Metabolism in the hypothermically perfused dog kidney. Incorporation rate of leucine and threonine into proteins

The incorporation of [14C]leucine and [14C]threonine into kidney cortex proteins was studied during 6 days' hypothermic perfusion of dog kidneys at 8-10 degrees C and during in vitro incubation of dog kidney cortex slices at 37 degrees C. Leucine carbon was incorporated into proteins at a higher rate than threonine carbon both during in vitro incubation of kidney cortex slices and during hypothermic kidney perfusion. The incorporation of leucine and threonine during hypothermic perfusion was linear for 6 days but 50-100 times lower than the incorporation of leucine and threonine in kidney cortex slices at 37 degrees C. During hypothermic perfusion there was a decrease in specific activity of leucine and threonine in the perfusate corresponding to a degradation of proteins which was greater than protein synthesis as calculated from the incorporation of label into proteins. Leucine carbon was recovered in CO2 during hypothermic perfusion and in vitro incubation of kidney cortex slices at 37 degrees C. The incorporation of threonine carbon into CO2 was about 10% of the corresponding value for leucine both during hypothermic kidney perfusion and during in vitro incubation of kidney cortex slices at 37 degrees C. It is concluded that there is a turnover of kidney proteins during hypothermic perfusion with a perfusate containing amino acids.     

Interactions between hypothermia and the latency to ischemic depolarization: implications for neuroprotection

BACKGROUND: The authors postulated that hypothermic neuroprotection can be attributed to a delayed onset of ischemic depolarization. METHODS: Halothane-anesthetized rats were prepared for near-complete forebrain ischemia. Direct current (DC) potential microelectrodes were placed in hippocampal CA1. The pericranial temperature was maintained at 31 degrees C, 33 degrees C, 35 degrees C, or 37 degrees C (n = 6 per group). Bilateral carotid occlusion with systemic hypotension was initiated for 10 min. The time to onset of the DC shift was recorded. In a second experiment, rats were assigned to 37 degrees C or 31 degrees C for 10 min of ischemia, or to 31 degrees C for 14 min of ischemia (n = 8 per group). These durations of ischemia were defined to allow 9 min of ischemic depolarization in the 37 degrees C-10 min and 31 degrees C-14 min groups. Neurologic and histologic outcomes were examined 7 days later. RESULTS: Hippocampal CA1 time to depolarization increased with decreasing temperature (P < 0.0001). Time to depolarization was increased by approximately 4 min in the rats maintained at 31 degrees C compared with those at 37 degrees C. Time to repolarization during reperfusion was not affected by temperature. Increasing the duration of ischemia from 10 min to 14 min with the pericranial temperature maintained at 31 degrees C resulted in a duration of depolarization that was equivalent in the 37 degrees C-10 min and 31 degrees C-14 min groups. However, hippocampal CA1 damage was not increased (31 degrees C-10 min = 4 +/- 1% dead neurons; 31 degrees C-14 min = 6 +/- 1% dead neurons, 95% CI, -1% to 3%; 37 degrees C-10 min = 90 +/- 17% dead neurons). CONCLUSIONS: Despite similar durations of DC depolarization, outcome in hypothermic rats was markedly improved compared with normothermic rats. This indicates that hypothermic neuroprotection can be attributed to mechanisms other than the delay in time to onset of ischemic depolarization.     

Solitary scapula mass: atypical presentation of esophageal adenocarcinoma

The stability of adenosine in various diluents in polypropylene syringes and polyvinyl chloride (PVC) bags at three temperatures was studied. Portions of pooled undiluted adenosine infusion (3 mg/ mL) were stored in 60-mL capped syringes, 20 for each storage condition. Adenosine infusions were prepared by mixing adenosine with 5% dextrose injection, 0.9% sodium chloride injection, lactated Ringer's injection, or 5% dextrose and lactated Ringer's injection to produce a concentration of 0.75 mg/mL. Samples of each infusion were stored in 60-mL capped syringes and 50-mL bags, 20 syringes and 20 bags for each storage condition. Syringes and bags were stored in the dark at 25, 5, and -15 degrees C. At various sampling times, three syringes and three bags of each infusion were removed for visual inspection, pH measurement, and high-performance liquid chromatographic analysis. At 10 and 16 days, fungal growth at 25 degrees C was suspected in the infusions prepared with 5% dextrose injection. For all other samples, there was no evidence of precipitation or change in pH. The concentration of adenosine remained constant in all samples at all storage conditions. Adenosine 3 mg/mL was stable in polypropylene syringes for 7 days at 25 degrees C, 14 days at 5 degrees C, and 28 days at -15 degrees C; adenosine 0.75 mg/ mL in 0.9% sodium chloride injection and in 5% dextrose injection was stable in polypropylene syringes and PVC bags for 16 days at 25, 5, and -15 degrees C; and adenosine 0.75 mg/mL in lactated Ringer's injection and in 5% dextrose and lactated Ringer's injection was stable in syringes and bags for 14 days at 25, 5, and -15 degrees C.     

