemical affinities produced '\ t by the changes in protein conformation. Before this effect of stretch on ATP synthesis was directly observed, Starling's law of the heart recognized j the force ofcontraction increased with the ini- 1 tial length of the muscle fiber. Simply increasing lood volume increases the effectiveness of the eart contraction. Szent-Gyorgyi described a re-'lated process (the "staircase" phenomenon) as "function building structure, structure producing function. " . .

--' Sodium is required for cells to absorb glucose -and amino acids. I have recommended salty foods I --at bedtime to promote sleep, because of sodium's _ recognized anti-adrenalin effect. There are some complicated ways of thinking about its effect on adrenalin, as there are for explaining its ther-mogenic effect, but the simple fact that it is needed for absorbing glucose can explain its ability to lower adrenalin (since adrenalin rises when glu-cose is needed) and to increase heat production.

In the fetus and the newborn baby, sodium promotes growth.. Progesterone, sodium and glu-cose are often limiting factors in the growth of the baby's b'rain; they are deficient, cells die in-stead ofgrowing.

fact is that sodium energizes. It helps to remove calcium from the cell, (0 produce ATP, and to promote absorption ofglucose and amino acids. The fear many physicians have of injecting hypertonic sodium chloride is odd, in the light of the knowledge that has accumulated in recent dec-ades. Chloride isn't always the ideal anion, but more elaborate preparation is needed for providing the ideal ionic solution.

Carbon dioxide is powerfully involved in the regulation of both sodium and calcium, as well as in respiration and energy production. . It tends to relax both nerves and muscles. It is apparently one of the essential factors in prevent-ing edema. [For example, in the cornea; M. V. Riley, et al., 1995.] ATP and C02 both bind to hemoglobin, regu-lating its affinity for oxygen. The way in which they bii:Id to this protein indicates that they Will bind to many other intracellular proteins, similarly regulating the functions ofthose proteins. . . .

The elimination ofwater from the envirOliment in which ATP is formed or decomposed favors its formation, and in this environment ATP doesn't contain its reputed "high energy bonds," but it still has its strong affinity for binding to proteins. So-dium binds water to itself, and it is this feature that leads to its exclusion from the normal cell. C02, when it is in water, especially with the carbonic anhydrase enzymes, combines with water. As it is formed in the mitochondria, this means that it will carry water (as well as calcium and sodium) out into the cytoplasm, and out of the cell.

In many situations, including brain hypoxia, carbon dioxide is the decisive protectivefactor.

Low thyroid function involves reduced forma-tion of carbon dioxide, and the body fluids don't retain as much sodium as in normal individuals. Both urine and sweat tend to contain abnormally high sodium concentration in hypothyroidism. Be-cause C02 is central to the regulation of pH, and hydrogen ion excretion (acid urine) is orie mecha-nism involved in sodium retention, the C02 defi-ciency of hypothyroidism is probably closely connected with the inability to retain adequate sodium.

The body fluids are actually hypotonic in hypothyroidism.

If hypertonic sodium energizes, then the low-sodium hypoosmotic fluids of hypothyroidism de-energize.

Low-thyroid cells are also unable to retain magnesium efficiently, and a magnesium deficiency prevents muscle relaxation, wasting energy. Ade-quate sodium prevents urinary magnesium loss.

Hypothyroidism tends to cause hypoglycemia, and the lack of glucose (even if it is because the glucose in the blood can't be absorbed because of insufficient sodium) causes elevation of adrenalin. Hypertonic sodium given intravenously lowers the amount of adrenalin in the blood, just as' the thy-roid hormone does.

Hypothyroidism also causes an imbalance be-tween the antiestrogenic antishock hormones, pro-gesterone and pregnenolone, and proshock estrogen.

The close integration of physical and chemical processes when those processes are near equilibrium is the fact or the principle that is lack-ing in the doctrine the cell is like a collection of motors, fueled by ATP. If you can imagine a Chevrolet that at times creates gasoline while ab-sorbing heat, then the simile would be acceptable. The inappropriateness ofthe mental image ofa cell with pumps and motors leads to the treatment of shock with things that produce shock, ofheart fail-ure with things that produce heart failure, and of aging with things that accelerate aging.

NOTE: *The estrogen dominance which is needed to start the reproductive cycle, with cell prolif-eration in the endometrium, breast, and pituitary, is not otherwise useful to the organism, and is controlled and opposed during pregnancy by a constantly rising pro-duction of progesterone. The state of estrogen domi-nance is essentially unstable. P. T. Ellison, emphasizing the "energy hungry brains" of primates, explains the need for the massive endometrial groWth in primates, and Strassman observes that endometrial re-gression occurs in all rnanunals. These are important points. Their failure to point out that estrogen has many undesirable systemic effects very likely results from the cultural context that has been created by the estrogen-promoting pharmaceutical industry.

