Although the protective effects of the
calcium antagonists on ischemic and reperfused myocardium have been investigated, there have been only a few reports regarding their efficacy in relation to the degree of ischemic myocardium. This study was undertaken to investigate the efficacy of
diltiazem, a
calcium antagonist, in relation to the degree of ischemic myocardial injury in an isolated working rat heart. Three different models of ischemic injury were designed; Group A: 30 min global
ischemia with a single dose infusion of St. Thomas'
cardioplegic solution (STS), Group B: 60 min global
ischemia with multidose infusion (every 30 min) of STS and Group C: 60 min global
ischemia with multidose infusion (every 15 min) of STS. These groups received only STS, while Groups A-D, B-D and C-D (the treated groups) received the same
solution with
diltiazem (0.5 mumol/l). The recovery of post-ischemic cardiac function and the CPK leakage during reperfusion were evaluated, and the two groups were compared. For 30 min global
ischemia, the addition of
diltiazem to STS significantly improved the percentage recovery ratio of aortic flow (63.2 +/- 8.6% vs 79.9 +/- 5.9%, control vs.
diltiazem, p < 0.01) and reduced CPK leakage during reperfusion (87.5 +/- 35.8 IU/20 min/g dry wt vs. 41.7 +/- 14.5 IU/20 min/g dry wt, control vs.
diltiazem, p < 0.05). However, no differences in the post-ischemic functional recovery and CPK leakage were noted between the groups for 60 min global
ischemia. In conclusion, for myocardial preservation, the addition of diltizaem to St. Thomas'
cardioplegic solution was less effective for the 60 min global
ischemia. Regarding severe
myocardial ischemia, it was suggested that, inhibitation or suppression of
calcium channel by diltizaem might insufficient to obtain additional protection of the St. Thomas'
cardioplegic solution. Therefore, it would be necessary to control
calcium entry through another pathway during
ischemia and reperfusion.