title: The effects of verapamil on mitochondrial dysfunction associated with coronary reperfusion.
abstract: In order to clarify the protective mechanism of verapamil, the following experiment was performed. Twenty-four anesthetized dogs were divided into 3 groups of 8 animals each. In the first, the left anterior descending coronary artery (LAD) was occluded for 15 min; in the second, 5-min reperfusion was done following a 15-min occlusion; in the third, prior to 5-min reperfusion, verapamil (0.4 mg/kg) was infused for 5 min. In each group, heart mitochondria were prepared from the normal and occluded or reperfused areas and their functions were estimated polarographically. The contents of calcium, phospholipids and fatty acids in the mitochondria were also measured by atomic absorption spectrophotometry, Allen's method and gas chromatography, respectively. Although occlusion induced mitochondrial dysfunction, the dysfunction was exacerbated by reperfusion. Occlusion alone did not alter the contents of calcium, phospholipids and fatty acids in mitochondria, while occlusion and subsequent reperfusion increased calcium and fatty acids and decreased phospholipids in mitochondria. Verapamil prevented these reperfusion responses. These results suggest that reperfusion injury of mitochondria is based on the degradation of mitochondrial phospholipids, which is caused by an activation of phospholipase, being triggered by a calcium increase. Verapamil, a calcium antagonist, might protect against reperfusion injury by inhibiting the activation of phospholipase.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation; D004285:Dogs; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010101:Oxygen Consumption; D010477:Perfusion; D010740:Phospholipases / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D005227:Fatty Acids; D014700:Verapamil; D010740:Phospholipases; D002118:Calcium