Effect of hydromorphone postconditioning on myocardial ischemia-reperfusion injury in isolated rat hearts and the role of mitochondrial permeability transition pore / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effect of hydromorphone postconditioning on ischemiareperfusion (I/R) injury in isolated rat hearts and the role of mitochondial permeability transition pore (mPTP).Methods Male Sprague-Dawley rats, aged 2-3 months, weighing 250-320 g, were used in the study.The rats were heparinized and anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The hearts were excised, and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 36.5-37.5 ℃.Forty isolated rat hearts were randomly divided into 4 groups (n=10 each)using a random number table control group (group C), group I/R, hydromorphone postconditioning group (group H), and hydromorphone postconditioning + mPTP opener lonidamine group (group HL).Group C was continuously perfused with K-H solution for 120 min.Group I/R was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group I/R was perfused with K-H solution for another 30 min.Group H was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group H was perfused with K-H solution containing 0.3 μmol/L hydromorphone for 10 min, and then with K-H solution for 50 min.Group HL was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group HL was perfused with K-H solution containing 0.3 μmol/L hydromorphone and 30 μmol/L lonidamine for 10 min, and then with K-H solution for 50 min.At 30 min of equilibration (T0), and 30 and 60 min of reperfusion (T2,3), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP) , ±dp/dtmax, heart rate (HR), and coronary flow (CF) were measured.The concentrations of lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB) , and troponin-T (Tn-T) in the coronary effluent were determined at T0 and T3.The coronary effluent was collected at T0 and 15 min of reperfusion (T1),nicotinamide-adenine dinucleotide (NAD+) concentrations were measured using enzyme-linked immunosorbent assay to reflect the degree of mPTP opening.The myocardial infarct size was determined at T3 by TTC staining.Results Compared with group C, LVDP, HR, ±dp/dtmax and CF were significantly decreased, and LVEDP was increased at T2,3, and the concentrations of LDH, CK-MB and Tn-T in the coronary effluent, myocardial infarct size at T3, and NAD+ concentrations in the coronary effluent at T1 were increased in group I/R (P＜0.05).Compared with I/R and HL groups, LVDP, ±dp/dt CF and HR were significantly increased, and LVEDP was decreased at T2,3, and the concentrations of LDH, CK-MB and Tn-T in the coronary effluent, myocardial infarct size at T3, and NAD+ concentrations in the coronary effluent at T1 were decreased in group H (P＜0.05).Conclusion Hydromorphone postconditioning can reduce myocardial I/R injury in isolated rat hearts, and the mechanism is related to inhibition of mPTP opening.