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

Adenosine release by the myocardium has been linked to a decrease in myocardial oxygen content and has been implicated in producing the concomitant increase in coronary flow. Epinephrine, norepinephrine, and histamine increase myocardial oxygen consumption and coronary flow. Nitroglycerin on the other hand, increases coronary flow but does not increase oxygen consumption. The purpose of the present study was to determine whether changes in coronary sinus oxygen levels induced by these drugs are closely associated with changes in adenosine release. Isolated guinea pig hearts were perfused with Krebs-Henseleit solution (pH 7.4,37°C) aerated with 95% O25% CO2. Coronary flow, contractile force, coronary sinus oxygen levels, and adenosine and its degradative products in perfusates were measured before and during the infusion of varying doses of epinephrine, norepinephrine, histamine, or nitroglycerin. All four compounds produced significant increases in coronary flow. The catecholamines and histamine had a positive inotropic effect, increased myocardial oxygen consumption, and decreased coronary sinus oxygen levels. The decrease in coronary sinus oxygen was accompanied by increased levels of adenosine in the perfusates. Nitroglycerin, on the other hand, did not change contractile force, increased coronary sinus oxygen levels, and did not increase the rate of adenosine release. Changes in inosine and hypoxanthine, degradative products of adenosine metabolism, paralleled those of adenosine in all experiments. These findings indicate that adenosine release is intimately associated with a reduction of coronary sinus oxygen levels and, further, that adenosine is not a mediator in the vasodilation induced by nitroglycerin.