Arteriovenous Lactate Difference Research Articles

Cerebral utilization of glucose, ketone bodies and oxygen in starving infant rats and the effect of intrauterine growth retardation.

Cerebral arteriovenous differences of acetoacetate, D-beta-hydroxybutyrate, glucose, lactate and oxygen and brain DNA content was measured at 20 days of age in intrauterine growth retarded (IUGR) rats and normal littermates after 48 and 72 h of starvation. Cerebral blood flow (CBF) was measured with labeled microspheres in other comparable groups of IUGR and control rats. CBF was similar in IUGR and normal littermates (0.57+/-0.09 and 0.58+/-0.10 ml/min respectively). After 48 h of starvation, arterial glucose was significantly lower in IUGR than control animals but the arterial concentrations of ketone bodies were similar. After 48 h of starvation, cerebral arteriovenous difference of beta-hydroxybutyrate was significantly higher in control than IUGR rats also when expressed per mg brain DNA as was the fractional uptake of D-beta-hydroxybutyrate. After 72 h of starvation, arterial concentrations of ketone bodies were significantly lower in IUGR rats than controls but the fractional uptake of D-beta-hydroxybutyrate was increased compared to IUGR rats starved for 48 h. The average percentage of calculated total substrate uptake (mumol/min) accounted for by ketone bodies increased in control animals from 31.1% after 48 h of starvation to 41.0% after 72 h of starvation. In IUGR rats these percentage values were 26.5 and 25.7 respectively. After 72 h of starvation the fraction of total cerebral uptake of substrates accounted for by ketone bodies was significantly higher in control that IUGR rats. As total cerebral uptake of substrates was similar between IUGR and control animals it is concluded that IUGR rats are more dependent on glucose as a substrate for the brain during starvation.

Some aspects of foetal and uteroplacental metabolism in cows with indwelling umbilical and uterine vascular catheters.

1. The experiments were carried out on conscious pregnant Jersey cows with intravascular catheters implanted during late gestation in umbilical and uterine vessels. All but three of fifteen animals delivered live healthy calves. 2. Rountine daily analyses were made of blood gas tensions, pH and packed cell volume in foetal and maternal blood; plasma concentrations of glucose, fructose, lactate and urea were also determined. Measurements of plasma free fatty acids and blood acetate concentrations were made less frequently. Foetal heart rate and arterial blood pressure were recorded in animals with an umbilical arterial catheter. 3. The concentration differences between foetal and maternal blood or plasma in glucose, urea and acetate were measured in fifteen animals. The maternal-to-foetal glucose and acetate gradients across the placenta were high while the foetal-to-maternal plasma urea differences were small. 4. In those animals with patent arterial and venous catheters, uterine and umbilical blood flows were measured together with the arteriovenous differences in 02, glucose, acetate and lactate so that rates of foetal and uterine consumption could be estimated. The rates of utilization of O2, glucose and acetate by the foetus were lower than the values for the whole uterus, while the uteroplacental metabolism of these substrates was very high. 5. Significant amounts of lactate, which appeared to be produced by the uteroplacental tissue, were utilized by the foetus; the remainder passed into the uterine venous blood. 6. The total substrate/O2 quotient for the foetus, calculated from the utilization of known metabolites, appeared to be greater than 1. Thus, in the calf some carbon accumulation from sources other than amino acids, the uptake of which was not measured, would seem to occur. These results and the metabolic activity of the uterine tissues are discussed in relation to comparable findings in the sheep.

