Koning M M, Gho B C, van Klaarwater E, Opstal R L, Duncker D J, Verdouw P D
Laboratory for Experimental Cardiology, Erasmus University Rotterdam, The Netherlands.
Circulation. 1996 Jan 1;93(1):178-86. doi: 10.1161/01.cir.93.1.178.
Rapid ventricular pacing reduces the incidence of ventricular arrhythmias during a subsequent sustained period of ischemia and reperfusion. We investigated whether rapid ventricular pacing also limits myocardial infarction and determined the role of KATP+ channels in the protection afforded by ventricular pacing.
Myocardial infarction was produced by a 60-minute coronary artery occlusion in open chest pigs. Infarct size of pigs subjected to 10 minutes of ventricular pacing at 200 beats per minute followed by 15 minutes of normal sinus rhythm before the occlusion (79 +/- 3% of the area at risk, mean +/- SEM) was not different from control infarct size (84 +/- 2%). Thirty-minute pacing followed by 15-minute sinus rhythm resulted in modest reductions in infarct size (71 +/- 2%, P<.05 versus control). Thirty minutes of pacing immediately preceding the occlusion without intervening sinus rhythm resulted in considerable limitation of infarct size (63 +/- 4%, P<.05), which was abolished by pretreatment with the KATP+ channel blocker glibenclamide (78 +/- 4%, P=NS). KATP+ channel activation did not appear to involve ischemia: (1) myocardial endocardial/epicardial blood flow ratio was 1.07 +/- 0.08, (2) phosphocreatine and ATP levels and arterial-coronary venous differences in pH and PCO2 were unchanged, (3) end-systolic segment length did not increase and postsystolic shortening was not observed during pacing, and (4) systolic shortening recovered immediately to baseline levels and coronary reactive hyperemia was absent after cessation of pacing. Administration of glibenclamide after 30 minutes of pacing at the onset of 15 minutes of normal sinus rhythm did not attenuate the protection (73 +/- 3%, P<.05 versus control), suggesting the KATP+ channels did not contribute to the moderate degree of protection that was still present 15 minutes after cessation of pacing.
Rapid ventricular pacing protects the myocardium against infarction via nonischemic KATP+ channel activation. Continued activation of KATP+ channels does not appear mandatory for the protection that is still present 15 minutes after cessation of pacing.
快速心室起搏可降低随后持续缺血和再灌注期间室性心律失常的发生率。我们研究了快速心室起搏是否也能限制心肌梗死，并确定了ATP敏感性钾（KATP+）通道在心室起搏所提供的保护作用中的作用。
通过开胸猪冠状动脉闭塞60分钟制造心肌梗死。在闭塞前，以每分钟200次的频率进行10分钟心室起搏，随后15分钟正常窦性心律，其梗死面积（占危险区域面积的79±3%，均值±标准误）与对照梗死面积（84±2%）无差异。30分钟起搏后接15分钟窦性心律，梗死面积适度减小（71±2%，与对照相比P<0.05）。在闭塞前立即进行30分钟起搏且无中间窦性心律，梗死面积显著受限（63±4%，P<0.05），而用KATP+通道阻滞剂格列本脲预处理可消除这种保护作用（78±4%，P=无显著差异）。KATP+通道激活似乎不涉及缺血：（1）心肌心内膜/心外膜血流比值为1.07±0.08，（2）磷酸肌酸和ATP水平以及动脉-冠状静脉pH和PCO2差值未改变，（3）起搏期间收缩末期节段长度未增加且未观察到收缩后缩短，（4）起搏停止后收缩期缩短立即恢复至基线水平且无冠状动脉反应性充血。在15分钟正常窦性心律开始时，30分钟起搏后给予格列本脲并未减弱保护作用（73±3%，与对照相比P<0.05），这表明KATP+通道对起搏停止15分钟后仍存在的中度保护作用无贡献。
快速心室起搏通过非缺血性激活KATP+通道保护心肌免受梗死。起搏停止15分钟后仍存在的保护作用似乎并不依赖于KATP+通道的持续激活。
