LIFE SCIENCES Dol . 20, pp,597-608, 1977 . Printed in the U .S .A .

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GLUCOSE METABOLISM IN THE HYPOTHERMIC PERFUSSD RAT HEART S . Rirby Orme, M .D . * and Gregory A . Belly, B . A . Department of Surgery, Duke University Medical Center Durham, North Carolina 27710 Blaue Brendel, Ph .D . and Rubia Bresaler, M .D . Department of Pharmacology, University of Arizona Medical Center Tucson, Arizona 85724 (Received in final form December 13, 1976) SUMMARY Although hypothermic whole organ perfusion is widely used is atteapts to preserve organs for transplantation and to preserve the myocardi~ during cardiac surgery, little ie known about substrate metabolism during hypothermia . A knowledge of metabolite utilization during hypothermic whole organ perfusion might allow optimal substrate choice for preservation of energy stores and functional capacity . Separate groups of hearts from fed rate were perfused 30 minutes with Rreba Henseleit bicarbonate buffer containing 5mM glucose-U- 14 C, at . 37 ° , 25 ° , 20 ° , 15 ° and 10 ° C . From 37 ° to 15 ° C, heart rate decreased 90x and coronary flow decreased 25x . Glucose uptake decreased 5 fold from 37° to 10 ° C while 14COp and lactate production decreased 50 fold and 28 fold, respectively . Myocardial glycogen was stable until 10 ° C at which point increased glycogenolysis occurred . The incorporation of 14C in glycogen was stable at 37 ° , 30 ° and 25 ° but decreased progressively with lower temperatures . The percent recovery of glucose ae 14C02, lactate and 14C in glycogen decreased from 73x at 37 ° to 3 .4x at 10 ° C . Our studies indicate that metabolism of glucose is greatly reduced but significant above 15 ° C . The ability to preserve organs for weeks to months in vitro would have immediate important applications . It would allow greater salvage of cadaver organs, time for careful tissue typing and preparation of the recipient for eventual transplantation, and assessment and perhaps improvement of the functional capacity of the donor organ prior to transplantation . To prevent cellular death or injury in the excised organ, metabolism must be slowed by hypothermia or metabolic inhibitors (1,2) . Alternatively, the organ may be perfused to supply oxygen and nutrients and remove carbon dioxide . Although freezing successfully preserves erythrocytes (3) and spermatozoa (4) up to 4 years, freezing of whole organs results in serious damage incompatible with recovery . The moat successful organ preservation to date combines perfusion with hypothermia . With this technique, it has been possible to store canine *Supported by Grant GM-1709, HE-07061,AM-12706 of the USPHS . Current address : 125 East Idaho St ., Boise, Idaho 83702 . 597

