Cleveland J C, Meldrum D R, Rowland R T, Banerjee A, Harken A H
University of Colorado Health Sciences Center, Department of Surgery, Denver 80262, USA.
J Mol Cell Cardiol. 1997 Jan;29(1):175-82. doi: 10.1006/jmcc.1996.0262.
Evidence supports the involvement of adenosine receptor stimulation and activation of K(ATP) channels in ischemic preconditioning of human myocardium. It is unknown, however, whether protection mediated by adenosine receptors is dependent upon the K(ATP) channel in the human heart. The purpose of this study was to determine whether adenosine-mediated protection against a simulated ischemia-reperfusion injury in human myocardium is dependent upon K(ATP) channels. Isolated human right atrial trabeculae were placed in tissue baths at 37 degrees C, oxygenated with a modified Tyrode solution, and field stimulated at 1 Hz. Trabeculae were subjected to 45 min of normothermic simulated ischemia (hypoxic, substrate-free buffer with pacing at 3 Hz.) and 60 min of reperfusion (I/R trabeculae). Trabeculae were preconditioned with simulated ischemia (IPC trabeculae) or adenosine receptor stimulation (adenosine, 125 micromol/l) for 5 min (ADO trabeculae) prior to simulated ischemic-reperfusion injury. Inhibition of the K(ATP) channel with glibenclamide (10 micromol/l) was combined with adenosine pretreatment (ADO+GLI trabeculae) or alone (GLI trabeculae) prior to simulated ischemic-reperfusion injury. Developed force (DF) at end reperfusion (mean+/-S.E.) was compared to baseline developed force, and tissue creatine kinase (CK) activity at end reperfusion was measured. I/R trabeculae showed 27+/-2% of baseline DF, whereas IPC trabeculae or ADO trabeculae showed 50+/-4% and 43+/-3% of baseline DF, respectively. ADO+GLI trabeculae showed 25+/-2% and GLI trabeculae showed 23+/-4% of baseline DF. Tissue CK activity was enhanced in the IPC and ADO trabeculae (433+/-63 U/g wet myocardium, and 415+/-28 U/g wet myocardium, respectively). I/R trabeculae had 196+/-26 U/g wet myocardium and ADO+GLI trabeculae had 277+/-38 U/g wet myocardium at end reperfusion. The results suggest that ischemic preconditioning and adenosine receptor stimulation confer functional protection against simulated ischemic-reperfusion, and adenosine mediated protection is eliminated by K(ATP) channel inhibition in human myocardium.
有证据支持腺苷受体刺激和K(ATP)通道激活参与人类心肌的缺血预处理。然而，尚不清楚腺苷受体介导的保护作用是否依赖于人类心脏中的K(ATP)通道。本研究的目的是确定腺苷介导的对人类心肌模拟缺血再灌注损伤的保护作用是否依赖于K(ATP)通道。将分离的人类右心房小梁置于37℃的组织浴中，用改良的台氏液进行氧合，并以1Hz进行场刺激。小梁先进行45分钟的常温模拟缺血（缺氧、无底物缓冲液，3Hz起搏）和60分钟的再灌注（I/R小梁）。在模拟缺血再灌注损伤之前，小梁用模拟缺血（IPC小梁）或腺苷受体刺激（腺苷，125μmol/L）预处理5分钟（ADO小梁）。在模拟缺血再灌注损伤之前，用格列本脲（10μmol/L）抑制K(ATP)通道，并与腺苷预处理联合（ADO+GLI小梁）或单独使用（GLI小梁）。将再灌注结束时的舒张末期力（DF）（平均值±标准误）与基线舒张末期力进行比较，并测量再灌注结束时的组织肌酸激酶（CK）活性。I/R小梁显示为基线DF的27±2%，而IPC小梁或ADO小梁分别显示为基线DF的50±4%和43±3%。ADO+GLI小梁显示为基线DF的25±2%，GLI小梁显示为基线DF的23±4%。组织CK活性在IPC和ADO小梁中增强（分别为433±63U/g湿心肌和415±28U/g湿心肌）。再灌注结束时，I/R小梁的组织CK活性为196±26U/g湿心肌，ADO+GLI小梁为277±38U/g湿心肌。结果表明，缺血预处理和腺苷受体刺激可对模拟缺血再灌注提供功能保护，而腺苷介导的保护作用在人类心肌中可被K(ATP)通道抑制消除。
