Schäfer Ulrich, Kurz Thomas, Jain Deepak, Hartmann Franz, Dendorfer Andreas, Tölg Ralph, Raasch Walter, Dominiak Peter, Katus Hugo, Richardt Gert
Medizinische Klinik II, Universitätsklinik Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
Basic Res Cardiol. 2002 Sep;97(5):399-408. doi: 10.1007/s003950200049.
Reopening of the infarct-related coronary artery is the treatment of choice in the clinical setting of acute myocardial infarction. Nevertheless the removal of the total occlusion obtained either by thrombolysis or by primary angioplasty is followed by the ischemia/reperfusion sequelae. One of many proposed mechanisms playing a role in ischemia/reperfusion damage is a persistent increase in vasoconstrictor tone, which reduces cardiac function and impairs myocardial blood flow during primary percutaneous coronary intervention in acute myocardial infarction (PAMI).
To investigate early neurohumoral changes during PAMI we enrolled 18 patients, who were collated to 13 patients with stable angina undergoing elective PTCA. To evaluate angiotensin II (AngII), endothelin-1 (ET-1), vasopressin (AVP), norepinephrine (NE), troponin T (TNT), creatinephosphate kinase (CPKM) and isoenzyme MB (CPKMB), we collected blood from the pulmonary artery before and immediately after the infarct-related artery (IRA; TIMI 0 --> 2-3) or culprit lesion revascularization. Hemodynamic and angiographic LV-function parameters were compared to biochemical data. Corrected TIMI-frame count (CTFC) was used as an index of coronary blood flow and correlated to the biochemical measurements.
CTFC in the IRA correlated inversely (p = 0.03; r = -0.51) with left ventricular ejection fraction measured after 10 days, and positively (p = 0.03; r = 0.54) with the maximal amount of LDH released after onset of AMI. There was an abrupt and long lasting rise in ET-1 (+65 %; p < 0.001) and an instant short lasting increase in AVP (+37 %; p < 0.05), whereas NE concentrations were elevated prior to PAMI and remained elevated during reperfusion. Correlations with CTFC were found for ET-1 (p = 0.01; r = 0.61) and NE (p = 0.01; r = 0.58) during reperfusion. The extent of left ventricular dysfunction correlated with the concentrations of AVP and NE during reperfusion.
There is evidence for a distinct pattern of neurohumoral activation during early reperfusion in acute myocardial infarction. In particular, we documented substantial increases in AVP and ET-1. Left ventricular wall-stress appears to be involved in the release of AVP. Elevated levels of ET-1 and NE are associated with impaired angiographic reperfusion and increased myocardial damage after mechanical recanalization.
在急性心肌梗死的临床治疗中，开通梗死相关冠状动脉是首选治疗方法。然而，无论是通过溶栓还是直接血管成形术实现的完全闭塞病变的开通，都会引发缺血/再灌注后遗症。在缺血/再灌注损伤中起作用的众多机制之一是血管收缩张力持续增加，这在急性心肌梗死直接经皮冠状动脉介入治疗（PAMI）期间会降低心脏功能并损害心肌血流。
为了研究PAMI期间早期神经体液变化，我们纳入了18例患者，并将其与13例接受择期PTCA的稳定型心绞痛患者进行对照。为了评估血管紧张素II（AngII）、内皮素-1（ET-1）、血管加压素（AVP）、去甲肾上腺素（NE）、肌钙蛋白T（TNT）、肌酸磷酸激酶（CPKM）和同工酶MB（CPKMB），我们在梗死相关动脉（IRA；TIMI 0至2 - 3级）或罪犯病变血运重建前及重建后立即从肺动脉采集血液。将血流动力学和血管造影左心室功能参数与生化数据进行比较。校正的TIMI帧数计数（CTFC）用作冠状动脉血流指标，并与生化测量值相关联。
IRA中的CTFC与10天后测量的左心室射血分数呈负相关（p = 0.03；r = -0.51），与急性心肌梗死发作后释放的最大乳酸脱氢酶量呈正相关（p = 0.03；r = 0.54）。ET-1出现突然且持久的升高（+65%；p < 0.001），AVP出现即刻且短暂的升高（+37%；p < 0.05），而NE浓度在PAMI前升高，并在再灌注期间保持升高。在再灌注期间，发现ET-1（p = 0.01；r = 0.61）和NE（p = 0.01；r = 0.58）与CTFC相关。左心室功能障碍的程度与再灌注期间AVP和NE的浓度相关。
有证据表明急性心肌梗死早期再灌注期间存在独特的神经体液激活模式。特别是，我们记录到AVP和ET-1大幅增加。左心室壁应力似乎参与了AVP的释放。ET-1和NE水平升高与血管造影再灌注受损以及机械再通后心肌损伤增加有关。