Differential expression of CD14, CD36 and the LDL receptor on human monocyte-derived macrophages. A novel cell culture system to study macrophage differentiation and heterogeneity

Multiple heterogeneous groups of subjects (both sexes and a wide range of maximal oxygen uptake VO2max, body mass, body surface area (AD),% body fat, and AD/mass coefficient) exercised on a cycle ergometer at a relative (%VO2max, REL) or an absolute (60 W) exercise intensity in a cool (CO 21 degrees C, 50% relative humidity), warm humid (WH 35 degrees C, 80%) and a hot dry (HD 45 degrees C, 20%) environment. Rectal temperature (Tre) responses were analysed for the influence of the individual's characteristics, environment and exercise intensity. Exposures consisted of 30-min rest, followed by 60-min exercise. The Tre was negatively correlated with mass in all conditions. Body mass acted as a passive heat sink in all the conditions tested. While negatively correlated with VO2max and VO2max per kilogram body mass in most climates, Tre was positively correlated with VO2max and VO2max per kilogram body mass in the WH/REL condition. Thus, when evaporative heat loss was limited as in WH, the higher heat production of the fitter subjects in the REL trials determined Tre and not the greater efficiency for heat loss associated with high VO2max. Body fatness significantly affected Tre only in the CO condition, where, with low skin blood flows (measured as increases in forearm blood flow), the insulative effect of fat was pronounced. In the warmer environments, high skin blood flows offset the resistance offered by peripheral adipose tissue. Contrary to other studies, Tre was positively correlated with AD/mass coefficient for all conditions tested. For both exercise types used, being big (a high heat loss area and heat capacity) was apparently more beneficial from a heat strain standpoint than having a favourable AD/mass coefficient (high in small subjects). The total amount of variance in Tre responses which could be attributed to individual characteristics was dependent on the climate and the type of exercise. Though substantial for absolute exercise intensities (52%-58%) the variance explained in Tre differed markedly for relative intensities: 72% for the WH climate with its limited evaporative capacity, and only 10%-26% for the HD and CO climates. The results showed that individual characteristics play a significant role in determining the responses of body core temperature in all conditions tested, but their contribution was low for relative exercise intensities when evaporative heat loss was not restricted. This study demonstrated that effects of individual characteristics on human responses to heat stress cannot be interpreted without taking into consideration both the heat transfer properties of the environment and the metabolic heat production resulting from the exercise type and intensity chosen. Their impact varies substantially among conditions.     

Temperature-dependent cardioprotection of exogenous substrates in long-term heart preservation with continuous perfusion: twenty-four-hour preservation of isolated rat heart with St. Thomas' Hospital solution containing glucose, insulin, and aspartate

