Examination of diltiazem for preservation of myocardial function after brief regional ischemia

Diltiazem (750 micrograms/kg plus 600 micrograms/kg/h X 1 h, i.v.) and vehicle were examined in open-chest anesthetized dogs subjected to 15 min of occlusion of the left circumflex coronary artery (LCCA). Regional segment lengths in myocardium supplied by the LCCA and by the left anterior descending coronary (LAD) were measured with piezoelectric crystals implanted in the subendocardium. Diltiazem decreased heart rate and mean arterial pressure, and increased coronary blood flow, determined with an electromagnetic flowmeter. Vehicle had no significant effects. Occlusion of the LCCA increased end diastolic segment length (EDL), and produced akinesis or paradoxical systolic lengthening: diltiazem -2.5 +/- 2.7% and vehicle 0.0 +/- 1.2% segmental shortening (SS). EDL and SS in the LAD zone showed small increases. After 15 min, the LCCA was reperfused and recovery of SS was followed for 3 h. Significantly greater recovery of SS was observed with diltiazem compared to vehicle throughout reperfusion: at 5 min, diltiazem 105 +/- 22% and vehicle 43 +/- 7% and at 180 min, diltiazem 73 +/- 0% and vehicle 33 +/- 8% of baseline SS. The LCCA and LAD zones both responded to isoproterenol 0.3 microgram/kg given 2.5 h after reperfusion. During the isoproterenol challenge SS for LCCA in the diltiazem group (122 +/- 21%) was not different than that of vehicle (99 +/- 15% of baseline). Calcium entry blockade with diltiazem resulted in improved myocardial function during reperfusion. The stunned myocardium showed significant stimulation of shortening by isoproterenol in both groups.