Effects of in vivo manganese administration on calcium exchange and contractile force of rat ventricular myocardium

Summary

The purpose of this study was to investigate the effect of prolonged (14 days) intragastric administration of Mn²⁺ (0.25 mmol/kg daily) on Ca²⁺ exchange and contractility of rat ventricular myocardium. Left-ventricular pressure and its first derivative (dP/dt) were recorded by means of a balloon catheter inserted via the left atrium into the left ventricle of the rat heart perfused by Langendorff method. Ca²⁺ exchange in the stimulated and rested ventricular myocardium was investigated with the aid of⁴⁵Ca under the conditions of complete equilibration of preparations with a solution containing⁴⁵Ca²⁺. The “cellular”⁴⁵Ca²⁺ content was calculated by subtraction of⁴⁵Ca²⁺ dissolved in the free water of extracellular space from the total tissue⁴⁵Ca²⁺ content. The cellular⁴⁵Ca²⁺ content in the stimulated (60/min) ventricles of control rats (without Mn²⁺) was 0.83 ± 0.09 mmol/kg wet weight (w.w.). Ten minutes of rest resulted in a gain of 0.06 mmol⁴⁵Ca/kg w.w. (not statistically significant). Fourteen days' exposure to Mn²⁺ resulted in an increase of the mean⁴⁵Ca content to 1.61 ± 0.09 mmol/kg w.w. in the stimulated preparations and to 1.35 ± 0.06 mmol/kg w.w. in the rested ones (p < 0.001). Thus, the control rest preparations did not change their Ca²⁺ content, while in the rats treated with Mn²⁺ the rest resulted in an increase at exchangeable Ca by 52 %. The maximal ventricular developed pressure (P_max) after 14 days of Mn²⁺ administration was increased by 35 % and dP/dt_max was 228 % of the value in the control group. The mean time from the maximal value of the first derivative to P_max (t-dP/dt_max) was reduced by one-half and mean time to peak developed pressure (TPT) was shortened to one-third of these in the control group. These results, although far from conclusive, do suggest that the long-lasting exposition to Mn²⁺ resulted in increased myocardial contractility caused, most probably, by the inhibition of Ca²⁺ efflux from the cell. Perhaps this is a compensation for the inhibitory effect of Mn²⁺ on the slow calcium channels.