Beneficial hemodynamic effects of nicorandil in a canine model of acute congestive heart failure: Comparison with nitroglycerin and cromakalim

Abstract

Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and cromakalim (CRM) were examined in a canine model of acute congestive heart failure (CHF). CHF was produced by injections of saponin into coronary arteries of anesthetized dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt and myocardial segment shortening (SS) markedly decreased, while the left ventricular end-diastolic pressure (LVEDP), the right atrial pressure (RAP) and the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and CRM (n = 8), which were administered i.v. after production of CHF, caused a comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as well as systemic hemodynamic indices to those observed with i.v. NCR despite distinct coronary vasodilation. These results indicate that NCR may exert beneficial hemodynamic effects in an experimental CHF mainly due to lessening both afterload and preload rather than the coronary vasodilating effect.

Positive inotropic effect of nicorandil in adult rats in situ

“…Furthermore, in the canine acute congestive heart failure model, nicorandil may exert beneficial hemodynamic effects mainly due to decrease in both afterload and preload rather than the coronary vasodilator effect [7]. The present result in the adult rat heart, however, revealed that nicorandil increased preload (EDV) without any effects on afterload (Ea and ESP ESV ).…”

“…It was actually reported that at high concentrations nicorandil exerted negative inotropic effects on human left ventricular papillary muscles predominantly by opening the K ATP channels [5]. In acute ischemic and congestive heart failure canine models, nicorandil was considered to improve cardiac contractility due to the reduction of both preload and afterload mediated by K ATP channel opening actions with NO-like actions [6,7]. No positive inotropic effects of nicorandil on the normal heart model, however, have been reported.…”

Nicorandil Prevents Gαq-Induced Progressive Heart Failure and Ventricular Arrhythmias in Transgenic Mice

“…Thus, nicorandil increases coronary blood flow, reduces preload and afterload, and exerts an antianginal action [1], [2]. In addition, beneficial hemodynamic effects of nicorandil have also been demonstrated in acute HF, suggesting a possible effect of this drug in the treatment of HF [3]. In fact, intravenous administration of nicorandil attenuated exercise-induced LV diastolic dysfunction in individuals with hypertrophic cardiomyopathy, probably as a result of its beneficial effect on abnormal coronary microcirculation [4].…”