Utilization of oxidizable substrates by the sheep hind limb: Effects of starvation and exercise

Measurements of substrate uptake by the sheep hind limb show a pattern similar to human and other monogastric animals. Thus free fatty acids (FFA) are the principal substrates at rest and during exercise while β-hydroxybutyrate and acetoacetate are major nutrients in starved animals. The hind limb has arteriovenous differences for glucose and lactate which indicate that glucose supplies about 27% of the fuel of respiration during exercise, but the hind limb in resting, fed, and starved animals returns essentially all of the glucose carbon to the blood in the form of lactate. This finding is consistent with a conservation of glucose in animals which obtain very little dietary glucose. Although some acetate is extracted from the blood in fed sheep, the utilization of this nutrient can account for only 2% or less of the oxygen uptake in the hind limb of starved or exercising animals. Thus, while acetate is the major product of the sheep rumen it is not used directly as a major energy source. We propose that most of the acetate is converted to FFA which can be stored as triglyceride or oxidized in muscle.

Uptake of lactate by dog skeletal muscle in vivo and the effect of free fatty acids.

These experiments were designed to determine: 1) if lactate can be extracted from the arterial blood and utilized by resting skeletal muscle of the dog, and 2) if lactate uptake or production by skeletal muscle is influenced by the level of circulating free fatty acids. Skeletal muscle arteriovenous differences in lactate were measured at several arterial lactate and free fatty acid concentrations. With sodium pentobarbital anesthesia and a low concentration of free fatty acids, arterial lactate concentrations of 1-2 mM were associated with extraction of lactate; however, when circulating free fatty acids were elevated (greater than 1 mM), no extraction of lactate occurred at these lactate concentrations. The relationship between arterial free fatty acids and uptake or release of lactate demonstrated in these in vivo studies suggest that the inhibition of free fatty acid release from adipose tissue that occurs when the arterial lactate concentration increases may function facilitate the metabolism of lactate by skeletal muscle.

Effect of circulating FFA on lactate production by skeletal muscle during stimulation

The present experiments were undertaken to study the effects of FFA on lactate production by skeletal muscle during stimulation. In the first group, dogs were anesthetized with sodium pentobarbital and given no anticoagulant. The second group was also anesthetized with sodium pentobarbital but in addition given heparin and a fat-albumin infusion to elevate FFA. Stimulating the nerves to a group of skeletal muscles in the hindlimb (1.5/s) increased muscle blood flow 2.4-fold in both groups. In the first group stimulation did not alter the arteriovenous difference of lactate across the muscles. The difference was close to zero before and during stimulation. However in the second group, in which FFA were elevated, stimulation produced a large increase in muscle lactate production. In both groups there were no differences in the L/P ratio of muscle venous blood during stimulation. These results indicate that an increase in lactate production following muscle stimulation is not necessarily related to a state of tissue hypoxia.

Acute cold exposure and the metabolism of blood glucose, lactate and pyruvate, and plasma amino acids in the hind leg of the fed and fasted young ox.

1. Young steers were fed either 3-4 or 20 h before exposure to a thermoneutral or a moderately cold environment. Measurements were made of total oxygen consumption (total V 0-2), respiratory quotient (rq), blood packed cell volume (PCV), and hind-leg blood flow (leg Q) and oxygen uptake (leg VO-2). The arteriovenous differences in whole blood glucose, lactate and pyruvate, and individual amino acid and urea concentrations across the leg were also measured. Net exchange and fractional uptake of these metabolites by the leg were calculated from these results. 2. Cold exposure doubled total VO-2, significantly decreased RQ and significantly increased PCV. Leg Q and leg VO-2 increased 3- to 5-fold and 4- to 13-fold respectively in both feeding groups. Arterial blood glucose increased slightly but significantly in both 20 h- and 3 h-fed steers. There was a substantial increase in mean net leg uptake of glucose in both feeding groups. This was much greater in the 20 h-fed group because of the significant increase in fractional uptake occurring only in this group. Cold did not significantly affect arterial blood lactate or pyruvate levels, but the net leg output of lactate found in both feeding groups in thermoneutrality was increased in the 20 h-fed steers, and reversed to a net uptake in the 3 h-fed animals. Cold caused a small but significant decrease in the total plasma amino acid level in the 20 h-fed but not in the 3 h-fed group; individual amino acid levels or leg uptakes were not affected. 3. Feeding before the experiment caused a significant increase in RQ. Leg Q, leg uptake of glucose and leg output of lactate increased after feeding in the thermoneutral environment only. Arterial pyruvate increased significantly, but net leg output was not significantly affected by feeding. Arterial plasma concentration of several individual, but not of total amino acids, increased significantly in both environments, and the net output of many individual amino acids in the 20 h-fed steers was decreased or reversed to a net uptake in the 3 h-fed group in thermoneutrality only. 4. The results suggest that blood glucose could be a significant fuel for oxidation in shivering skeletal muscle in young steers, and that output of amino acids from skeletal muscle could not contribute significantly to this increased glucose supply by hepatic gluconeogenesis.

Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats.

1. The effects of starvation and diabetes on brain fuel metabolism were examined by measuring arteriovenous differences for glucose, lactate, acetoacetate and 3-hydroxybutyrate across the brains of anaesthetized fed, starved and diabetic rats. 2. In fed animals glucose represented the sole oxidative fuel of the brain. 3. After 48h of starvation, ketone-body concentrations were about 2mm and ketone-body uptake accounted for 25% of the calculated O(2) consumption: the arteriovenous difference for glucose was not diminished, but lactate release was increased, suggesting inhibition of pyruvate oxidation. 4. In severe diabetic ketosis, induced by either streptozotocin or phlorrhizin (total blood ketone bodies >7mm), the uptake of ketone bodies was further increased and accounted for 45% of the brain's oxidative metabolism, and the arteriovenous difference for glucose was decreased by one-third. The arteriovenous difference for lactate was increased significantly in the phlorrhizin-treated rats. 5. Infusion of 3-hydroxybutyrate into starved rats caused marked increases in the arteriovenous differences for lactate and both ketone bodies. 6. To study the mechanisms of these changes, steady-state concentrations of intermediates and co-factors of the glycolytic pathway were determined in freeze-blown brain. 7. Starved rats had increased concentrations of acetyl-CoA. 8. Rats with diabetic ketosis had increased concentrations of fructose 6-phosphate and decreased concentrations of fructose 1,6-diphosphate, indicating an inhibition of phosphofructokinase. 9. The concentrations of acetyl-CoA, glycogen and citrate, a potent inhibitor of phosphofructokinase, were increased in the streptozotocin-treated rats. 10. The data suggest that cerebral glucose uptake is decreased in diabetic ketoacidosis owing to inhibition of phosphofructokinase as a result of the increase in brain citrate. 11. The inhibition of brain pyruvate oxidation in starvation and diabetes can be related to the accelerated rate of ketone-body metabolism; however, we found no correlation between the decrease in glucose uptake in the diabetic state and the arteriovenous difference for ketone bodies. 12. The data also suggest that the rates of acetoacetate and 3-hydroxybutyrate utilization by brain are governed by their concentrations in plasma. 13. The finding of very low concentrations of acetoacetate and 3-hydroxybutyrate in brain compared with plasma suggests that diffusion across the blood-brain barrier may be the rate-limiting step in their metabolism.

Glucose production from fructose.

Five adult subjects, three male and two female, were given fructose-U-C-14 by single injection under the condition of fructose loading. The radioactivity in glucose was determined in serial arterial samples. On a separate day, glucose-6-C-14 was given to these same subjects under identical conditions. Using these two curves, the fructose converted to glucose was determined. In these subjects an average of 30.94 per cent of the infused fructose appeared as blood glucose. Hepatic vein catheterization showed a large positive arteriovenous difference for fructose (50 to 80 per cent of infused fructose) and negative arteriovenous differences for glucose and lactate. There was a discrepancy between the calculated fructose conversion to glucose (30 per cent) from the tracer studies and the glucose production estimated from the hepatic arteriovenous differences of glucose (10 per cent). Supporting data for the validity of the former figure are given. The simultaneous hepatic production of glucose and lactate by the liver is most likely due to the large substrate load of fructose entering the glycolytic scheme at a point which bypasses the rate limiting enzymes for both glycolysis and gluconeogenesis.

