The effects of dilazep on reperfusion arrhythmias.

The effects of 3,3'-(perhydro-1,4-diazepine-1,4-diyl) (propyl-3,4,5-trimethoxybenzoate (dilazep, Comelian) on reperfusion arrhythmias were investigated. 49 adult mongrel dogs were divided into 2 groups; the control group (n = 38) and the dilazep group (n = 11). 15 min after premedication with physiological saline or dilazep (2 mg/kg), the left anterior descending coronary artery was occluded for 15 min and then reperfused for 5 min. 12 dogs (32%) of the control developed "reperfusion arrhythmias" (arrhythmias cases) but 26 did not (non-arrhythmias cases). None of the 11 dogs pretreated with dilazep developed arrhythmias (dilazep group). Immediately after 5 min of reperfusion, plasma membrane and microsomes were prepared from the normal and reperfused myocardium. In the arrhythmias cases of the control group, an increase in free fatty acids and a decrease in phospholipids of plasma membrane obtained from the reperfused myocardium were observed. The endogenous phospholipase activity in the heart microsomes obtained from reperfused myocardium increased significantly compared with that from the normal myocardium. In the non-arrhythmias cases of the control group and in the dilazep group, there was no significant difference in the contents of free fatty acids and phospholipids in plasma membrane between normal and reperfused area. Phospholipase activity in the microsomes prepared from the reperfused myocardium did not change significantly compared with that in the microsomes from normal area in these groups. These results suggest that the activation of phospholipases associated with coronary reperfusion is closely related to the development of reperfusion arrhythmias.