The group of processes that we call the immune system is so deeply integrated with evefYthing else in the organism that to talk about the reason for evolving it" is as misleading as to talk about the reason" for evolving certain pigmentations-black feathers, for ex-ample, are mechanically stronger than white ones, se-lection of foxes for domesticability changes their fur pigmentation and their voice, selection for egg laying somehow suppression of feather pigmenta-tion, etc., yet people like to talk about protective col-oration, because an easy conn.ection can be made between that and genetic selection. Being an organism is a problem whose solution may require inventive use of internal and external resources; chromosomes are in-ternal resources, not clusters oftraits.

The ideology that sees the organism as a sum of traits, each with its gene, has been a failure in provid-ing understanding about how an organism comes to exist.

.

I. H. Chaudry, et aI., "Evidence for enhanced up-take of ATP by liver and kidney in hemorrhagic shock,"

Am. 1. Physiol.: Regulatory Integrative Compo Physiol. '2(2), R83-R88, 1977. (During shock there is progres-sive dephosphorylation of ATP, ADP, AMP, and cre-atine ' phosphate. "...the beneficial effect of ATP-MgCI2 -in shock could be due to provision of en-ergy directly to tissue in which ATP levels were lowered.")

G. P. Sharma and B. Eiseman, "Protective effects of ATP in experimental hemorrhagic shock," Surgery 59,66-74, 1996.

S. M. Talaat, et aI., "Effects of adenosine triphos-phate administration in irreversible hemorrhagic shock," Surgery 55,813-819, 1964.

G. R. Bartlett, The Human Red Cell in Vitro, pages 5-29, Greenwah and Jamieson, eds., Grune and Stratton, London, 1974. (After cold storage, red cells lose much of their ATP and are likely to die soon after transfusion. They can be incubated in nucleosides to increase their ATP and improve their survival.)

P. M. Grinwald., "Positive feedback in the living process: The role of ATP in ischaemic cell death," Med. Hypotheses 3(1), 138-143, 1977. (Depletion of ATP leads to increased entry of calcium into cells which uncouples phosphorylation, and further lowers ATP.)

M. Koike, et aI., "Gluconeogenesis stinlulated by extracellular ATP is.triggered by initial increase in the intracellular Ca2+ concentration ofthe periphery of hepatocytes," Biochem. 1. 283(Pt 1), 265-272, 1992. ("Extracellular ATP stimulated glucose synthesis." "The rate of the initial fast component did not depend on the presence or absence ofextracellular Ca2+....")

K. D. Keef, et aI., "Purinergic relaxation and hy-perpolarization in guinea pig and rabbit coronary ar-tery: Role of the endothelium," 1. Pharmacol. Exp. Ther. 260(4),5.97-600, 1992.

A. S. Piper and M. Hollingsworth, "ATP and beta,gamrna-methylene ATP produce relaxation of 'guinea-pig isolated trachealis muscle via actions at PI purinoceptors," Eur. 1. Pharmacol. 307(2),183-189, 1996.

B. Boland., et aI., "ATP induced-relaxation in the mouse bladder smooth muscle," Br. 1. Pharmacol.

108(3), 749-753, 1993.

Y. Sakai-Tomita, et aI., Na(+)-eoupled ATP syn-thesis in a mutant of Vibrio parahaemolyticus lacking H(+)-translocation ATPase activity," Biochem. Bio-phys. Res. Comrnun. 179(1),224-228, 1991.

V. P. Skulachev, "Membrane-linked energy trans-ductions. Bioenergetic functions of sodium: H+ is not unique as a coupling ion," Eur. 1. Biochem. 151(2), 199-208, 1985.

I. T. Velasco, et aI., "Hyperosmotic NaCI and se-vere hemorrhagic shock,": Am. J. Physiol. 239(5), H664-673, 1980. ("...hyperosmotic NaCl infusions in-crease the dynamic efficiency ofthe circulatory system, enabling it to adequately handle oxygen supply and me-tabolite clearance, despite a critical reduction of blood volume.")

M. Rocha e Silva, et aI., "Hyperosmotic sodium salts reverse severe hemorrhagic shock: Other solutes do not," Am. 1. Physiol. 253(4 Pt 2), 1987. G. Ronning, et ai, "Intraosseous infusion of a small volume of hyperosmotic fluid increases mean arterial pressure and lessens the catecholamine response in pigs '>'\<'ith haemorrbagic shock," Eur. J. Surg. 161(10), 715-720, 1995.