Observations on a model of prolifer- ative lung disease. I. Transpulmonary arteriovenous differences of lactate, pyruvate, and glucose.

Intravenous injections of complete Freund's adjuvant, used by others to stimulate the reticuloendothelial system of small laboratory animals, produced granulomas resembling sarcoid in the lung of the dog. At the height of the disease, when granulomas occupied more than half of the alveolar tissues, transpulmonary arteriovenous (A-[unk]V) differences of lactate, pyruvate, and glucose were measured. When the diseased dogs breathed room air, the A-[unk]V differences of lactate and pyruvate were greater than normal; and when the dogs breathed an hypoxic mixture, the differences increased further. Hence the model affords the opportunity for studying the in vivo metabolism of diseased lungs. It may also prove useful for studying other aspects of granulomatous disease which cannot be easily approached in man.

The role of lactic acid in gas secretion in the teleost swimbladder

1. 1. Existing evidence for the mechanism of gas secretion into the swimbladder of fish suggests that lactic acid is produced by the gas gland tissue in the presence of high oxygen pressure and is responsible for the “single concentrating effect” (Kuhn & Kuhn, 1961) which is multiplied by countercurrent blood flow through the rate mirabile to produce the necessary gas pressure. 2. 2. The catabolism of the gas gland tissue of the vermilion rockfish, Sebastodes miniatus, a species whose ecological depth range extends down to 200 m, has been investigated under O 2 pressures up to 51 atm. Lactic acid was produced by the tissue throughout the range of pressures investigated, and no evidence of a Pasteur effect was found. CO 2 production by the tissue was similar and very low under both O 2 and N 2 and suggested that citric acid cycle enzymes and oxidative phosphorylation systems were very weak in this tissue. 3. 3. The maximum glycolytic rates observed were too low to account for pre- and post-rate differences in lactate concentration observed by other workers, and glycogen levels in the gas gland tissue (0·02 mg/mg dry wt.) could produce the observed arteriovenous differences in lactate for only a few minutes. 4. 4. The essential role of lactic acid in gas secretion was supported by injecting oxamic acid, a competitive inhibitor of lactic dehydrogenase, into the swimbladder of deflated fish; statistically significant differences in control and experimental groups in both amounts and relative percentages of gases secreted were observed.

Myocardial lactate metabolism at rest and during exercise in ischemic heart disease

Cardiac dynamics and myocardial extraction of oxygen and lactate were investigated at rest in subjects with normal coronary arteries and in patients with coronary heart disease. Coronary artery disease was considered significant when there was obstruction or more than 50 per cent narrowing of one or more coronary arteries. Half of the patients were also studied during moderate exercise. The hemodynamic findings were almost comparable in all cases. On exercise, in patients with significant coronary disease, there was evidence of abnormal left ventricular function, and increases in cardiac index were mediated through a much higher left ventricular end-diastolic pressure. Coronary arteriovenous difference and the myocardial extraction of oxygen were normal at rest and unchanged on exercise in all cases. Marked rise in the arterial level and a significant increase in the arteriovenous difference of lactate were present in all cases. The extraction ratio of lactate by the myocardium remained normal and increased only slightly in control subjects. However, this ratio increased to normal levels during exercise in all patients with significant coronary artery disease. Possible explanations for the increased coronary arteriovenous difference and myocardial extraction ratio of lactate on exercise in these patients are discussed.

Monitoring cerebral blood flow and oxygen, glucose, lactate and ammonia metabolism.

