Mertes P M, el-Abbassi K, Jaboin Y, Michel C, Beck B, Pinelli G, Carteaux J P, Villemot J P, Burlet C
Laboratoire de Chirurgie Expérimentale, Faculté de Medecine, Université Nancy I, France.
J Mol Cell Cardiol. 1996 Sep;28(9):1995-2004. doi: 10.1006/jmcc.1996.0192.
An attempt to determine the consequences of prolonged ischemia on simultaneous regional changes in norepinephrine (NE) and neuropeptide Y (NPY) interstitial myocardial concentrations in a pig model in vivo was made. The aim of the authors was to investigate further the mechanism of the major NE release previously observed in perfused hearts preserved using a Langendorff technique. Regional myocardial ischemia was induced by ligation of the left anterior descending coronary artery (LAD) in ten anesthetized pigs. NE and NPY release was studied using interstitial microdialysis, a technique initially used to monitor neurotransmitter kinetics in brain dialysate samples. Four dialysis probes were implanted into the left ventricular wall of the beating heart. Two were implanted into the ischemic region (LAD) (for NE and NPY determinations, respectively) and the remaining two into the non-ischemic left circumflex coronary artery region (LCX). Dialysate NE and NPY concentrations, as indices of interstitial myocardial NE and NPY concentrations, were measured by HPLC and RLA, respectively. A slight but significant increase in NPY levels was observed in both territories (LAD: from 190 +/- 27 to 349 +/- 62 pmol/l, LCX: 146 +/- 30 to 257 +/- 52 pmol/l) suggesting moderate stimulation of cardiac sympathetic nerve activity following LAD occlusion. On the contrary, a marked but progressive increase in NE release was observed in the ischemic region (from 8.8 +/- 1.0 to 251.4 +/- 44.8 nmol/l), when NE levels in the non-ischemic region remained stable (from 10.3 +/- 2.1 to 11.0 +/- 1.9 nmol/l). These results demonstrate the utility of regional in-vivo myocardial NE and NPY monitoring using microdialysis. The strong and sustained NE accumulation occurring in the ischemic region is consistent with the hypothesis of a local non-exocytotic metabolic NE release in case of prolonged myocardial ischemia, when exocytotic release remain only minimal as attested by the slight increase in NPY observed.
在猪体内模型中，尝试确定长时间缺血对去甲肾上腺素（NE）和神经肽Y（NPY）心肌间质浓度同时发生的局部变化的影响。作者的目的是进一步研究先前在使用Langendorff技术保存的灌注心脏中观察到的主要NE释放机制。通过结扎十只麻醉猪的左冠状动脉前降支（LAD）诱导局部心肌缺血。使用间质微透析研究NE和NPY释放，该技术最初用于监测脑透析液样本中的神经递质动力学。将四个透析探针植入跳动心脏的左心室壁。两个植入缺血区域（LAD）（分别用于测定NE和NPY），其余两个植入非缺血的左旋冠状动脉区域（LCX）。分别通过HPLC和RLA测量透析液NE和NPY浓度，作为心肌间质NE和NPY浓度的指标。在两个区域均观察到NPY水平有轻微但显著的升高（LAD：从190±27至349±62 pmol/l，LCX：从146±30至257±52 pmol/l），表明LAD闭塞后心脏交感神经活动受到适度刺激。相反，在缺血区域观察到NE释放有显著但逐渐增加（从8.8±1.0至251.4±44.8 nmol/l），而非缺血区域的NE水平保持稳定（从10.3±2.1至11.0±1.9 nmol/l）。这些结果证明了使用微透析进行局部体内心肌NE和NPY监测的实用性。在缺血区域发生的强烈且持续的NE积累与长时间心肌缺血时局部非胞吐性代谢性NE释放的假设一致，此时胞吐性释放仅为最小程度，如观察到的NPY轻微增加所证明。
