Action of magnesium salts on the toxic effects of calcium overload in isolated and perfused rat heart

The toxic effect of calcium overload and the action of magnesium sulfate (4 mM) and magnesium chloride (4 mM) on heart rate, coronary flow rate, left ventricular systolic pressure, dp/dt max and voltage epicardial electrogram were studied in the isolated and perfused rat heart. Increasing calcium load by increasing [Ca]o from 1 to 6 mM we observed a progressive increase in heart rate coronary flow rate, left ventricular systolic pressure, dp/dt max and a decrease in voltage epicardial electrogram. During the exposure to [Ca]o 8 mM the toxic manifestations of calcium overload developed and we observed a reduction in heart rate, coronary flow rate, left ventricular systolic pressure, dp/dt max and an increase in voltage epicardial electrogram. Magnesium sulfate and magnesium chloride had similar effect: in fact, in both procedures we observed a decrease in heart rate, left ventricular systolic pressure, dp/dt max, voltage epicardial electrogram and an increase in coronary flow rate at [Ca]o 2 mM. When magnesium salts were administered at the same time as the heart was exposed to [Ca]o 8 mM, we observed a reduction in the toxic effect of calcium overload. When magnesium salts were administered after the appearance of the calcium overload, they did not revert the toxic effect of calcium overload but prevented the insurgence of cardiac standstill. Thus, in the isolated perfused rat heart, the toxic manifestations of calcium overload develop at [Ca]o 8 mM and magnesium salts are able to reduce the toxic effects of calcium overload and the appearance of cardiac standstill according to their calcium-antagonism mechanism