New application of methods for monitoring cerebral blood flow and cerebral arteriovenous oxygen, glucose, lactate and ammonia differences are described. Results of trials of their validity in monkeys during experimental procedures are described. The apparatus includes infrared gas analyzers for monitoring arteriovenous differences after diffusion of nitrous oxide through silastic, electromagnetic flowmeters for monitoring cerebral venous outflow, the Technicon apparatus for measuring arteriovenous differences for lactate, glucose and ammonia, and the Guyton analyzer for monitoring cerebral arteriovenous oxygen differences. Cerebral blood flow in the monkey measured by the nitrous oxide method was 61 ml/100 g brain per min, cerebral oxygen consumption was 2.8 to 3.35 ml/100 g brain per min, cerebral glucose consumption was 3.52 mg/100 g brain per min, cerebral arteriovenous lactate difference was 1.1 mg/100 ml, cerebral arteriovenous ammonia difference was 2 mg/100 ml. Inhalation of 100% oxygen, 5% CO 2 in air, 20% CO 2 in air and hyperventilation caused no change in cerebral oxygen, glucose, lactate, and ammonia metabolism. During anoxic anoxia, cerebral glucose consumption increased and cerebral oxygen consumption decreased significantly. During seizures, cerebral metabolic rate for oxygen increased. No important changes in ammonia metabolism were noted. It was concluded that it is feasible to apply these methods concurrently in patients with cerebrovascular disease before and after therapeutic trials.

Anaerobic metabolism in the human fetus: II. The twin delivery

Abstract 1.1. Determination of lactate and pyruvate in umbilical vein blood, with enzymatic methods, was done in 244 normal deliveries. In addition umbilical artery blood was analyzed in 21 and maternal arterial blood in 14 cases. 2.2. At birth the concentrations of lactate and pyruvate and the lactate/pyruvate ratio are elevated, as compared to resting values in pregnant subjects at term. 3.3. The increase in lactate, pyruvate and L/P ratio in cord blood is probably of maternal origin. Indeed, (a) there exists a good relationship between the concentrations of lactate and pyruvate in the maternal arterial blood and in the umbilical vein blood; (b) there are no significant umbilical arteriovenous differences either in lactate or pyruvate content or in excess lactate. The value for excess lactate averages +0.16 ± 0.57 mg. per 100 ml. (standard deviation=2.6). Hence the fetus does not produce normally significant quantities of lactate and pyruvate. Furthermore, the fact that there is no considerable fetal production of excess lactate indicates that the fetus does not have to resort to any great amount of anaerobic tissue metabolism; and (c) the muscular activity incident to labor is the principal factor which determines the amount of the increase of lactate and pyruvate in umbilical vein blood. Maximal values are reached in primiparas, followed by a progressive fall up to para iv, after which no further significant decrease is exhibited. 4.4. During normal delivery the oxygen supply to the fetal tissues may, as a general rule, be considered adequate.

Anaerobic metabolism in the human fetus: I. The normal delivery

1.1. Determination of lactate and pyruvate in umbilical vein blood, with enzymatic methods, was done in 244 normal deliveries. In addition umbilical artery blood was analyzed in 21 and maternal arterial blood in 14 cases.2.2. At birth the concentrations of lactate and pyruvate and the lactate/pyruvate ratio are elevated, as compared to resting values in pregnant subjects at term.3.3. The increase in lactate, pyruvate and L/P ratio in cord blood is probably of maternal origin. Indeed, (a) there exists a good relationship between the concentrations of lactate and pyruvate in the maternal arterial blood and in the umbilical vein blood; (b) there are no significant umbilical arteriovenous differences either in lactate or pyruvate content or in excess lactate. The value for excess lactate averages +0.16 ± 0.57 mg. per 100 ml. (standard deviation = 2.6). Hence the fetus does not produce normally significant quantities of lactate and pyruvate. Furthermore, the fact that there is no considerable fetal production of excess lactate indicates that the fetus does not have to resort to any great amount of anaerobic tissue metabolism; and (c) the muscular activity incident to labor is the principal factor which determines the amount of the increase of lactate and pyruvate in umbilical vein blood. Maximal values are reached in primiparas, followed by a progressive fall up to para iv, after which no further significant decrease is exhibited.4.4. During normal delivery the oxygen supply to the fetal tissues may, as a general rule, be considered adequate.

