Effects of preconditioning with different concentrations of nerve growth factor-β on ischemia-reperfusion injury in isolated rat hearts / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of preconditioning with different concentrations of nerve growth factor (NGF)-β on ischemia-reperfusion (I/R) injury in isolated rat hearts.Methods Thirty-two male Sprague-Dawley rats weighing 200-300 g,aged 8-10 weeks,were anesthetized with intraperitoneal 10％ chloral hydrate 300 mg/kg and heparin 500 IU/kg.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution oxygenated with 95％ O2-5％ CO2 at 37 ℃.After 10 min of stabilization,the isolated hearts were randomly divided into 4 groups (n=8 each) I/R group and different concentrations of NGF-β groups (groups N1-N3).In group I/R,the hearts were continuously perfused with K-H solution for 30 min,perfusion was suspended for 30 min followed by 120 min reperfusion.In groups N1-N3,the hearts were continuously perfused with K-H solution containing NGF-β0.1,0.2 and 0.4 ng/ml,respectively,for 20 min,followed by 10 min washout,and perfusion was suspended for 30 min followed by 120 min reperfusion.HR,Left ventricular end-diastolic pressure (LV-EDP),left ventricular developed pressure (LVDP) and + dp/dtmax were measured at the end of 10 min stabilization (baseline,T1),immediately before suspension of perfusion (T2),and at 5,30,60 and 120 min of reperfusion (T3-6).The activities of creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH) in the coronary effluent were measured at T1 and T3-T6.Myocardial tissues were obtained at T6 for detection of apoptosis (by TUNEL) and for microscopic examination.Apoptotic index (AI) was calculated.Results Compared with the baseline value at T1,LVDP and + dp/dtmax were significantly decreased,and LVEDP and activities of LDH and CK-MB were significantly increased at T3-T6 in each group,HR was significantly decreased in groups I/R,N2 and N3,while HR was significantly increased in group N1 (P ＜ 0.05).Compared with group I/R,LVDP,+ dp/dtmax and HR were significantly increased,LVEDP,activities of LDH and CK-MB and AI were significantly decreased in group N1,LVDP,+ dp/dtmax and HR were significantly decreased,and activities of LDH and CK-MB were significantly increased in group N2,and LVDP,+ dp/dtmax and HR were significantly decreased,and LVEDP,activities of LDH and CK-MB and Al were significantly increased in group N3 (P ＜ 0.05).LVDP,+ dp/dtmax and HR were significantly lower,and LVEDP,activities of LDH and CK-MB and AI were significantly higher in groups N2 and N3 than in group N1,and in group N3 than in group N2 (P ＜ 0.05).The pathologic changes were reduced in group N1 compared with I/R,N2 and N3 groups.Conclusion Preconditioning with the optimum concentration of NGF-β can at-tenuate I/R injury in isolated rat hearts,however,the injury can be aggravated when the concentration is too large,and inhibition of apoptosis in myocardial cells is involved in the mechanism of myocardial protection.