Chicco Adam J, Johnson Micah S, Armstrong Casey J, Lynch Joshua M, Gardner Ryan T, Fasen Geoff S, Gillenwater Cody P, Moore Russell L
Department of Integrative Physiology, University of Colorado at Boulder, Boulder, CO 80309, USA.
Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2432-7. doi: 10.1152/ajpheart.01301.2006. Epub 2007 Jan 19.
The present study was conducted to determine whether the infarct sparing effect of short-term exercise is dependent on the operation of the myocardial sarcolemmal ATP-sensitive K(+) (K(ATP)) channel. Adult male and female Sprague-Dawley rats were exercised on a motorized treadmill for 5 days. Twenty-four hours following the training or sedentary period, hearts were isolated and exposed to 1 h of regional ischemia followed by 2 h of reperfusion on a modified Langendorf apparatus in the presence or absence of the sarcolemmal K(ATP) channel antagonist HMR-1098 (30 microM). Following the ischemia-reperfusion protocol, infarct size was determined as a percentage of the total ischemic zone at risk (ZAR). Short-term exercise reduced infarct size by 24% in males (32 +/- 2% of ZAR; P < 0.01) and by 18% in females (26 +/- 2% of ZAR; P < 0.05). Sarcolemmal K(ATP) channel blockade abolished the training-induced cardioprotection in both males and females, increasing infarct size to 43 +/- 3% and 52 +/- 4% of ZAR, respectively. In the absence of HMR-1098, infarct size was significantly lower in sedentary females than in males (33 +/- 4% vs. 42 +/- 2% of ZAR, respectively; P < 0.01). However, the presence of HMR-1098 abolished this sex difference, increasing infarct size by 58% in the sedentary females (P < 0.01) but having no effect on infarct size in sedentary males. This study demonstrates that the sex-specific and exercise-acquired resistance to myocardial ischemia-reperfusion injury is dependent on sarcolemmal K(ATP) activity during ischemia.
本研究旨在确定短期运动的梗死灶保留效应是否依赖于心肌肌膜ATP敏感性钾（K(ATP)）通道的作用。成年雄性和雌性Sprague-Dawley大鼠在电动跑步机上运动5天。在训练期或静息期后的24小时，分离心脏，并在改良的Langendorff装置上进行1小时的局部缺血，随后在有或无肌膜K(ATP)通道拮抗剂HMR-1098（30微摩尔）的情况下进行2小时的再灌注。按照缺血-再灌注方案，将梗死灶大小确定为总缺血危险区（ZAR）的百分比。短期运动使雄性大鼠的梗死灶大小减少24%（占ZAR的32±2%；P<0.01），使雌性大鼠的梗死灶大小减少18%（占ZAR的26±2%；P<0.05）。肌膜K(ATP)通道阻断消除了训练诱导的雄性和雌性大鼠的心脏保护作用，使梗死灶大小分别增加到ZAR的43±3%和52±4%。在没有HMR-1098的情况下，静息雌性大鼠的梗死灶大小显著低于雄性大鼠（分别为ZAR的33±4%和42±2%；P<0.01）。然而，HMR-1098的存在消除了这种性别差异，使静息雌性大鼠的梗死灶大小增加了58%（P<0.01），但对静息雄性大鼠的梗死灶大小没有影响。本研究表明性别特异性以及运动获得的对心肌缺血-再灌注损伤的抵抗力取决于缺血期间肌膜K(ATP)的活性。
