The intracellular
calcium level is increased during
ischemia and early reperfusion. The aim of this study was to study the role of the
calcium influx in the development of myocardial ischemic and
reperfusion injury during the early and late phases of
ischemia and during early reperfusion. An ultrashort-acting
calcium antagonist,
clevidipine, was used as a tool for this investigation.
Pentobarbital-anesthetized pigs were subjected to 45 minutes of LAD occlusion followed by 240 minutes of reperfusion. In the first set of experiments,
clevidipine (0.3 nmol/kg per minute) was infused over 5 minutes into the ischemic myocardium via a
catheter in the LAD, starting at 5, 35, or 44 minutes following the onset of
ischemia (n = 6 in each group). The area at risk and the
infarct size were determined after 240 minutes of reperfusion by staining with
Evans blue dye and triphenyl tetrazolium
chloride (TTC), respectively. In a second set of experiments, two groups of animals (n = 6 in each) were subjected to the same periods of
ischemia and reperfusion; one group received no infusion during
ischemia, whereas the other group received vehicle infusion during a 5-minute period between 5 and 10 minutes of
ischemia. In the first set of experiments, there were no significant differences between the groups with regard to hemodynamic variables. The area at risk expressed as a percentage of the left ventricle was of similar magnitude in all three
clevidipine-treated groups (about 18%). The
infarct size, expressed as a percentage of the area at risk, was significantly smaller in pigs given
clevidipine after 5 minutes (58 +/- 17%; p < 0.01) and after 44 minutes (42 +/- 6%; p < 0.01) of
ischemia than in pigs receiving
clevidipine after 35 minutes of
ischemia (85 +/- 4%). The difference in
infarct size between pigs given
clevidipine after 5 or 44 minutes of
ischemia was not significant. In the second set of experiments, there was a similar area at risk and no significant difference in
infarct size between the noninfusion group and the 5-minute vehicle infusion group, indicating that the LAD infusion per se did not affect
infarct size. The present results demonstrate that blockade of
calcium influx by the short-acting
dihydropyridine calcium antagonist
clevidipine during the early phase of
ischemia and at the time of reperfusion, but not during a late phase of
ischemia, limits
infarct size induced by
ischemia and reperfusion. This indicates that the pathophysiological importance of
calcium influx varies according to the different phases of
myocardial ischemia and reperfusion.