Myocardial protection by micromolar manganese in the calcium paradox and additive effects of verapamil.

The aims of the present study were to establish if micromolar manganese (50 mumol) may substitute for calcium during calcium-free perfusion and also to assess if manganese substitution for calcium may ensure tissue protection by verapamil (1.0 mg/l). Two injury levels (minimal and total calcium paradox) caused by different volumes (5 ml and 45 ml) of calcium-free perfusion (5 min) prior to calcium repletion (15 min) were examined in a normothermic isolated rat heart model. The presence of manganese during calcium-free only (5 min) or the presence of manganese prior to (5 min), during (5 min), and following (5 min) calcium-free perfusion conferred considerable protection as assessed by enzymatic, physiological and metabolic parameters in both the total and minimal calcium paradox models. The presence of verapamil prior to (5 min), during (5 min) and following (5 min) calcium-free perfusion combined with the presence of manganese conferred a further protection, particularly in the total paradox. It is concluded from the study that 50 mumol of manganese, although effective in tissue protection, cannot substitute totally for the loss of calcium during calcium-free perfusion and that manganese may substitute for the micromolar calcium needed for tissue protection by verapamil.