Effect of the alpha 1-blocker bunazosin on reperfusion-induced mitochondrial dysfunction in canine hearts.
The effect of the alpha 1-blocker 4-amino-2-(4-butyryl-hexahydro-1H-1,4-diazepin-1-yl) -6,7-dimethoxy-quinazoline (bunazosin, E-643, Detantol) on reperfusion injury was investigated. 43 anesthetized dogs were divided into two groups: the control group (n = 30) and the bunazosin group (n = 13). 15 min after premedication with physiological saline for the control group, or the alpha 1-blocker bunazosin 0.5 mg/kg for the bunazosin group, the left anterior descending coronary artery was occluded for 15 min and then reperfused for 5 min. Heart mitochondria were prepared from both the normal and reperfused areas. Mitochondria function and their Ca2+ content were measured by polarography and atomic absorption, respectively. Mitochondrial phospholipase activity was measured by high performance liquid chromatography. Nine dogs (30%) of the control group developed reperfusion arrhythmias. None of those pretreated with bunazosin developed arrhythmias. Although mitochondrial dysfunction was observed in the reperfused area in each group, more severe dysfunction was observed in dogs with arrhythmias in the control group. Mitochondrial Ca2+ content in the reperfused area in dogs with arrhythmias increased significantly compared with that in the normal area. Phospholipase activity in the reperfused area in dogs with arrhythmias also increased significantly, but no significant elevation of phospholipase activity was observed in dogs without arrhythmias in both the control and bunazosin groups. These results indicate that reperfusion injury might be closely related to activation of phospholipase linked with alpha 1-adrenergic response.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D010740:Phospholipases / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; C018176:bunazosin; D010740:Phospholipases; D002118:Calcium