G. Ronning, et aI., "Effect of haemorrhagic shock and intraosseous resuscitation on plasma and urine catecholamine concentrations and urinary clearance in pigs," Eur. 1. Surg. 161(6), 387-394, 1995. ("Two hours after the whole blood infusion the catecholamine concentrations of the treated animals were at baseline values, significantly lower than those ofthe controls.")

. G. Ronning, et aI., "Influence of intra-osseous infu-' sion of a small volume of hyperosmotic fluid on beta- . adrenergic function in circulating lymphocytes from bled pigs,"·Scand. J. Clin. Lab. Invest. 55(6), 505-511, 1995. (Hyperosmotic treatment attenuated the plasma catecholamine release.)

. P. F. Moon, "Fluid conipartrnents in hemorrhaged rats after hyperosmotic crystalloid and hyperoncotic colloid resuscitation," Am 1. Physiol. 270(1 Pt 2), FI-8, 1996. . E.H. Luh, et aI., "The effects ofhyperosmolarity on the viability and function of endothelial cells," 1. Surg. Res. 60(1), '122=128, 1'996: ("...exposure to anoxia inay induce tolerance of endothelial cells to hyperos-motic media.")

M. C. Mazzoni, et aI., "Capillary narrowing in hemorrhagic shock is rectified by hyperosmotic saline-dextran reinfusion," Circ. Shock 31(4), 4-7-418,1990.

J. M. Pascual, et aI., "Resuscitation of intraopera-tive hypovolemia: A comparison of normal saline and hyperosmotic/hyperoncotic solutions in swine," Crit. Care. Med. 20(2), 200-210, 1992.

M. C. Mazzoni, et aI., "Dynamic fluid redistribu-tion in hyperosmotic resuscitation of hypovolemic hem-orrhage," Am. J. Physiol. 255(3 Pt 2), H629-637, 1988. ("...immediately after hyperosmotic infusion, wa-ter shifts into the plasma first from red blood cells and endothelium and then from the interstitium and ·tissue cells."

. K. and U. Kreimeier, "Microcirculatory therapy in shock," Resusci!ation 18(Suppl.), S51-61, 1989. ("...restoration of vasomotion and reopening of narrowed capillaries can be obtained by small volume resuscitation using hyperosmotic/hyperoncotic salt dex-tran solution.")

F. Christ, et aI., "Hyperosmotic-hyperoncotic solu-tions during abdominal aortic aneurysm resection,"

Acta Anaesthesiol. Scand. 41(1 Pt 1), 62-70, 1997. (We suggest that HHS opens new perspectives in pe-rioperative fluid management of both elective and emer-gency AAA repair, since hemodynamic parameters are improved and the overall fluid balance is less positive, thus decra.1sing the li.1<elihood ofedema formation.")

1. de Felippe, Jr., et aI., Treatment of refractory hypovolaemic shock by 7.5% sodium cWoride injec-tions," Lancet 2(8202), 1002-1004, 1980. ("The im-mediate effects of the NaCI injections were a moderate rise in arterial pressure, the resumption of urine flow, and recovery ofconsciousness."

C. Veigel, et aI., "The influence of ionic strength upon relaxation from rigor induced by flash photolysis of caged-ATP in skinned murine skeletal muscle fi-bres," Pflugers Arch. 430(6), 994-1003, 1995.

M. V. Riley, et aI., "The roles of bicarbonate and C02 in transendothelial fluid movement and control of corneal thickness," Invest. Ophthalmo1. Vis. Sci. 36(1), 103-112, 1995.

E. C. Wirrell, et aI., Will a critical level of hyperventilation-induced hypocapnia always induce an absence seizure?" Epilepsia 37(5), 459-462, 1996. ("...a reduction in number of spike and wave bursts' and tOtal seconds of spike and wave was noted in children breathing supplemental C02....Supplemental 02 had no effect.")

V. D. Solomatina, "Peculiarities of phosphoric compound metabolism in liver mitochondria of carp adapted to higher concentration of C02 in water," Ukr. Biokhim. Zh. 52(2), 183-186, 1980. ("...during adap-tation to the C02 higher level in the medium the . amount ofATP in fishes Undergoes the most significant changes." "When fishes were for 24 hours under condi-tions of the O.4mM C02 concentration, the ATP con-tent in the carp liver mitochondria surpasses the control leveL..")

S. F. Badylak and C. F. Babbs, "The effect of car-bon dioxide, lidoflazine and deferoxarnine upon long term survival following cardiorespiratory arrest in rats," Resuscitation 13(3),165-173,1986.