BACKGROUND AND METHODS: Using an isolated working rat heart model, we determined the effects of glucose, insulin, and aspartate on recovery of cardiac function when used as components of preservation solution at different temperatures. After measurement of baseline cardiac function, hearts (n = 6 per group) were perfused with oxygenated St. Thomas' Hospital solution containing (1) vehicle, glucose (9 mmol/L) or aspartate (20 mmol/L) for 12 hours at either 20 degrees or 4 degrees C; (2) glucose or glucose + insulin (10 U/L) at 20 degrees C for 20 hours; and (3) glucose + insulin at 20 degrees C or glucose + insulin + aspartate at either 20 degrees or 4 degrees C for 24 hours. Cardiac function was measured after preservation and expressed as a percentage of baseline values. RESULTS: At 20 degrees C, both glucose and aspartate increased recovery of cardiac output (vehicle, 57.7% +/- 3.8%; glucose, 76.5% +/- 2.4% [p < 0.05 versus vehicle]; aspartate, 79.9% +/- 1.4% [p < 0.05 versus vehicle]). At 4 degrees C, glucose decreased recovery of cardiac output, whereas aspartate did not change the value (vehicle, 74.4% +/- 2.2%; glucose, 61.4% +/- 2.8% [p < 0.05 versus vehicle]; aspartate, 80.5% +/- 1.7%). The addition of insulin to glucose increased recovery of cardiac output (glucose, 24.6% +/- 4.0%; insulin + glucose, 69.2% +/- 2.0%: p < 0.05). The combined use of these three agents showed an additive effect in improvement of recovery of cardiac output at 20 degrees C (glucose + insulin, 64.2% +/- 2.2%; glucose + insulin + aspartate, 76.0% +/- 1.1%; p < 0.05), but the recovery at 4 degrees C (63.1% +/- 1.8%) was significantly lower than at 20 degrees C. CONCLUSIONS: These results suggest that glucose and aspartate afford differential cardioprotective effects depending on the temperature of the preservation solution and that combined use of glucose, insulin, and aspartate at the optimal temperature may extend graft preservation time.     

Physiological responses of men and women during exercise in hot environments with equivalent WBGT

Eight Japanese men and women participated in this study. They were randomly exposed to two environments: hot-dry; HD (Ta = 40 degrees C, rh 30%, wet bulb globe temperature (WBGT) = 32 degrees C) and hot-wet; HW (Ta = 31 degrees C, rh = 80%, WBGT = 32 degrees C) for 110 min. During the exposure, they rested on a bicycle ergometer for 20 min during rest and 30 min during recovery, then they pedaled it with an intensity of 40% VO2 max for 60 min. Tre, Tsk, and HR were recorded every minute. Total sweat loss and dripping were measured by independent bed balances which was connected to a computer processing with an accuracy of 1 g throughout the experiment. Sweat sodium concentration at forearm and back sites were collected by sweat capsule technique. These results showed that delta Tre, Tsk, evaporated sweat, dripping sweat, body heat storage of both sexes in HD were significantly higher than these in HW during exercise. HR of men in HD at the end of recovery was slightly higher than that of women. Whereas the sweat sodium concentration at forearm and back sites in both sexes remained unchanged either in HD or HW environment, it was found that HD was more stressful than HW environment under equivalent WBGT.     

Clinical implications of penicillin and ceftriaxone resistance among children with pneumococcal bacteremia

BACKGROUND: The influence of non-ionic osmols on thermoregulation is unclear. HYPOTHESIS: Hyperglycemia will attenuate the rise in exercise core temperature. METHODS: Dehydrated by 4-h of water immersion (34.5 degrees C) to the neck, 6 men, (35+/-SD 7 yr) participated in each of three trials where 2.0 g x kg(-1) body wt of oral glucose (33.8% weight per volume) was consumed followed by 80 min supine rest (Glu/Rest), or 70 min supine cycle exercise at 62.8%+/-SE 0.5% (1.97+/-0.02 L x min(-1)) peak O2 uptake, followed by 10 min supine recovery with prior (Glu/Ex) or without glucose (No Glu/Ex) ingestion. Blood samples were taken periodically for measurement of Hb, Hct, Na+, K+, Osm, and glucose; mean skin (Tsk) and rectal (Tre) temperatures, and sweating rate (resistance hygrometry) and skin blood velocity (laser Doppler) were measured intermittently. RESULTS: Mean percent changes in plasma volume (p<0.05) for the exercise trials were not different: -12.3+/-2.2% (No Glu/Ex) and -12.1+/-2.1% (Glu/Ex). Mean (+/-SE) pre-exercise plasma [glucose] for Glu/Ex was higher than that of No Glu/Ex (108.4+/-3.9 vs. 85.6+/-1.6 mg x dL(-1), respectively, p<0.05). Glu/Ex vs. No Glu/Ex data, respectively, at the end of exercise indicated that: Tre was lower by 0.4 degrees C (38.2+/-0.2 vs. 38.6+/-0.1 degrees C, p<0.05), Tsk was lower (32.0+/-0.3 vs. 32.4+/-0.2 degrees C, p<0.05), forearm sweating rate was lower (0.94+/-0.09 vs. 1.05+/-0.07 mg x cm(-2) x min(-1), p<0.05); and head (temporal) skin blood velocity was not different (1.67+/-0.21 vs. 1.51+/-0.24 Hz x 10(3), NS). CONCLUSIONS: Elevation of plasma [glucose] prior to supine submaximal exercise in dehydrated men attenuates the increase of Tre without alteration of heat production, total body sweating, serum electrolytes and osmolality, or exercise-induced hypoglycemia: the mechanism may be enhanced peripheral blood flow that could enhance body heat loss.     