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kidneys as long as 4-5 days with subsequent function upon transplantation (5) . Attempts to extend this period have centered upon making the perfusion as physiological as possible with attention to perfusion pressure, type of flow (puleatile or non-pulsatile), venous outflow pressure, perfusate composition, method of oxygenation, bacterial growth, tissue edema and capillary occlusion (6) . If a hypothermic perfused organ were to remain viable for weeks to months, it would have to extract nutrients and maintain energy stores in order to perform the work of active transport, molecular synthesis, and in the case of the heart mechanical contraction . Surprisingly, little is known about substrate metabolism of intact organs during hypothermia . A knowledge of metabolite utilization during hypothermic whole organ perfusion might allow optimal substrate choice for preservation of energy stores and functional capacity . Such knowledge would also be of benefit as an aid in agocardial preservation during cardiac surgery . The moat popular current methods of myocardial protection during open heart surgery are continuous coronary perfusion (7) and topical myocardial hypothermia without coronary perfusion (8) . In the report to follow, the metabolism of glucose by the isolated rat heart perfused over a temperature range of 10 ° - 37 ° C ie described . The data show that glucose uptake, COp production from glucose, set lactate production and incorporation of glucose into glycogen decrease markedly with hypothermia . These findings are discussed in terms of the known effects of temperature on biological processes and the effect of hypothermia on glucose metabolism in the intact animal . Material and Methode Heart Perfusion - The method of perfusion and design for the modified Langendorff apparatus were provided us by Drs . H . E . Morgan and J . R . Neely (9,10) . Male Sprague-Dawley rata, weighing 250-300 grams and having free access to food and water, were given 2 .5 mg of heparin intraperitoneally 30 minutes prior to use . The animals were decapitated and the heart was immediately excised and placed in 0 .9x saline at 4 ° C . The aorta was ran nulated and retrograde coronary perfusion was begun from a gravity reservoir placed 70 cm above the heart . The perfusate was a non-recirculating Rrebs Henseleit bicarbonate buffer (11) containing Ca EDTA (0 .5 mM), heparin (1 unit/cc), and continually gassed with 02 :COp (95 :5) . It was discarded into a drain tray as it dripped from the pulmonary artery and right atrium . The temperature of the perfusate leaving the heart was 37 ° C . After 12 minutes, if the heart demonstrated a satisfactory rate and coronary flow, it was placed in the perfusion apparatus and recirculating perfusion at 60 mm Hg pressure was begin . Temperature was varied by circulating cold or warm water through the water jacketed perfusion apparatus .* A thermometer was placed such that effluent from the heart dripped directly on the bulb . Perfusions were performed on different groups of hearts at 37 ° , 30 ° , 25 ° , 20 ° , 15 ° , and 10 ° C . Temperature variation between hearts in a series was not greater than 0 .5 ° C . For each group of hearts perfused at a lower temperature, control hearts at 37 ° were simultaneously perfused . Perfusions were carefully timed so that all steps were performed at equal time intervals . Because the solubility of gases increases with decreasing temperature, it was necessary to increase the sodium bicarbonate and decrease the sodium chloride (by equimolar amounts) at temperatures of 20 ° C and below in order to maintain the pH of the perfusate is the desired range . The buffer was as described above except that heparin was omitted and 5 mM Dglucose plus tracer amounts of D-glucose-U- 14C were added . The recirculating *4-8605 Wide Range Lab Bath - Americas Instrument Co ., Silver Springe, Maryland .

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buffer was continuously gassed with 02 :002 (95 :5) . After the heart had equilibrated in the apparatus for 6 minutes, an initial sample of perfusate was removed for determination of glucose and. lactate. The remaining perfusate volume was 20 cc . The effluent gas from the airtight perfusion system was now passed through a 002 trap and a time perfusion of 30 minutes was begun. During this period heart rate and coronary flow were recorded . At the end of the period a second perfusate sample for glucose sad lactate was obtained . The heart was frozen, while still being perfused, between aluminum blocks cooled in liquid nitrogen (12) . Measurement of Heart Rate and Coronary Flow - Heart rate was determined visually and coronary flow measured by counting drops leaving the heart . pH and Oa9gen Tension - pH was measured oa samples taken up is glees capillary tubes as the perfusate dripped from the hearts . Determinations were performed with a capillary pH electrode (Radiometer Copenhagen) . Oaygea ten eions were measured oa perfueates from separate groups of hearts perfused at identical temperatures . The method of sampling was that described by Nealy, et al . (13) . An oxygen electrode (Radiometer Copenhagen) was used . 14002 Collection and Analysis - Effluent gas from the airtight perfusion system was bubbled into a glass counting vial containing 10 .5 ml of 002 trapping agent (ethylene glycol monomethylether : 2 amiaoethanol, 9 .5 :1 v/v) . Ten ml of scintillator solution (7 .2g 2,5-dipherylozazole/1 ., 0.18 g 1,4-bis-(bie(4-methyl-5-phe~loaazolyl-2-)-benzene/1. in toluene, was added to each vial (14) . Residual 4002 in the perfueate was determined by placing 3 ml of parfusate is Erlenmeyer flasks fitted with polypropylene center wells . The flasks were quickly closed with serum stoppers . 4N H2 S04 (0 .2 ml) was added to the perfusate with a needle and syringe . Hydrozide of hyamine (0 .2 ml) was added to the center well and the flasks were agitated in a Dubnoff shaker for 60 minutes at 0°C. At the sad of this period, the center well was removed and placed in a scintillation vial containing 15 ml of a solution of 4 g 2,5dipheayloaazole and 0 .1 g 1,4-bis-(2,5-pheaylozaaolyl)-benzene/1 . in toluene . Recoveries of 14002 from NaH14C0 , circulated in a mock perfusion, by these procedures ranged from 93-97X . ~or determination of radioactivity in the initial perfusate, 0 .5 ml was added to a vial containing 2 ml of water plus 18 ml of scintillator solution (4g 2,5-dipheayloaazole and 0 .4 g 1,4-big-(2,5pheaylozazolyl)-benzene/0 .61. of toluene plus 0 .31 . of Triton R-100 . All samples were counted in a Packard Tri-carb scintillation spectrometer and corrected for quenching by the channels ratio method (15) . Analysis of Perfusate and Tissue Samples - Glucose uptake and lactate production were estimated by measuring changes in the perfueate concentration (16,17) during a 30rminute period of recirculation . The fronen hearts were ground to a powder with a mortar sad pestle cooled to the temperature of liquid nitrogen . Weighed aliquots of the powder were used for estimation of dry weight (10) and glycogen content. The final glycogen solution was divided, one portion Was combined with aathrone reagent to determine residual glycogen (18) while the other portion wan added to a counting vial containing 1 m1 of water sad 18 ml of the toiuéne - Triton R-100 scintillator solution to determine incorporation of 14 0 into glycogen. Caüüting was carried out ae described above. Materials - D-glucose-U- 14 0 was obtained from New England Nuclear Corporation, Boston, Massachusetts . Temperature Effects - The effect of temperature on a given process is expressed as the Q1p and as the Arrhenius temperature coefficient,u (19) . The

