Children with left-to-right shunt, with and without congestive heart failure, were found to have impaired glucose tolerance tests (GTT). In cyanotic children normal levels of glucose were found in association with abnormally high levels of insulin following oral GTT. Several possible mechanisms are proposed to explain the different glucose tolerance alterations: (1) Suppression of insulin release appeared to partially explain the low levels of insulin in congestive heart failure. This suppression may be related to the high levels of circulating norepinephrine found in these patients. (2) Excessive clearance of insulin by the lung may also be responsible for the reduced arterial insulin levels in patients with left-to-right shunt, and underclearance of insulin for the abnormally higher arterial insulin levels in patients with right-to-left shunts in whom a significant amount of venous blood has bypassed the lung. (3) Hypoxia of the pancreas and the liver in cyanotic patients and those with congestive heart failure may explain the reduction of insulin levels in the hepatic vein following i.v. glucose tolerance tests. An excess production of a glucagonlike gastrointestinal factor in cyanotic children may partially explain the abnormally high levels of insulin following oral GTT.
I t has been reported that ouabain exerts in vitro metabolic effects characterized by an inhibition of spontaneous (1) and epinephrinestimulated glycogenolysis (2,3) and lipolysis (2,4,5). All these in vitro studies were performed with high concentrations of ouabain M ) . The purpose of the present study was to determine if ouabain exerted metabolic effects in intact animals in a dosage much lower than that used in vitro, and if a similar interaction with the metabolic effeot of epinephrine occurred. Assuming that the total dose of ouabain administered to the animals (1 &g/kg per min for 60 min) accumulated in a volume of water approximating extracellular water, the final concentration would be about lo-' M . This dose is at least 100 times less than that used in vitro.Methods. Experiments were performed on 14 pedigreed male beagles less than 1 year old and fasted for 18 hours before the experiment. The animals were anesthetized with 35 mg/kg of Na pentobarbital, intravenously administered, and intubatd with a cuffed endotracheal tube. Mechanical ventila&ion with 100% 02 was administered at constant rate and volume so as to maintain normal acid-base equilibrium and 0 2 saturation in arterial blood throughout the experiment. Muscle relaxation was maintained with succinylcholine chloride. Each animal served as his own control and was studied twice at no less than a week's interval according to a protocol previously described ( 6 ) .Two series of experiments were performed. I n the first series of experiments on 6 dogs, following the control period, ouabain (1.0 pg in 0.1 ml of saline/kg per min) was administered i.v. for 60 min. Observations were M to *This work was supported, in par,t, by Army Contract DADA-17-67-C-7126 and N.I.H. G,rant GM-09069-05.continued for 60 min following the end of ouabain administration. I n the control experiment, the same volume of saline as of ouabain was administered. In the second series of experiments on 8 dogs, the effect of ouabain on the metabolic activity of epinephrine was studied. After the control period, ouabain (1.0 Fg,kg per min) was administered to the mi-ma1 for 60 min in the same volume as given in the first series. During the last 30 min of this infusion, epinephrine (0.8 pg in 0.1 ml of saline/kg per min) was administered intravenously. Observations were continued for 60 min following the end of drug infusion. In the control experiment performed on the same animal, a volume of isotonic saline equal to that of ouabain was given while the same dose of epinephrine was administered. As in the first series, the sequence of ouabain-saline administration was reversed from one animal to the next. Specific methods of measurements have been described in previous publications (6). The data was analyzed statistically according to the Student t test. The significance of differences between paired measurements was calculated by the method of difference between correlated pairs. The p was evaluated within 5% limit of confidence.Results. Ouabain administration. Mean blood pressure i...
Effects of epinephrine (10(-5) M) on mechanical performance, glycolysis, glycogenolysis, lipolysis, and metabolism of adenine nucleotides were studied in isolated hypoxic rabbit hearts. The exposure of hearts to hypoxia decreased their mechanical performance and heart rate, but increased their utilization of glucose by 50% and the release of lactate by 139%. Myocardial stores of glycogen and ATP declined by 53 and 84%, respectively, but their breakdown products such as lactate, pyruvate, AMP, and inosine accumulated in these hearts. Myocardial content of free fatty acids decreased, and the amount of glycerol increased in hypoxic hearts. Epinephrine stimulated mechanical performance and heart rate of hypoxic hearts, but decreased myocardial glycogen and ATP even more by 62 and 33%, respectively. Though glucose utilization remained unchanged, the release of lactate increased by 66% from hypoxic hearts treated with epinephrine. However, epinephrine failed to stimulate myocardial lipolysis in hypoxic hearts. These metabolic changes due to epinephrine would lead to accelerated depletion of energetic reserves in hypoxic heart and its earlier deterioration.
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