The vitamin B 6 requirements of the laying hen for reproduction

Some parameters related to withstanding severe cold (-20 degrees C) after administration of increasing doses of ethanol were investigated using guinea-pigs. The animals had been reared either at 22-23 degrees C or at 17-18 degrees C. They received ethanol in doses of 0.8 g, 1.2 g, 1.4 g or 1.6 g per kg of body weight. The fall of rectal temperature and its level at death were registered. The survival time, ethanol concentration in the blood and the brain, serum glucose and serum FFA at death were determined. In the animals reared at 22-23 degrees C the ethanol doses of 1.2-1.6 g/kg caused a significant shortening of the survival time and accelerated the fall of the rectal temperature. In addition the rectal temperature at death after ethanol was lower than in the controls. In the animals reared at 17-18 degrees C the ethanol doses used did not have any significant effect on the survival time and the rectal temperature. In both groups, ethanol concentration in the brain was lower (about 20-40%) than in the blood, the difference being greater in the group reared at 22-23 degrees C. Ethanol had no effect on the glucose concentrations. Serum FFA levels were slightly lower in animals reared at 22-23 degrees C than in those grown in the cooler temperature. It became evident that ethanol has a dose dependent deleterious effect on the thermoregulation of animals reared in warm (22-23 degrees C). The effect was seen at and above the dose of 1.2 g/kg. The results indicate further even a slight acclimation to cold was able to abolish the effect of these rather great doses of ethanol in severe cold exposure.     

Reversible and irreversible glucose disposal in dogs: influence of fasting and cold exposure

Rates of total glucose entry rate, irreversible loss, and recycling were measured in unanesthetized dogs with indwelling arterial and venous catheters. Four experimental conditions were selected: 16 or 26 hr of fasting and neutral (+25 degrees C) or cold (-21 degrees C) ambient temperatures. A mixture of U 14C-glucose and 2-3H-glucose was used as a tracer, according to the primed infusion technique. No matter what the ambient temperature was, increase of fasting time from 16 to 26 hr induced a slight, but nonsignificant, decrease in both the total glucose entry rate and the irreversible loss. At neutral ambient temperature, the amount of glucose promptly recycled was less after 16 hr than after 26 hr of fasting, while an opposite pattern was observed during cold exposure. Thus, that part of hepatic glucose entry promptly recycled was significantly increased from 22% (16 hr of fasting) to 31% (26 hr of fasting) at neutral ambient temperature. It remained almost unchanged (20% and 18%) in cold. It was, therefore, suggested that this increase might be considered as an compensatory mechanism, exerting a sparing effect on glucose utilization. This mechanism does not occur in cold ambient temperature, thus, worsening a possible shortage in glucose supply.     

Physiopathology of bedsores

Listeria monocytogenes is a food-borne pathogenic bacterium that can be found in soft cheese. At the beginning of cheese ripening, the pH is about 4.85-4.90. The aim of this work was to study the influence of temperature, preincubation temperature (temperature at which the inoculum was cultivated) and initial bacterial concentration on the survival of L. monocytogenes (strain Scott A) at pH 4.8. It was demonstrated in an earlier study that these factors did influence growth kinetics. Survival studies of L. monocytogenes were done in a laboratory broth simulating cheese composition. Four test temperatures (2, 6, 10 and 14 degrees C) and two preincubation temperatures were studied (30 degrees C or the test temperature). Listeria monocytogenes (strain Scott A) was unable to grow at pH 4.8 under all conditions tested. The time for 10% survival was about 11 and 2 d, at 2 degrees C with preincubation at 2 degrees C and 30 degrees C, respectively; 9 d at 6 degrees C with preincubation at 6 degrees C; 4 d at 6 degrees C with preincubation at 30 degrees C; and 1 d at 14 degrees C with preincubation at 14 degrees C or at 30 degrees C. The results show that survival of L. monocytogenes (strain Scott A) at pH 4.8 is not dependent on initial bacterial concentration but on both the test and preincubation temperatures.     