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410 ~ the ratio of reaction rate at a given temperature to the rate of the same reaction at a temperature 10 ° C lower . The Arrhenius coefficient u, is determined according to the equation v ~ Aé ~Ri in which v m velocity, R gas constant, T ~ absolute temperature, A ~ constant of integration, and the temperature coefficient . When the log velocity of a reaction is plotted as a function of 1/T, conformity to the equation is indicated by a straight line with a slope proportional to u . Expression of Results - The dry/wet ratio of the frozen heart powder was used to eapresa all values per gram of dry weight . Results Heart Rate and Coronary Flow - Heart rate and coronary flow, in separate groups of hearts perfuaed at various temperatures, are shown in Figure 1 . Each heart underwent a 12 minute washout perfusion at 37 ° C prior to a recirculating perfusion at the indicated temperature . The maximal rate and coronary flow changes had occurred by the end of the 6 minute equilibration period, at which time the 30 minute teat perfusion was begun. Heart rate and coronary flow were stable over this 30 minute period . Heart rate fell steadily from a mean of 238 at 37 ° to 25 at 15 ° C . At 10 ° C, the mean rate was only 0 .17 beats/min . Coronary flow decreased moderately from 55 .5cc/min/g dry wt . a t 37 ° to 42 at 15 ° C . There was a further decline to 29 at 10 °C . Over the interval from 37 ° to 15 ° C heart rate decreased 90Z while coronary flow decreased 25x . These decreases in heart rate and flow are consistent with the findings of others (20) . pH and Oxygen Tension - The pH of the perfusate was determined at the end of the perfusion for each heart . The mean pH was 7 .39, 7 .39, 7 .35, 7 .33, 7 .39, and 7 .37 for the hearts perfuaed at 37° , 30 ° , 25 ° , 20 ° , 15 ° , and 10 ° C . From studies of Delcher and Shipp (14), we can conclude the range of pH in these eaperimenta is not great enough to alter glucose metabolism by the perfuaed heart . The oxygen tension of perfusate entering and leaving the heart was obtained on separate groups of hearts (3 determinations on each of 2 hearts/ group) perfuaed in an identical manner and at the same temperatures as the other hearts in this study . Oxygen tension of perfusate entering the heart was 455 mm Hg at 37 ° and increased to 720 mm Hg at 10 ° C . The mean effluent oxygen tension was lowest at 37 ° C (210 mm Hg) and increased to 690 mm Hg at 10 ° C (all tension readings were made at 37 ° C) . The oxygen tensions obtained at 37 ° C are comparable to those found in similar systems (9,21) and are believed to indicate adequate oxygenation . Glucose Metabolism - The effect of temperature on glucose uptake, 14 COZ production, net lactate production, residual myocardial glycogen content and incorporation of 14C (from I~glucose-U- 14 C) into glycogen ie shown in Tables 1 and 2 . Glucose uptake decreased from a mean of 129 M/g dry wt ./30 min at 37 ° to a mean of 25 pM at 10 ° C . 14 C02 production decreased from a mean o£ 50 uM glucose eqûivalents/g dry wt ./30 min to 1 ~ at 10 ° C . There was a sharp decline in C02 production between 15 ° ând 10 ° C . Net lactate production decreased from 22 .4 uM glucose equivalents/g dry wt ./30 min to .8 uM (mean values) . In contrast to the uniform decrease in glucose uptake and 14COp production with temperature, net lactate production wen similar at 25 ° , 20 ° and 15 ° C . The overall decrease, however, ie apparent . Residual glycogen was stable until 10 ° C at which point increased glycogen breakdown occurred . The incorporation of 14 C into glycogen was stable at 37 ° , 30 ° and 25 ° C . 14 C into glycogen was decreased uniformly from this point reaching a low value of

