Comparison of the effects of ischemic preconditioning and limb remote ischemic postconditioning on inflammatory response during myocardial ischemia/reperfusion injury in rats in vivo

Abstract

Objective To compare the effects of ischemic preconditioning with limb remote ischemic postconditioning on inflammatory response during myocardial ischemia/reperfusion injury (I/RI) in rat in vivo.Methods Eighty male Sprague-Dawley rats weighing 250 g-350 g were randomly allocated into four groups (n=20 in each group):sham group (S group); ischemia reperfusion group (I/R group); ischemic preconditioning group (IPC group) and limb remote ischemic postconditioning group (LRIPOC group).In the groups other than the sham group,the myocardial ischemia reperfusion model was preparated by ligation of left anterior descending coronary artery for 30 min followed by 120 min reperfusion.During the process of ischemia and reperfusion,HR and MAP were recorded and the rate pressure product (RPP) at every measuring point was calculated as the index of myocardial oxygen consumption.In ten rats randomly selected from each group,the blood samples were collected from jugular vein at 30,60 min and 120 min after reperfusion.Then,serum concentrations of cardiac troponin I (cTnI),creatine kinase-MB (CK-MB),tumor necrosis factor αt (TNF-α),high mobility group box-1 protein (HMGB-1),intercellular adhesion molecule 1 (ICAM-1),interleukin1 (IL-1),IL-6 and IL-10 were all assessed.At the end of experiment,the infarct volumes were assessed by evans blue and triphenyltetrazolium chloride (TTC) staining.In another ten rats randomly selected from each group,the myocardial contents of TNF-α,HMGB-1,ICAM-1,IL-1,IL-6 and IL-10 in ischemic and non-ischemic regions were all measured after the rats were euthanized.Results The infarct volume was (72±9)％ in I/R group,(36±13)％ in IPC group,and (57±9)％ in LRIPOC group,respectively.And the serum concentration of cTnI was (0.99 ± 0.14) μg/L in I/R group,(0.37 ±0.08) μg/L in IPC group,and (0.54±0.07) μg/L in LRIPOC group,separately.In addition,the serum concentration of CK-MB was (110±13) μg/L in I/R group,(38±8) μ g/L in IPC group,and (45±6) μg/L in LRIPOC group,respectively.Compared to the I/R group,the infarct volume,serum concentrations of cTnI and CK-MB in both IPC and LRIPOC groups,the serum concentrations of TNF-α at 30,60 min and 120 min after reperfusion,serum concentrations of HMGB-1 at 60 min and 120 min,serum concentrations of ICAM-1,IL-1 and IL-6,myocardial concentrations of TNF-α,HMGB-1,ICAM-1,IL-1 and IL-6 in ischemic region,myocardial concentrations of TNF-α,ICAM-1,IL-1 and IL-6 in non-ischemic region in the IPC group,the serum concentrations of TNF-α at 30,60 min and 120 min after reperfusion,serum concentrations of HMGB-1,ICAM-1,IL-1 and IL-6 at 120 min after reperfusion,myocardial concentrations of TNF-α,HMGB-1,ICAM-1,IL-1 and IL-6 in both ischemic and non-ischemic regions in the LRIPOC group all significantly decreased(P＜0.05).As compared to the IPC group,the infarct volume,serum concentrations of cTnI and CK-MB,serum concentration of TNF-α at 60 min after reperfusion,serum concentrations of HMGB-1 and ICAM-1 at 120 min after reperfusion,myocardial concentrations of TNF-α,ICAM-1,IL-1 and IL-6 in ischemic region,myocardial concentrations of ICAM-1,IL-1 and IL-6 in non-ischemic region significantly increased in the LRIPOC group (P＜0.05).Conclusions The inflammation inhibiting effect of IPC is stronger than that of LRIPOC during myocardial I/RI,which may be one of reasons why the IPC can provide a more powerful protection against myocardial I/RI than the LRIPOC. Key words: Myocardial ischemia/reperfusion injury; Inflammatory response; Ischemic preconditioning; Limb remote ischemic postconditioning