Pyruvate reverses fatty-acid-induced depression of ventricular function and calcium overload after hypothermia in guinea pig hearts

OBJECTIVE: High levels of free fatty acids have been shown to impair mechanical recovery and calcium homeostasis of isolated rat hearts following hypothermic perfusion. The objective of the present study was to investigate whether inhibition of fatty acid oxidation through activation of pyruvate dehydrogenase by millimolar concentrations of pyruvate could influence functional recovery and Ca2+ homeostasis after a hypothermic insult. METHODS: Ventricular function and myocardial calcium ([Ca]total) were measured in 3 different groups of Langendorff-perfused guinea pig hearts exposed to 40 min hypothermic (15 degrees C) perfusion, followed by 30 min rewarming at 37 degrees C. The hearts were perfused with either 11.1 mM glucose (G), glucose and 1.2 mM palmitate (GP), or glucose, palmitate and 5 mM pyruvate (GPP) as energy substrates. RESULTS: All groups showed marked elevations in [Ca]total during hypothermia (from 0.6-0.7 mumol.g dry wt-1 to 9.3-12.2 mumol.g dry wt-1 at 40 min hypothermia, P < 0.05), associated with a pronounced increase in left ventricular end-diastolic pressure (LVEDP from 0-2 to 50-60 mmHg). Following rewarming, GP-perfused hearts showed significantly lower recovery of mechanical function compared to both G- and GPP-perfused hearts (% recovery of left ventricular developed pressure: 27 +/- 8 vs. 62 +/- 3 and 62 +/- 8%, respectively, P < 0.05). The reduced mechanical recovery of GP-perfused hearts was associated with elevated [Ca]total. In separate experiments we found that addition of 1.2 mM palmitate reduced glucose oxidation ([14C]glucose) from 1.77 +/- 0.28 mumol.min-1.g dry wt-1 (G-perfused hearts) to 0.15 +/- 0.04 mumol.min-1.g dry wt-1 (GP-perfused hearts, P < 0.05), implying that fatty acids had become the major substrate for oxidative phosphorylation. Fatty acid oxidation was, however, less pronounced after further addition of 5 mM pyruvate. Thus, palmitate oxidation ([3H]palmitate) was more than 40% lower in GPP-perfused than in GP-perfused hearts (0.83 +/- 0.22 vs. 1.41 +/- 0.12 mumol.min-1.g dry wt-1, P < 0.05). CONCLUSIONS: The present results demonstrate impaired ventricular function and calcium homeostasis after hypothermia in guinea pig hearts perfused with fatty acids in addition to glucose, as compared to hearts perfused with glucose alone. Furthermore, we show that these unfavourable effects of fatty acids can be overcome by an exogenous supply of pyruvate.     

Induction of tolerance to hypothermia and hyperthermia by a common mechanism in mammalian cells

Pretreatment by hypothermic (25 degrees C) cycling (PHC) of attached exponential-phase V79 Chinese hamster cells by Method 4 (24 hr at 25 degrees C + 1.5 hr at 37 degrees C + 24 hr at 25 degrees C + trypsin + 3 hr at 37 degrees C) or by Method 3 (48 hr at 25 degrees C + trypsin + 3 hr at 37 degrees C) make mammalian V79 cells significantly more resistant to 43 degrees C hyperthermia. There is no significant difference in the 43 degrees C curves whether Method 3 or 4 is used for pre-exposure. If pre-exposure at 15 or 10 degrees C, the resistance to hyperthermia is significantly reduced. PHC by Method 4 significantly increases survival of cells exposed to 5 degrees C and, to a lesser extent, to 10 degrees C. The increase in hyper- and hypothermic survival after PHC cannot be accounted for by changes in cell cycle distribution. Heat-shock protein synthesis is not induced by PHC; hence, protection does not result from newly synthesized proteins. When cells are made tolerant to hyperthermia by a pretreatment in 2% DMSO for 24 hr at 37 degrees C (Method 8), the cells are not more resistant to subsequent exposures to hypothermia, either at 5 or 10 degrees C. The results imply that there may be two mechanisms of inducing resistance to hyperthermia, only one of which also confers resistance to hypothermia.     