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FIG. 1 Heart fate and coronary flout (mesa + S.E . of mesa) of Langeadorff perfueed Fat hearts in relation to temperature . Hearts from rata with coatiauoue access to food vere perfused in a recirculating syetea for 30 minutes vith Rrebs.Heaseleit bicarbonate buffer containing 5~i D-glucose . Separate groups of hearts vere perfused at each temperature as described in Experimental Procedure .

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1 .8 uM/g dry wt ./30 min at 10 ° C . The percent of glucose uptake (30-40X) accounted for by 14 C02 production is essentially constant from 37 ° to 15 ° C, whereâe, at 10 ° C only 4X of the glucose uptake is accounted for by 14C02 production . The percent of glucose uptake accounted for by lactate production decreases as the temperature is lowered . Again the values from 25 ° to 15 ° are similar . The incorporation of 14C into glycogen is variable with a definite decrease at 10 ° C . The per= cent recovery of carbohydrate (see footnote-Table 2) decreases from 73X at 37 ° to 3 .4X at 10 ° C . Glucose uptake, 14 C02 production, lactate production, residual glycogen and 14 C incorporation into glycogen are plotted as log velocities versus the reciprocal of absolute temperature in Figure 2 . The glucose uptake plot is a straight line conforming to the Arrhenius equation . The elope is proportional to the temperature coefficient,u , which is calculated to be 11,425 cal ./mole . The Qlp values for glucose uptake are 1 .7, 1 .8, and 2 .1 at 30 ° - 20 ° , 25 ° 15 ° , sad 20 ° - 10 ° C, respectively . The log versus temperature plots of 14 C02 and lactate production, residual glycogen and 14 C incorporation into glycogen are not straight lines and do not conform to the Arrhenius equation . All of these parameters, however, decrease with temperature . The 1 CO2 production slope is relatively constant over the temperature interval of 37 ° - 15 ° C . At 15 ° C a sharp break occurs as the velocity decreases very rapidly becoming almost nil at 10 ° C . The Qlp values for 14 C02 production are 1 .72, 1 .5, and 15 .9 for 30 ° - 20° , 25 ° - 15 ° , and 20 ° -10 ° C . The marked increase in Q between 20 ° and }0 ° C coincides with the sharp downward break in the log velocity versus~ T slope . There ie a break in the residual glycogen slope at 15 ° anA in the 1 ~C incorporation into glycogen elope at 25 ° C . Discussion The data presented here describes the effect of temperature upon the rate, coronary flow and glucose metabolism of the isolated perfused rat heart . From 37 ° to 15 ° C, heart rate decreased 90X and coronary flow decreased 25X . Glucose uptake decreased 5 fold from 37 ° to 10 ° C while 14 C0 2 and lactate production decreased 50 fold and 28 fold, respectively . Myocardial glycogen was stable until 10 ° C at which point increased glycogenolysis occurred . The incorporation of 14 C in glycogen was stable at 37 ° , 30 ° and 25 ° but decreased progressively with lower temperatures . The glucose from the increased glycogenolysis at 10 ° C (Table 1) does not appear as lactate and with the marked depression of 14 C02 production cannot be presumed to have been completely oxidized . It may appear as glycolytic intermediates between glycogen and lactate . As temperature drops the percent carbohydrate recovery diminishes (Table 2) . At normal temperatures up to 25Z of the uptake of 1 C-glucose has been found in glycolytic intermediates (23) . This percentage may increase with hypothermia and is addition free glucose may appear in the myocardial cell (24) or there may be increased incorporation of glucose into heart glyceridea . The decrease is glucose uptake, 14 C02 and lactate production with hypotharmia correlates quite well with the decline in heart rate . This may be a reflection of decreasing energy utilisation at slower heart rates . Our findings must be considered preliminary and leave many questions unanswered . It is evident that glucose uptake and utilisation is reduced as temperature decreases . Membrane transport of glucose is of major importance in controlling the rate of glucose uptake by the isolated perfuaed rat heart . Glucose uptake is known to be stimulated by the addition of insulin to the perfusion medium, by anoxia and by requiring the heart to perform work (9,25) .

