Metabolic effects of low and high doses of insulin during beta-receptor blockade in dogs.
Metabolic effects of low and high doses of insulin during beta-receptor blockade were studied in eight dogs. Beta-receptor blockade was induced by 0.5 mg/kg propranolol which caused depression of heart performance. This was accompanied by a significant reduction in myocardial blood-flow and oxygen consumption. There was also a significant reduction in arterial concentrations and myocardial uptake of free fatty acids, while arterial concentrations and myocardial uptake of glucose and lactate were not significantly changed. Fifteen minutes after beta receptor blockade, an intravenous (i.v.) bolus injection of 0.5 IU/kg, of insulin, free of glucagon and calcium, was given followed by a continuous infusion of 0.5 IU/kg/h. Glucose and potassium were given to maintain constant levels of these factors. After 30 min another bolus dose of 300 IU insulin was injected. Thirty minutes after a low dose of insulin, a significant increase in heart performance was recorded at unaltered myocardial oxygen consumption. Arterial concentrations of free fatty acids were significantly reduced while levels of glucose and lactate were unchanged. Myocardial uptake of glucose increased significantly while uptake of lactate and free fatty acids was unchanged. After a high dose of insulin there was a considerable improvement in heart performance. Myocardial blood-flow and oxygen consumption were not changed, nor were there alterations in arterial concentrations and myocardial uptake of glucose, lactate and free fatty acids. It is concluded that, during beta-receptor blockade high doses of insulin improve the mechanical performance of the heart through mechanisms that are independent of insulin's effects on substrate metabolism.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D005230:Fatty Acids, Nonesterified; D006454:Hemoglobins; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D005947:Glucose; D010100:Oxygen