Terson''s syndrome in a patient with acute promyelocytic leukemia on all-trans retinoic acid treatment

Hypothermia induced by surface cooling has shown to protect vulnerable regions of the brain during an ischemic insult. This study evaluated the neuroprotective efficacy of neurotensin, a potent hypothermic agent, using a 5-min carotid occlusion procedure in the gerbil. In Experiment 1, the dose-response and time course of neurotensin-induced hypothermia were evaluated (n = 5/dose). Central infusion of 10, 20, and 30 micrograms neurotensin were found to significantly decrease core body temperature of conscious gerbils within 30 min of administration. In Experiment 2, gerbils pretreated with 30 micrograms neurotensin were permitted to become hypothermic or were maintained at 37 degrees-38 degrees C (rectal) during ischemic insult. Other gerbils were pretreated with peptide vehicle prior to ischemic insult (at 37 degrees -38 degrees C) or underwent a sham procedure (n = 6/condition). At 24 h after surgery, gerbils were tested for increased locomotor activity in an open-field apparatus. Gerbils pretreated with peptide vehicle or neurotensin and maintained at 37 degrees-38 degrees C during ischemia had significantly higher activity levels compared to the other treated groups. In contrast, gerbils made hypothermic with neurotensin exhibited activity levels similar to sham gerbils. Histological assessment revealed that neurotensin-induced hypothermia protected the CA1 region from ischemic damage.     

Cerebral oxygenation during cardiopulmonary bypass in children

OBJECTIVE: Previous work has found cerebral oxygen extraction to decrease during hypothermic cardiopulmonary bypass in children. To elucidate cardiopulmonary bypass factors controlling cerebral oxygen extraction, we examined the effect of perfusate temperature, pump flow rate, and hematocrit value on cerebral hemoglobin-oxygen saturation as measured by near infrared spectroscopy. METHODS: Forty children less than 7 years of age scheduled for cardiac operations with continuous cardiopulmonary bypass were randomly assigned to warm bypass, hypothermic bypass, hypothermic low-flow bypass, or hypothermic low-hematocrit bypass. For warm bypass, arterial perfusate was 37 degrees C, hematocrit value 23%, and pump flow 150 ml/kg per minute. Hypothermic bypass differed from warm bypass only in initial perfusate temperature (22 degrees C); hypothermic low-flow bypass and low-hematocrit bypass differed from hypothermic bypass only in pump flow (75 ml/kg per minute) and hematocrit value (16%), respectively. Cerebral oxygen saturation was recorded before bypass (baseline), during bypass, and for 15 minutes after bypass had been discontinued. RESULTS: In the warm bypass group, cerebral oxygen saturation remained at baseline levels during and after bypass. In the hypothermic bypass group, cerebral oxygen saturation increased 20% +/- 2% during bypass cooling (p < 0.001), returned to baseline during bypass rewarming, and remained at baseline after bypass. In the hypothermic low-flow and hypothermic low-hematocrit bypass groups, cerebral oxygen saturation remained at baseline levels during bypass but increased 6% +/- 2% (p = 0.05) and 10% +/- 2% (p < 0.03), respectively, after bypass was discontinued. CONCLUSIONS: In children, cortical oxygen extraction is maintained during warm cardiopulmonary bypass at full flow and moderate hemodilution. Bypass cooling can decrease cortical oxygen extraction but requires a certain pump flow and hematocrit value to do so. Low-hematocrit hypothermic bypass and low-flow hypothermic bypass can also alter cortical oxygen extraction after discontinuation of cardiopulmonary bypass.     

Thermoregulatory effects of monoamine potentiators and inhibitors in the rat

Exogenously administered monoamines may elicit variable thermoregulatory responses dependent on dosage, species, site of administration, ambient temperature, etc. In an attempt to reconcile several inconsistencies, we have undertaken a series of studies related to monoaminergic control of temperature regulation. Thus, intraventricular administration of serotonin (2.64-26.4 mug) and norepinephrine (3.3-32.8 mug) in rats evoked acute (15-60 min) dose-dependent hypothermic responses (delta Tre = 2 degrees C) that were gradually superseded by significant, more persistent hyperthermia (delta Tre = 1 degreee C). Administration of chlorimipramine or imipramine (total dose 40 mug), even in monoamine-depleted animals, caused long-lasting hyperthermic responses, presumably by the prevention of reuptake of serotonin and norepinephrine at nerve terminals involved in thermoregulation. Pretreatment with the serotonin inhibitor cyproheptadine (4o mug) attenuated the hyperthermia achieved by central administration of chlorimipramine alone. We conclude that both monoamines can act as thermogenic agents under the conditions of these experiments.     

