Prolonged depression of segmental systolic thickening after brief coronary artery occlusion may result principally from events during reperfusion rather than during the ischemic interval. Thus, cellular
calcium overload at reperfusion may be a mediator of contractile dysfunction after brief
ischemia, and reduction of
calcium entry by
diltiazem, a
calcium channel antagonist, may enhance recovery of systolic thickening after brief periods of
ischemia. Thirteen awake unsedated dogs instrumented with hemodynamic
catheters, left anterior descending coronary artery occluders and five to six pairs of intramyocardial sonomicrometers underwent two 15 min coronary artery occlusions with 24 h reperfusion. The order of infusion of
diltiazem (15 micrograms/kg per min) or
saline solution was alternated. Systolic thickening, hemodynamic variables and regional myocardial blood flow were measured serially over 24 h. Despite equally severe ischemic dysfunction during
coronary occlusion,
diltiazem-treated segments with systolic thinning during
ischemia recovered control segmental thickening significantly earlier than
saline solution-treated segments (at 30 versus 180 min of reperfusion). Blood pressure was mildly decreased during
diltiazem treatment; therefore, a second group of 10 dogs underwent a similar occlusion and reflow period during infusion of
nitroprusside to lower mean arterial pressure equivalently. Decreases in blood pressure in this group resulted in some improvement in segmental systolic function; however, this did not reach statistical significance at any time. Regional myocardial blood flows were similar in the
saline solution- and
diltiazem-treated groups during
ischemia and reflow. Thus, it is concluded that 1)
diltiazem infusion significantly enhanced recovery of segmental systolic thickening after 15 min of
ischemia and 24 h of reperfusion; 2) the enhancement in segmental systolic function could not entirely be attributed to decreased mean arterial pressure; 3) improvement in postischemic segmental ventricular function was seen only in those segments with systolic thinning during
ischemia; thus, segments with the most severe ischemic dysfunction benefited most; and 4) there were no important differences in regional myocardial blood flow during
ischemia and reperfusion between saline- and
diltiazem-treated animals.