Wang S Y, Friedman M, Johnson R G, Zeind A J, Sellke F W
Department of Surgery, Beth Israel Hospital, Boston, Mass. 02215, USA.
J Thorac Cardiovasc Surg. 1995 Oct;110(4 Pt 1):1073-82. doi: 10.1016/s0022-5223(05)80177-1.
The purpose of the present study was to examine the role of adenosine triphosphate-sensitive potassium channels in mediating the coronary hyperemic response after crystalloid cardioplegia. Thirteen pigs were placed on normothermic cardiopulmonary bypass support. Hearts were arrested with cold (4 degrees C) crystalloid ([K+] 25 mmol/L) cardioplegic solution for 60 minutes. In seven of these pigs, hearts were then reperfused for 60 minutes with warm blood, and the animal was separated from cardiopulmonary bypass. The in vivo responses to the intracoronary administration of the K+ adenosine triphosphate channel blocker glibenclamide (50 gm/kg per minute) or the K+ adenosine triphosphate channel opener pinacidil (2 gm/kg per minute) were evaluated before cardiopulmonary bypass (baseline) and after 2 minutes and 60 minutes of reperfusion in the cardioplegia-reperfusion group. Under baseline conditions, glibenclamide and pinacidil induced a respective decrease and increase in coronary blood flow and an increase and a decrease in coronary vascular resistance. Coronary responses to glibenclamide and pinacidil were markedly enhanced after 2 minutes or 60 minutes of postcardioplegia reperfusion. In vitro responses of coronary arterioles (90 to 180 microns) were examined in a pressurized, no-flow state with video microscopy. The contractile response of coronary arterioles to glibenclamide and the relaxation response to pinacidil were significantly enhanced 2 minutes or 60 minutes after reperfusion (all p < 0.05 versus control). The response to pinacidil was markedly inhibited by glibenclamide, which confirms these antagonistic effects on K+ adenosine triphosphate channels. Decreased tissue concentrations of adenosine triphosphate in the coronary arterial smooth muscle and myocardium were observed after cardioplegia and persisted for up to 60 minutes of reperfusion (both p < 0.05 versus control). These results suggest that coronary hyperemia associated with postischemic cardioplegia is mediated in part by activation of K+ adenosine triphosphate channels in the coronary microcirculation.
本研究的目的是探讨三磷酸腺苷敏感性钾通道在介导晶体停搏液灌注后冠状动脉充血反应中的作用。13只猪接受常温体外循环支持。心脏用冷（4℃）晶体（[K⁺]25 mmol/L）停搏液停搏60分钟。其中7只猪的心脏随后用温血再灌注60分钟，动物脱离体外循环。在体外循环前（基线）以及停搏液再灌注组再灌注2分钟和60分钟后，评估冠状动脉内给予钾离子三磷酸腺苷通道阻滞剂格列本脲（50 μg/kg每分钟）或钾离子三磷酸腺苷通道开放剂匹那地尔（2 μg/kg每分钟）后的体内反应。在基线条件下，格列本脲和匹那地尔分别导致冠状动脉血流减少和增加，以及冠状动脉血管阻力增加和减少。停搏液再灌注2分钟或60分钟后，冠状动脉对格列本脲和匹那地尔的反应明显增强。在加压无血流状态下，用视频显微镜检查冠状动脉小动脉（90至180微米）的体外反应。再灌注2分钟或60分钟后，冠状动脉小动脉对格列本脲的收缩反应和对匹那地尔的舒张反应明显增强（与对照组相比，所有p<0.05）。格列本脲明显抑制了对匹那地尔的反应，这证实了对钾离子三磷酸腺苷通道的这些拮抗作用。停搏液灌注后观察到冠状动脉平滑肌和心肌中三磷酸腺苷的组织浓度降低，并在再灌注长达60分钟时持续存在（与对照组相比，两者p<0.05）。这些结果表明，与缺血后停搏液灌注相关的冠状动脉充血部分是由冠状动脉微循环中钾离子三磷酸腺苷通道的激活介导的。