Determination of optimum retrograde cerebral perfusion conditions

Retrograde cerebral perfusion through a superior vena caval cannula is a new technique used to protect the brain during operations on the aortic arch. We measured cerebral tissue blood flow, oxygen consumption, and cerebrospinal fluid pressure under various perfusion conditions in hypothermic (20 degrees C) mongrel dogs (n = 18, 12.8 +/- 0.6 kg) to determine the optimum conditions for retrograde cerebral perfusion. Retrograde cerebral perfusion was performed by infusion via the superior vena caval cannula and drainage via the ascending aortic cannula while the inferior vena cava and azygos vein were clamped. Retrograde cerebral perfusion was performed as the external jugular venous pressure was changed from 15 to 35 mm Hg in increments of 5 mm Hg. Cerebral tissue blood flow was measured by the hydrogen clearance method. Hypothermic retrograde cerebral perfusion with an external jugular venous pressure of 25 mm Hg provided about half the cerebral tissue blood flow of hypothermic (20 degrees C) cardiopulmonary bypass with a flow rate of 1000 ml/min (13.7 +/- 7.9 versus 32.7 +/- 8.5 ml/min per 100 gm). It decreased significantly as the external jugular venous pressure was decreased from 25 to 15 mm Hg but did not increase significantly as the external jugular venous pressure was increased from 25 to 35 mm Hg. Whole-body oxygen consumption during hypothermic retrograde cerebral perfusion with an external jugular venous pressure of 25 mm Hg was one quarter of that during hypothermic cardiopulmonary bypass (3.4 +/- 0.7 versus 12.7 +/- 5.6 ml/min) and varied in proportion to external jugular venous pressure. The cerebrospinal fluid pressure was a little lower than the external jugular venous pressure (19.2 +/- 4.5 mm Hg versus 24.8 +/- 2.4 mm Hg) but also varied with the external jugular venous pressure. The cerebrospinal fluid pressure remained lower than 25 mm Hg so long as the external jugular venous pressure remained lower than 25 mm Hg. High external jugular venous pressure was associated with high intracranial pressure, which restricts cerebral tissue blood flow and may cause brain edema. We believe that a venous pressure of 25 mm Hg is the optimum condition for retrograde cerebral perfusion.     

Success rate of cytogenetic analysis at the time of second-trimester dilation and evacuation

Hypoxia elicits a number of compensatory responses in animals, including behavioral hypothermia. The hypothesis that hypoglycemia induces hypothermia in the bullfrog Rana catesbeiana was tested and that this behavioral response would be beneficial. Frogs equipped with a temperature probe were tested in a thermal gradient (10-40 degrees C). Insulin (15 IU kg-1) caused significant reduction of body temperature, from 25.0 to 17.8 degrees C. A non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG, 50 mg kg-1), which blocks intracellular glucose utilization, was also injected and caused a similar drop in body temperature, despite an increase in plasma glucose levels. To assess the possible benefits of hypoglycemia-induced hypothermia, the effects of insulin and 2-DG injections were measured on plasma glucose concentration and on oxygen consumption of frogs equilibrated at 10, 20 and 30 degrees C. The plasma glucose was elevated at higher temperatures and so was oxygen consumption. The insulin caused a significant reduction of plasma glucose concentration (about 1.22 muMol ml-1) whereas 2-DG caused a significant increase (about 0.70 muMol ml-1) at 30 degrees C. Both drugs caused a reduction of oxygen consumption (approximately 0.388 and 0.382 ml min-1 kg at 30 degrees C after insulin and 2-DG injection, respectively). No effect of either insulin or 2-DG was observed when the animals were equilibrated at 10 degrees C. In conclusion, hypothermia may be a beneficial response to hypoglycemia in frogs.     

