Effect of hydromorphone postconditioning on myocardial ischemia-reperfusion injury in isolated rat hearts and the role of mitochondrial permeability transition pore
10.3760/cma.j.issn.0254-1416.2015.10.007
- VernacularTitle:氢吗啡酮后处理对大鼠心肌缺血再灌注损伤的影响及线粒体通透性转换孔在其中的作用:离体实验
- Author:
Qi CHEN
;
Ying ZHANG
;
Qing LIU
;
Miaoling LI
;
Fengxu YU
- Publication Type:Journal Article
- Keywords:
Hydromorphone;
Myocardial reperfusion injury;
Mitochondrial membrane transport proteins;
Postconditioning
- From:
Chinese Journal of Anesthesiology
2015;35(10):1197-1201
- CountryChina
- Language:Chinese
-
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.
