The left anterior descending coronary arteries of 30 anesthetized, open-chest dogs were perfused via an extracorporeal circuit. Coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and segmental shortening (SS) were measured. Studies were performed with coronary perfusion pressure (CPP) or CBF constant. With CPP constant, effects of intracoronary (IC) infusions of dobutamine (2.5, 5.0, or 10.0 [micro sign]g/min) were evaluated alone (control) and after inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine methyl ester (L-NAME). With CBF constant, a NO donor (sodium nitroprusside [SNP] 80 [micro sign]g/min IC) or nitroglycerin [NTG] 40 [micro sign]g/min IC) or a releaser of endogenous NO (acetylcholine [ACh]; 20 [micro sign]g/min IC) was infused along with dobutamine. Increases in CBF during dobutamine and isoproterenol were compared before and after blockade of beta1-adrenergic receptors with atenolol. Dobutamine caused proportional, dose-dependent increases in CBF, MVO2, and SS, which were not altered by L-NAME. Administration of the NO donors or ACh during dobutamine markedly decreased CPP, but only ACh also reduced SS and MVO2. These latter effects persisted after L-NAME. Atenolol blunted increases in CBF by dobutamine more than those by isoproterenol. We conclude that endogenous NO did not modulate the coronary vasodilation or the increases in myocardial contractility and MVO2 during dobutamine. In addition, neither SNP nor NTG altered myocardial contractility or MVO2 in dobutamine-stimulated myocardium, whereas ACh had a negative inotropic effect in dobutamine-stimulated myocardium that was independent of NO. Implications: Endogenous nitric oxide (NO) did not modulate increases in coronary blood flow, myocardial contractility, or myocardial oxygen consumption during intracoronary infusions of dobutamine. The NO donors sodium nitroprusside and nitroglycerin had no effect on contractility or oxygen consumption in dobutamine-stimulated myocardium. Acetylcholine had negative inotropic effect in dobutamine-stimulated myocardium that was independent of NO.
(Anesth Analg 1998;87:994-1001)