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FIG. 2 Residual glycogen, glucose uptake, 14C in glycogen, 14 C02 and lactate production in separate groups of perfused rat hearts, ezpreeeed ae yM glucose/g. dry Freight/30 minutes (mean _+ S .E .), are plotted ae log rates versus 1/T . The calculated p value for glucose uptake is 11,425 cal./mole .

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These factors were purposely eliminated is this study in order to assess the effect of hypothermia as an independent variable . Similar studies combining hypothermia and insulin have not been performed by us but would be of great interest . The addition of insulin to the perfusion media might result in increased glucose uptake and subsequent utilization by the hypothermic perfused heart . Heart rate declined progressively with lower temperatures and this no doubt accounts for some of the observed decrease in metabolic activity . It might be possible to keep the heart rate constant, over some of the temperature range, with myocardial pacing . Thin would eliminate the added variable of declining heart rate uniformly noted during hypothermia . The functional capacity of the hypothermic perfused rat heart upon rewarming was not assessed . Certainly this is of great importance . Hearse and colleagues (26,27) have demonstrated that perfusion of isolated rat hearts at 4 ° C permits excellent recovery as evidenced bq the ability of the rewarmed hearts to perform external work with adequate heart rate, aortic and coronary flow . The ability of the hearts to recover correlated with the level of adenosine triphosphate (ATP) and creative phosphate is the myocardium at the end of the hypothermic perfusion . In contrast, they found that isolated rat hearts undergoing iachemic arrest (no coronary perfusion), maintained adequate levels of ATP and creative phosphate only when ischemia was combined with severe (4 ° C) topical hypothermia . Recovery rapidly deteriorated during ischemia with temperatures greater than 15-20 ° C . Our atudiea indicate that significant metabolism of glucose occurs at temperatures above 15 ° C . This stresses the need to be certain that myocardial temperature is low enough if topical hypothermia rather than coronary perfusion is chosen for myocardial protection during cardiac procedures . It would be of interest to repeat these eaperimenty utilizing fatty acids or keytones as substrates, to determine if the effect of hypothermia is comparable to that found for glucose utilization . Persistent hyperglycemia following glucose infusions has been noted is hypothermic animals (28,29) and man (30,32) . Fuhrman and Fuhrman could not demonstrate any glucose utilisation in rate cooled to 18 ° C . On the other hand, uptake o£ glucose by isolated rat diaphragm occurred at 18 ° C and Q p for the interval from 18 ° - 38° was 2 .55 (33) . Further, in vitro studies 34,35) have demonstrated that hexokinase activity and glycogen synthesis are present in rat muscle at temperatures less than 10 ° C . From observations in intact rata and hamsters, cooled to 14 ° C, Maur et al ., (29) concluded that the impairment in glucose utilization representeddecreased oxidative metabolism of carbohydrate ; there being no apparent decrease in the formation of lactic acid via pyruvic acid . Ia the hypothermic perfused rat heart (Table I) there are decreases in both 1 4C0 2 and lactate production . In the hypothermic intact animal sad man decreases in cardiac output and peripheral circulation occur (36) which can rresult in hypoxie, acidosis, and changes in the effective circulating pool of glucose . In addition, an inhibition o£ insulin release has been noted in infants undergoing deep hypothermia Por cardiovascular surgery (32) . These changea, .in turn, might account for the differences in glucose metabolism between in vivo models and the hypothermic perfused heart where coronary flow and perfusate oxygenation are adequately maintained . For biological systems, the parameters most frequentlq used to describe reaction rate changes with temperature are the Q l p and the Arrheaiua temperature coefficient (see Experimental Procedure) . Q1U values of about 2 are

