Effects of diltiazem on isoproterenol- or Ca-induced ventricular myocardial cell injuries in isolated perfused rabbit heart: an electron microscopic study.

The ultrastructural changes of isoproterenol- and those of Ca-induced ventricular cell injuries were compared in rabbits and the effect of diltiazem on these injuries was studied by electron microscopy. In comparison with the controls, the isoproterenol-treated (Group A), the Ca-treated (Group B), and the diltiazem-posttreated (Groups E and F) showed severe myocardial cell damage, such as sarcolemmal disruption, mitochondrial swelling, intramitochondrial electron-dense granules, membranous structures along mitochondrial cristae, thickening or close packing of the Z-lines, separation of cell junctions, frayed myofibrils, clumping of chromatin, and intracellular fluid accumulation. These ultrastructural changes were more pronounced in the Ca-treated (Groups B and F) than in the isoproterenol-treated (Groups A and E) animals. In contrast, the diltiazem-pretreated groups (Groups C and D) showed relatively intact myocardial ultrastructure. However, intramitochondrial electron-dense granules could be frequently found, and particularly the diltiazem-pretreated and Ca-treated group (Group D) showed intracellular fluid accumulation. The results of this study could suggest the following: 1) isoproterenol-induced myocardial cell damage is similar to Ca overload, 2) pretreatment with diltiazem could reduce the deleterious effects of isoproterenol-induced myocardial cell damage, but it could not prevent the effects of Ca overload completely, and 3) posttreatment with diltiazem could not provide any beneficial effect either on the isoproterenol-induced or on the Ca-overloaded myocardial cell damage, and 4) the beneficial effects of diltiazem are probably derived from the enhanced buffering function of mitochondria to cytosolic Ca or from selective inhibition of transsarcolemmal Ca influx.