“Partial anaerobiosis” in the human fetus: Oxygen content and arteriovenous lactate differences in umbilical cord blood

“Partial anaerobiosis” in the human fetus: Oxygen content and arteriovenous lactate differences in umbilical cord blood

MYOCARDIAL METABOLISM IN STARVED AND HYPOPROTEINEMIC DOGS

The myocardial metabolism in dogs during starvation and during hypoproteinemia produced by plasmapheresis have been investigated, using the coronary sinus catheterization. In addition, the effects of glucose, mixed amino acid preparation, and cardiac glycosides on them have been observed. Following results were obtained. 1) After about a week of fast, the myocardial extraction of carbohydrates was markedly decreased (in some cases, the coronary arteriovenous differences of glucose, lactate, and pyruvate were negative) and that of fats was increased, accompanied by depression of the myocardial respiratory quotient. The myocardial extractions of oxygen and amino acids were scarcely altered. Cardiac function was generally depressed. During starvation, fat comes to main fuel in the heart instead of carbohydrate as in the other organs. 2) When dogs in the above condition were given 50 per cent glucose, the myocardial extraction of carbohydrates was markedly increased with the abnormally marked elevation of the arterial levels, that of fats and amino acids decreased, that of oxygen increased, and the myocardial respiratory quotient elevated. Following the administration of mixed amino acid peparation, the myocardial metabolism showed a tendency to return to the normal state, but the effect of it was inferior to that of glucose. Following the administration of digitoxin, there was no obvious change in cardiac metabolism and function. Following the administration of strophanthin, the myocardial metabolism was altered little, but the cardiac function was somewhat recovered. 3) In dogs with hypoproteinemia, changes in cardiac metabolism and function showed the same tendencies as in starved dogs, except for decrease of oxygen extraction. During hypoproteinemia, the heart derives its energy from fat mainly as during starvation. 4) When dogs in the above condition were given 50 per cent glucose, the myocardial metabolism showed a tendency to return to the normal state. After mixed amino acid preparation, the myocardial extractions of oxygen and carbohydrates were considerably increased, that of fats decreased, the myocardial respiratory quotient elevated, and thus the myocardial metabolism recovered remarkably. Concerning cardiac glycosides, the same results were obtained as in starved dogs.

