The Protective Effect Of Shenfu On Myocardial Mitochondria And The Dose-Response Relationship

Objective To investigate the protective effect of Shenfu Injection (SFI) on reperfused rabbit heart and the dose-response relationship. Methods Japanese mature rabbits weighing 2±0.2kg were used. The animals were anaesthetized and heparinized. Chests were opened and hearts were quickly removed to Langend?ff equipment. The hearts were perfused with 37℃ Krebs-Henseleit buffer balanced with gas mixture(O2: CO2=95%: 5%) at 70cmH2O(perfusion pressure). Cardial arrest was induced by St.Thomas crystal hyperpotassium cardioplegic solution. Hearts in each groups were subjected to global ischemia at 37℃ for 45 min followed by 40 min reperfusion. Forty animals were randomly divided into 5 groups(Except for control group, different dosage of SFI were added into St.Thomas cardioplegic solution): group C(n=8, group control ), group SF1(n=8, the concentration of SFI was 1%), group SF5(n=8, the concentration was 5%), group SF10(n=8, the concentration was 10%), group SF15(n=8, the concentration was 15%). Coronary flow(CF), heart rate(HR), left ventricle developed pressure(LVDP) and ±dp/dtmax were monitored before ischemia(baseline value) and 5min, 10min, 20min, 40min after onset of reperfusion ( expressed as percentage of their baseline values). Coronary effluent was collected at above time for CK-MB determination. Electron microscope was used to observe the change of myocardial ultrastructure, and mitochondrial injury was assessed by morphologic score. Myocardial mitochondria was isolated by differential centrifugation. Ca2+ content of mitochondria was measured by atomic absorption spectrophotometry and the malondialdehyde (MDA) content of mitochondria was determinated by the method of Thibabituric Acid reaction (TBA).Results There were little difference in HR recovery among all groups(P>0.05). In group SF5 and SF10 , the recovery rate of CF, LVDP, ±dp/dtmax significantly increased, the CK-MB and MDA and Ca2+ level were greatly decreased and the score of mitochondrial morphology were better than control group(P<0.05 or P<0.01). On the contrary, in group SF15 such indices were worse even than control group (P<0.05 or P<0.01).Conclusions 1. SFI have obvious protective effect on isolated rabbit heart at the concentration 5% and 10%. 2. High concentration (15%) may cause mitochondria Ca2+ overload and have negative impact.