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607

cowman for moat enzymatic reactions . Many physiological processes, consisting of multiple enzymatic reactions, have been found to follow the Arrhenius equation over certain biological temperature ranges . It has been suggested that, in a sequential series of catalyzed reactions which would be involved in a physiological process, the elwest of the aeries determises the p value for the overall rate (37) . Thus a change in u might be takes to indicate that a new step in the aeries has become rate limiting . Although such concepts are appealing, Stearn (38) has shown that the overall u value for a series of reactions nay agree with that of an individual catalyzed reaction only under limited conditions and that unless data is especially chosen any agreement between the overall u and a particular u for an elementary step is fortuitous . The Qlp values and the Arrhenius temperature coefficient (11,425 cal ./ mole) calculated for glucose uptake in the perfuaed rat heart are in the range obtained for biological processes. These values agree quite well with the findings of Fuhrman (34) for glucose uptake by the isolated rat diaphragm and differ from the marked temperature effect on glucose uptake seen in the intact hypothermic rat. Although the log rate versus 1/T plots of 14COp production, residual glycogen sad 14C incorporation into glycogen are not straight lines and do not conform to the Arrhenius equation, it is apparent that there are changes in their general slopes occurring within small temperature intervals (Figure 2) . The reaction rates decrease markedly ae particular temperatures are reached but these changes in elope do not necessarily indicate that a new step in the aeries of enzymatic processes making up the overall reaction hoe become rate limiting because of the objections raised by Steam (38) . References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10 . 11 . 12 . 13 . 14 . 15 . 16 . 17 . 18 . 19 .

W. R. WEBB, R. P . DODDS, M . 0 . üNAL, A. M. KAROW, W. A. COOK, aad C. R. DANIEL, A~ . Surg . 164, 343-351 (1966) . S . NAKAE, W. R . WEBB, K. E. SALVER, M. 0. UNAL, W . A. COOK, R. P . DODDS, and G . T. WILLIAMS, Ana . Thor . Surg : 3, 37-42 .(1967) . E . C . HIGGINS, Monogr . Surg . Sci. 3, 133-173 (1966) . J . K. SHERMAN, Cryobiology 1, 103-129 (1964) . A . L . HO?tPHRIES, JR ., Transplantation 5, 1138-1153 (1967) . J . C . NORMAN, Appleton-Ceatry-Crofts, New York (1968) . D . C . Mc000N, J. Thorac . and Cardiovasc . Surg . 70, 1025-1026 (1975) . R . B . GRIEPP, E. B . STINSON, aad N . E . SHIIMWAY,J. Thorac . and Cardiovaec . Surg . 66, 731-741 (1973) . H . E . 1~DRGAN, M. J . HENDERSON, D. M. REGEN, sad C . R. PARK, J. Biol . Chem . 236, 253-261 (1961) . H . E . MORGAN, J . R. NEELY, R. E . WOOD, C . LIEBECQ, H. LIEBERMEISTER, and C . R. PARR, Fed. Proc . 24, 1040-1045 (1965) . H. R. RREBS and R. HENSELEIT, 2. Phyeiol. Ch~. 210, 33-66 (1932) . A . WOLLENBERGER, 0 . RISTAN snd G . SHOFFA, Arch . Gea . Phyaiol. 270, 399412 (1960) . J . R . NERLY, H. LIEBERt{EI3TER, E . J . BATTERSBY, and H. E. MORGAN, Am . J. Phyeio1 :~212, 804-814 (1967) . H . K . DELCHEIt aad J. C. SHIPP, Biochem . Biophys. Act~ 121, 250-260 (1966) . R. J . HERBEBG, Packard Tech . Bltn : 15, 1-8 (1965) . A. StG . HQGGRTT and D . A. NELSON, Bioehen. J. 66, 12P (1967) . S. B. BARKER aad W. H. SITMMSRSON, J. Biol . Chem. 138, 535-554 (1941) . S. SEIFTER, S . DAYTON, B. NOVIC, aad E. MQNTWYLSR, Arch . Biochea. 25, 191-200 (1950) . R. H. TRIA~ORE, C . V. Mosby, Saint Louie (1966) .

