Nitric oxide does not modulate myocardial contractility acutely in in situ canine hearts

Abstract

The study was designed to assess the influence of nitric oxide (NO) on myocardial contractility in vivo. The left anterior descending coronary artery (LAD) of 28 anesthetized, open-chest dogs was perfused with arterial blood via an extracorporeal circuit. In the LAD bed, segmental shortening (SS), an index of local myocardial contractility, was measured with ultrasonic crystals. Coronary blood flow (CBF) was measured by Doppler flow transducer and used to calculate myocardial oxygen consumption (MVO2). Studies were performed with coronary perfusion pressure (CPP) constant (n = 23) or with CBF constant (n = 5). Measurements were obtained 1) during intracoronary infusions of the NO donors sodium nitroprusside (SNP, 80 ng/min) and nitroglycerin (NTG, 40 micrograms/min) and of a stimulator of endogenous NO release, acetylcholine (ACh, 20 micrograms/min), and 2) after inhibition of basal NO synthase activity with either NG-nitro-L-arginine methyl ester (L-NAME, 300 micrograms/min ic for 15 min) or NG-monomethyl-L-arginine (L-NMMA 2mg/min ic for 15 min). Decreases in SS (-38%) and MVO2 (-42%) during intracoronary isoflurane infusion verified responsiveness of preparation to negative inotropic agents. With CPP constant, SNP, NTG, and ACh caused increases in CBF (177, 28, and 280%, respectively) with no changes in SS or MVO2. Neither L-NAME nor L-NMMA affected SS, MVO2, or CBF. With CBF constant, the SNP- and ACh-induced decreases in CPP were accompanied by no changes in SS. In conclusion, NO had no direct influence on myocardial contractility or oxygen demand under baseline conditions, or when its local concentration was increased acutely with SNP, NTG, or ACh. An augmented SS secondary to increased CBF per se, i.e., Gregg's phenomenon, did not obscure potential negative inotropic effects of SNP and ACh with CPP constant.

Myocardial tissue oxygen during coronary artery constriction and hypotension in dogs

“…These results show that during SNP‐induced hypotension, LAD artery flow increased, which is consistent with reports that SNP produces coronary vasodilation (1–3). Myocardial oxygen tension decreased and coronary sinus PO 2 increased.…”

“…Sodium nitroprusside (SNP), a nitric oxide donor, is a coronary vasodilator that produces little or no change in myocardial contractility or myocardial oxygen consumption (1–4). Little is known of SNP of the effect on myocardial tissue oxygen pressure (PmO 2 ).…”

Activation of Distinct cAMP-Dependent and cGMP-Dependent Pathways by Nitric Oxide in Cardiac Myocytes

“…1 These effects of NO have been ascribed to the activation of soluble guanylyl cyclase (GC), leading to the production of cGMP and activation of cGMP-dependent protein kinase (PKG). 1,2 Furthermore, NO and NO donors have been shown to elicit a wide range of effects on myocardial contractility, [3][4][5][6][7][8][9] but the specific nature of the subcellular mechanisms underlying the diverse effects in heart is largely unknown.…”

Inhibition of nitric oxide synthesis improves left ventricular contractility in neonatal pigs late after cardiopulmonary bypass

“…Given that in unperturbed hearts5 25 26 and at physiological concentrations,27 NO inhibition has little effect on cardiac function, it seems likely that in our model—as in other pathophysiological models—there is increased intracardiac or systemic NO production. However, we did not elucidate whether there was an increase in NO production, a change in NOS activity, or isoform expression.…”