Cardiac injury in short duration anoxia and modification by diltiazem, a calcium channel blocking agent

The protective effects of diltiazem were studied in isolated perfused rat hearts after 10, 20 and 30 minutes of anoxia and 10 minutes of reoxygenation. The hearts were treated with diltiazem, 4 mg/liter, during anoxia and reoxygenation. The myocardial tissue was processed for electron microscopy and tissue calcium was measured. Four types of cell injury ranging from normal to severe were observed. The prominent morphologic changes in the nondiltiazem-treated tissue were contraction bands, distortion and calcification of mitochondria and loss of glycogen. In the treated group, a partial reduction of cell injury was noted. The mitochondria were usually well preserved, but contraction bands were present. The tissue calcium decreased after treatment with diltiazem. The observations suggest that diltiazem decreases tissue calcium and protects mitochondria more than other cellular components against calcium overload, and this protection may be responsible for the beneficial action of this drug.