Effects of catecholamines, histamine, and nitroglycerin on flow, oxygen utilization, and adenosine production in the perfused guinea pig heart.

Abstract

Whether changes in coronary sinus O2 levels induced by these drugs are closely associated with changes in adenosine release was examined. Isolated guinea pig hearts were perfused with Krebs-Henseleit solution (pH 7.4, 37.degree. C) aerated with 95% O2-5% CO2. Coronary flow, contractile force, coronary sinus O2 levels and adenosine and its degradative products in perfusates were measured before and during infusion of varying doses of epinephrine, norepinephrine, histamine or nitroglycerin. All 4 compounds produced significant increases in coronary flow. The catecholamines and histamine had a positive inotropic effect, increased myocardial O2 consumption and decreased coronary sinus O2 levels. The decrease in coronary sinus O2 was accompanied by increased levels of adenosine in the perfusates. Nitroglycerin did not change contractile force, increased coronary sinus O2 levels and did not increase rate of adenosine release. Changes in inosine and hypoxanthine, degradative products of adenosine metabolism, paralleled those of adenosine in all experiments. Adenosine release apparently is intimately associated with a reduction of coronary sinus O2 levels and is probably not a mediator in the vasodilatation induced by nitroglycerin.