Cardioprotective Effect Of Remote Ischemic Post-conditioning

Objective To explore the cardioprotective effect and related mechanism of remote ischemic post-conditioning(RIPC) in animal trial and clinical study.Methods 1. Animal trial:30 healthy male Sprague–Dawley rats were randomly divided into three groups: A group( sham operation group,n=10)thoracotomy without ligation, threading and inserted in the left anterior descending artery( LAD);B group(remote ischemic post-conditioning group,n=10) receiving RIPC immediately after 60 minutes’ ligation of LAD and reperfusion for 120 minutes before chest closure; C group(Ischemia/Reperfusion group, n=10) receiving ligation of LAD for 60 minutes and reperfusion for 120 minutes before chest closure. Continuous ECG was monitored during the operation. We recorded the I lead ECG 180 minutes after threading in sham operation group and 120 minutes after reperfusion of LAD in RIPC group and I/R group. Blood samples in sham group were obtained 180 minutes after threading and inserted in the LAD. Other blood samples in RIPC group and I/R group were obtained 180 minutes after ligating the LAD. Blood samples centrifuged was used for mensurating the cardiac troponin I(c Tn I), creatine kinase isoenzyme MB(CK-MB) and stromal cell-derived factor 1α(SDF-1α).2. Clinical study: 42 cases of patients with acute ST segment elevation myocardial infarction were randomly divided into 2 groups:A group( PCI+RIPC group, n=20) receiving RIPC in 5 minutes after PCI.B group(PCI group, n=22) just receiving conventional emergency PCI.ECG was recorded before and 2 hours after the PCI for all patients, and then we record the complete ST resolutions in 2 groups. Blood samples for CK-MB and SDF-1α in all patients were taken at predetermined time. All patients received Doppler ultrasound examination 7 days after PCI, and then we recorded the left ventricular ejection fraction(LVEF)。Results 1. Animal trial:(1) ECG : There was no obvious change in ECG in sham group. The ST segment arched lift in RIPC group and PCI group after ligation of the LAD. There were more rats with ST segment drop≥50% in RIPC group than in PCI group after reperfusion for 120 minute(8 VS 4, 80% VS 40%,p>0/05).(2) Troponin I(c Tn I):Concentration of c Tn I in sham group, RIPC group and I/R group was(0.67±0.16)μg /L,(2.98±0.62)μg /L and(4.88±0.85) μg /L respectively. Levels of c Tn I were higher in RIPC group and I/R group compared with sham group(P<0.05). Compared with I/R group, levels of c Tn I were lower in RIPC group(P<0.05).(3)Creatine kinase isoenzyme MB(CK-MB): Concentration of CK-MB in sham group, RIPC group and I/R group was(108.60 ± 17.74)U/L,(567.60 ± 40.42)U/L and(761.30 ± 107.11)U/L respectively. Levels of CK-MB were higher in RIPC group and I/R group compared with sham group(P<0.05). Compared with I/R group, levels of CK-MB were lower in RIPC group(P<0.05).(4) SDF-1α:Concentration of SDF-1α in sham group, RIPC group and I/R group was(174.50±12.02)pg/ml,(313.40±45.13)pg/ml and(230.30±36.10)pg/ml respectively.Compared with sham group and I/R group, levels of SDF-1α were higher in RIPC group( P<0.05).Levels of SDF-1α were higher in I/R group than in sham group(P<0.05).2. Clinical study :(1) ECG : Compared with PCI group, more patients in PCI+RIPC group had ST segment drop≥50% and there was significant difference(16 VS 9, 80% VS 40.9%,P<0.05).(2)CK-MB: Patients in the I/R group presented with higher peak CK-MB compared with patients in the RIPC group, but there was no significant difference [(435.82±138.80) VS(407.80±117.62)U/L,P>0.05].The area under the curve of CK-MB in PCI+RIPC group was smaller than in PCI group, but there was no statistically significant difference [(10195±2589 VS(10817±2850),P>0.05)].(3) Doppler ultrasound :Compared with PCI group, LVEF was higher in PCI+ RIPC group, but there was no statistically significant difference((46.3±6.2)% VS(44.7±8.0)%,p>0.05).(4) SDF-1α:The levels of SDF-1α were no different at each predetermined time between PCI group and PCI+RIPC group(p>0.05).Conclusion 1. This animal trial indicates that remote ischemic post-conditioning may reduce myocardial necrosis through the SDF-1α.2. In the clinical study, remote ischemic post-conditioning seemed to fail to reduce the myocardial necrosis and improve the myocardial function significantly.