Manganese and the heart: Acute cardiodepression and myocardial accumulation of manganese

The aim of study was to assess acute effects oi the divalent manganese ion (Mn2+) in an intact bur isolated heart preparation. Rat hearts were perfused in the Langendorff mode at constant flow rate. Left ventricular (LV) developed pressure (LVDP), LV pressure first derivatives (LVdp/dt max and min), heart rate (HR) and aortic pressure (AoP) were recorded. Ventricular contents of high energy phosphate compounds (HEP) and Mn metal were measured at the end of experiment. Infusion of MnCl2 for 5 min with perfusate concentrations 1-3000 mu M induced an immediate depression of contractile function at and above 33 mu M and negative chronotropy at and above 300 mu M. These EC(50) values were found (mu M): LVDP 250: LVdp/dt max 160. LVdp/dp min 120, HR 1000; and increase in AoP 80. Recovery of function during a 14 min washout period was rapid and extensive. except for Mn2+ 300 mu M. Somewhat unexpected, Mn2+ 30-1000 mu M raised coronary vascular resistance up to about twice the control level, whereas the vasoconstrictory response was overcome at 3000 mu M. Mn2+ 3000 mu M reduced tissue HEP. Ventricular Mn content rose stepwise for perfusate Mn2+ above 1 mu M UP to about 55 times the control level for perfusate Mn2+ 3000 mu M, it is concluded that: acute effects of Mn2+ like depression of contractility and rate is rapidly reversible: and rat hearts accumulate and buffer large amounts of Mn2+ without affecting cardiac function or energy metabolism in the acute stage.