Antidysrhythmic and Dose-Related Hemodynamic Effects of Manganese in Perfused Isolated Rabbit Hearts

Abstract

Hemodynamic and antidysrhythmic studies were performed to determine the effects of manganese (Mn) on inotropy and chronotropy in normally perfused isolated rabbit hearts (IRHs), and the efficacy of Mn in suppressing and terminating ventricular dysrhythmias (VDs) in regionally ischemic IRHs. Four groups of eight hearts were perfused with Krebs-Ringer bicarbonate solution (KRB) during the control period, followed by 10 min of perfusion with either KRB, as control, or KRB containing 1.0 mM (A), 0.1 mM (B), or 0.01 mM (C) MnCl2. All hearts were then again perfused, for 10 min, with KRB alone (washout). A caused marked depression of heart rate (HR), peak left ventricular (LV) systolic pressure (PSP) and peak LV dP/dt, B resulted in significant depression of HR alone, and C resulted in significant increases in PSP and dP/dt, with a slight fall in HR. Negative effects of Mn were rapidly reversed during washout. Sustained (greater than 2 min) VDs were induced in five of six by sequential bolus injections of isoproterenol and procaine, following ligation of the left marginal coronary artery. A second group of identically treated hearts developed identical VDs with the same frequency, but were reverted to sinus rhythm by a 2-mol bolus of 10 mM MnCl2, without induction of AV block. In a third group of hearts, treated as described for the two groups above, but perfused with KRB containing 0.1 mM Mn, only one of six developed a sustained VD. These results encourage further work, in ischemic whole animal models, to determine the antidysrhythmic efficacy of manganese.