608 20 . 21 . 22 . 23 . 24 . 25 . 26 . 27 . 28 . 29 . 30 . 31 . 32 . 33 . 34 . 35 . 36 . 37 . 38 .

Metabolism in Hypothermic Rat Heart

Vol . 20, No . 4, 1977

D . C . SABISTON, JR ., E . 0 . THEILEN, and D . E . GREGG, Surg . 38, 498-505 (1955) . L . H . OPIE, J . C . SHIPP, J . R . EVANS, and B . LEBOEUF, Am . J . Physiol . 203, 839-843 (1962) . .C J . SHIPP, Metabolism 13, 852-867 (1964) . L . H . OPIE, Am . Heart J . 77, 100-122 (1969) . C . R . PARR, J . BORNSTEIN, änd R . L . POST, Am . J . Physiol . _182, 12-16 (1955) . J . R . NEELY, H . LIEBERMEISTER, and H . E . MORGAN, Am . J . of Physiol . 212, 804-814 (1967) . D . J . HEARSE, D . A . STEWART and E . B . CHAIN, Circ . Res . 35, 448-457 (1974) . D . J . HEARSE, D . A . STEWART and M . V . BRAIMBRIDGE, Circ . Research 36, 481-489 (1975) . A . F . BICKFORD and R . F . MOTTRAM, Clin . Sci . 19, 345-359 (1960) . J . M . MAUR, D . M . McCOMISREY, J . W . HAYNES, and J . R . B&1TON, Can . J . Biochem . Physiol . _40, 1427-1438 (1962) . V . WYNN, Lancet _2, 575-578 (1954) . D . H . HENNF1~fAN, J . P . BUNKER, and W . R . BREWSTER, JR ., J . Appl . Physiol . _12, 164-168 (1956) . D . BAUM, D . H . DILLARD, and D . PORTE, JR ., N .E .J .M . _279, 1309-1314 (1968) . G . J . FUHRMAN and F . A . FUfUZMAN, Am . J . Physiol . 205, 181-183 (1963) . G . J . FUHRMAN and F . A . FUHRMAN, Am . J . Physiol . 207, 849-852 (1964) . F . A . FIJHRMAN and G . J . F[THRMAN, Am . J . Physiol . 210, 1225-1228 (1966) . H . MOHRI and R . A . ME1tENDINO, Surgery of the Chest , p . 643, W . B . SAULADERS (1969) . W . J . CROZIER, J . of Gen . Phys . 7, 189-216 {1925) . A . E . STEARN, Adv . i n Enzymology9, 25-74 (1949) .

Glucose metabolism in the hypothermic perfused rat heart.

LIFE SCIENCES Dol . 20, pp,597-608, 1977 . Printed in the U .S .A . ~ergAmoa Pxese GLUCOSE METABOLISM IN THE HYPOTHERMIC PERFUSSD RAT HEART S . Rirb...
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