MYOCARDIAL LACTATE METABOLISM IN HEALTH AND DISEASE, STUDIES BY CORONARY SINUS CATHETERIZATION

The coronary sinus catheterization was carried out on ninetyeight human subjects, including twenty-two normal subjects, fourty patients with cardiac failure, thirteen patients with coronary sclerosis, six cases of hypertension, six cases of anemia, ten patients with hyperthyroidism, and one patient with beri-beri. In these subjects, the myocardial lactate metabolism was investigated in the recumbent rest, in the exercise test, and in the 10% oxygen hypoxia test, as well as during the intravenous administration of Lanatoside C or Vitamin B1. The results thus obtained were as follows. 1. In the healthy individuals with the mean arterial lactate concentration of 7.79±1.30mg per dl the coronary venous lactate concentration averaged 3.80±0.60mg per dl, the coronary arterio-venous lactate difference 3.99±0.79mg per dl, and the myocardial lactate O2 extraction ratio 30.5±6.4 per cent. The relationship of the coronary arterio-venous lactate difference (ΔL) plotted against arterial lactate concentration (La) follows the next formula, and the rising arterial lactate concentration upon the exercise test resulted in increased coronary arterio-venous lactate difference according to the same formula. La=0.116 ΔL2+0.608 ΔL+3.15 Consequently, in this report, the problems of the myocardial lactate extraction were discussed on the basis of the myocardial lactate extraction coefficient ratio (ΔL/ΔLn):ΔLn is the normal value of the coronary arterio-venous lactate difference, corresponding to a particular arterial lactate level in the formula. In the resting state as well as upon the exercise test, the increases in the arterial lactate concentration were accompanied with a rise in the myocardial lactate O2 extraction ratio, and at the arterial lactate concentration of 30mg per dl the ratio reached approximately to 90 per cent. 2. In the moderate and severe cardiac failure the coronary venous lactate concentration was significantly elevated, and in the severe cardiac failure both the coronary arterio-venous lactate difference and the myocardial lactate O2 extraction ratio were significantly reduced. In cardiac failure as well as in coronary sclerosis or hypertension, the myocardial lactate extraction was significantly lowered, resulting in lowered myocardial lactate O2 extraction ratio as compared with that of the normal at a comparable arterial level. It was noteworthy that in cardiac failure these decreases were in parallel with the grade of its severity. In addition, the decreases in these heart diseases became more evident by the exercise test and the hypoxia test. The data described above suggests that the myocardial lactate metabolic abnormality is not due to the secondary effect of the cardiac failure but precedes it. 3. In the cases of thyrotoxicosis and anemia the coronary venous lactate concentration was significantly elevated, and both the coronary arterio-venous lactate difference and the myocardial lactate extraction were significantly lowered. One patient with beri-beri showed also a remarkable reduction in the myocardial lactate extraction. Additionally, in thyrotoxicosis the myocardial lactate O2 extraction ratio was significantly lowered, and in severe anemia and in beri-beri the ratios were lowered as compared with that of the normal at the same arterial level. Moreovere, these abnormalities became conspicuous by the exercise test. 4. After the administration of Lanatoside C to the cases of cardiac failure the myocardial lactate extraction was significantly improved in contrast with the control patients. 5. The myocardial lactate usage was determined in eight healthy individuals and nineteen patients with heart diseases. The normal value was distributed widely between 0.47 and 3.75mg per dl per 100 grams per minute (Mean value:1.88±0.88).

Coronary blood flow and myocardial metabolism during hypoxia in adrenalectomized-sympathectomized dogs.

The coronary blood flow and carbohydrate metabolism of the heart during hypoxia were studied in two groups of dogs: a) intact animals, and b) those subjected to adrenalectomy and thoracic sympathectomy. The coronary sinus was catheterized via the external jugular vein. The coronary blood flow was measured by the nitrous oxide desaturation technique, and the coronary arteriovenous differences of oxygen, glucose, lactate and pyruvate were determined. A similar increase in coronary blood flow and a comparable change in myocardial carbohydrate metabolism were found during hypoxia in both groups of animals. In the adrenalectomized and partially sympathectomized dogs these changes took place without the increase in heart rate or blood pressure found in the intact animals. It is concluded that the increase in coronary blood flow during hypoxia is not necessarily mediated by either the cardiac sympathetic nerves or the adrenal glands. Local metabolic factors are the primary determinants of coronary blood flow.

Effect of hypotension due to spinal anesthesia on coronary blood flow and myocardial metabolism in man.

The induction of spinal anesthesia resulted in hypotension and decreased coronary blood flow and myocardial oxygen consumption. At the same time the myocardial extraction coefficient of oxygen was not increased, indicating myocardial oxygenation to be adequate for the lower work load. This does not imply that local ischemia might not occur in the presence of coronary artery sclerosis. The coronary arteriovenous differences of glucose, lactate and pyruvate were not changed during the period of hypotension.

Effects of hypoxia on the myocardial metabolism of intact dogs.

Coronary blood flow and myocardial oxygen and carbohydrate metabolism were studied in normal intact dogs subjected to different Degreess of hypoxia. Total left ventricular oxygen consumption was maintained during administration of 10 per cent and 5 per cent oxygen owing to increase in coronary flow and myocardial oxygen extraction. Ten per cent oxygen administration had little effect on carbohydrate uptake by the heart. Five per cent oxygen resulted in decreased coefficients of extraction for glucose, lactate and pyruvate, but total utilization was maintained. Complete anoxia resulted in negative arteriovenous differences for lactate and markedly decreased or negative values for pyruvate.