Comparison of brain tissue metabolic changes during ischemia at 35 degrees and 18 degrees C

BACKGROUND: We evaluated brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2) and pH during ischemia with brain temperature at 35 degrees and 18 degrees C in the same patient. METHODS: Surgery was performed in a 60-year-old woman to clip a large aneurysm in the left internal carotid artery (ICA). A Paratrend 7 probe measuring PO2, PCO2, and pH was inserted into tissue at risk for ischemia during ICA occlusion and brain protection was provided with 9% desflurane. One week later, hypothermic circulatory arrest with brain temperature at 18 degrees C was performed for aneurysm clipping and tissue measurements were obtained during ischemia and rewarming. RESULTS: At 35 degrees C, ICA occlusion for 16 minutes produced tissue hypoxia (PO2 = 0) and acidosis (pH = 6.70). The rate of increase of hydrogen ion (H+) reached 50 nEq.L(-1).min(-1) during ICA occlusion and there was a slow recovery of acidosis at the end of the ischemic period. During hypothermic circulatory arrest, tissue PO2 was sensitive to decreases in blood pressure and decreased rapidly during exsanguination. Although tissue pH decreased to 6.5 with 30 min of no pump flow, the rate of H+ increase during hypothermic arrest was one-third of that seen during ischemia at 35 degrees C. During rewarming from profound hypothermia, two phases of recovery from acidosis were observed, one during CO2 clearance and one after tissue reoxygenation. Recovery of acidosis occurred sooner at 18 degrees C than at 35 degrees C. CONCLUSIONS: These results show that tissue acidosis develops more slowly and recovers more rapidly with hypothermic ischemia. This may be an important mechanism of reduced ischemic injury during hypothermia.     

Characterization of recombinant E. coli ATCC 11303 (pLOI 297) in the conversion of cellulose and xylose to ethanol

This work describes the characterization of recombinant Escherichia coli ATCC 11303 (pLOI 297) in the production of ethanol from cellulose and xylose. We have examined the fermentation of glucose and xylose, both individually and in mixtures, and the selectivity of ethanol production under various conditions of operation. Xylose metabolism was strongly inhibited by the presence of glucose. Ethanol was a strong inhibitor of both glucose and xylose fermentations; the maximum ethanol levels achieved at 37 degrees C and 42 degrees C were about 50 g/l and 25 g/l respectively. Simultaneous saccharification and fermentation of cellulose with recombinant E. coli and exogenous cellulose showed a high ethanol yield (84% of theoretical) in the hydrolysis regime of pH 5.0 and 37 degrees C. The selectivity of organic acid formation relative to that of ethanol increased at extreme levels of initial glucose concentration; production of succinic and acetic acids increased at low levels of glucose (< 1 g/l), and lactic acid production increased when initial glucose was higher than 100 g/l.     

Effects of varying levels of duodenal or midjejunal glucose and 2-deoxyglucose infusion on small intestinal disappearance and net portal glucose flux in steers

Six crossbred steers (261 +/- 18 kg BW) fitted with hepatic portal, mesenteric venous and arterial catheters, and duodenal, midjejunal, and ileal cannulas were used in a replicated 3 x 3 Latin square design to determine the effect of varying levels and site of glucose plus 2-deoxyglucose (2DG) infusion on net portal-drained visceral flux. Steers were fed chopped alfalfa in six equal portions daily at 1.5% of BW. Glucose (0, 9, or 18 g/h) and 2DG (0, 1, or 2 g/h) were infused continuously through the duodenal or midjejunal cannula (two infusion sites) at total glucose plus 2DG infusion rates of 0, 10, or 20 g/h. Arterial and portal blood samples were taken simultaneously at 20-min intervals from 5 to 9 h of infusion. Portal blood flow was determined by continuous infusion of p-aminohippurate and net flux was calculated as venous-arterial concentration (PA) difference times blood flow. Arterial concentration of glucose was not affected (P > .10) by glucose plus 2DG infusion, whereas arterial concentration of 2DG was greater (P < .05) when glucose plus 2DG was infused into the duodenum and increased (linear, P < .10) as amount of glucose plus 2DG infused into both the duodenum and midjejunum increased. Net portal flux and PA difference of glucose and 2DG were greater (P < .05) when glucose plus 2DG was infused into the duodenum. Although 2DG was infused at 10% of the total glucose plus 2DG infusion, it accounted for only 1.7 and .7% of the glucose plus 2DG appearing in portal blood when glucose plus 2DG was infused at 10 and 20 g/h, respectively. We conclude that glucose is more readily absorbed across the proximal-half than the distal-half of the small intestine, and that passive diffusion is a minor route of glucose absorption.