ve To investigate the effects of different doses of
diltiazem alone or combination with
isoflurane on stunned isolated rat
heart. Methods Adult male Wistar rats weighing 325-350g were anesthetized with intraabdominal pentobarbital sodium 60mg·kg-1. Heparin 200IU was injected into femoral vein. Chest was then opened and heart was removed and connected to Langendorff preparation. The isolated rat heart was perfused at 100cm H2O with Krebs-Hensleit buffer(KHB) balanced with 95%O2 and 5%CO2 at 37℃ and electrically paced at 300 bpm. Global myocardial ischemia was produced by suspension of perfusion. The isolated rat heart underwent 20 min ischemia followed by 30min reperfusion. 40 rat hearts were randomly allocated to one of 5 groups of eight each, group Ⅰ received no treatment and served as control; group Ⅱ: the isolated heart was perfused with 0.1/μmol·L-1 diltiazem for 10 min before the onset of ischemia; group Ⅲ: with 0.5μmol·L-1 diltiazem; group Ⅳ: with 0. 1μmol·L-1 diltiazem + 1.5MAC
isoflurane; group Ⅴ: with 0.5μmol·L-1 diltiazem + 1.5MAC isoflurane. Left ventricle developed
pressure(DP) was measured from a fluid-filled Latex balloon placed in left ventricle. The volume of the fluid in the balloon was regulated to maintain the left ventricle end-diastolic pressure at 5-8 mm Hg. Peak systolic pressure(PSP), end-diastolic pressure(EDP) and developed pressure(DP) were measured after the isolated heart was stabilized for 10min (baseline value) and 5, 10, 15, 20, 25, 30min after reperfusion. Maximum intraventricular pressure was measured during ischemia when the isolated heart was not paced and at a stand still. Results There was no significant difference in DP, EDP, + dp/dtmax and - dp/dtmin after the isolated hearts were stabilized for 10min, before ischemia among the five groups. Perfusion with 0.1μmol·L-1 diltiazem did not affect DP significantly but 0.5μmol·L-1 diltiazem significantly decreased DP (P < 0.05) and further decrease in DP was produced by 0.5μmol·L-1 diltiazem combined with isoflurane. DP recovered significantly better after 30min of reperfusion in group Ⅲ, Ⅳ and Ⅴ(84 % , 92 % and 95% of the baseline value) as compared with that in group Ⅰand Ⅱ(52% and 66% of the basline value) .EDP increased in all groups after ischemia but the increse was significantly less in group Ⅲ, Ⅳand Ⅴ than that in group Ⅰ and Ⅱ. Better recovery of + dp/dtmax and - dp/dtmin was also seen in group Ⅲ, Ⅳand Ⅴ than that in group Ⅰ and Ⅱ. Conclusions Diltiazem protects myocardium against stunning in a dose-dependent manner. Isoflurane can inhance the protective effect of low dose diltiazem.