ACUTE AND CHRONIC EFFECTS OF TRANSIENT MYOCARDIAL-ISCHEMIA ON SYMPATHETIC-NERVE ACTIVITY, DENSITY, AND NOREPINEPHRINE CONTENT
ACUTE AND CHRONIC EFFECTS OF TRANSIENT MYOCARDIAL-ISCHEMIA ON SYMPATHETIC-NERVE ACTIVITY, DENSITY, AND NOREPINEPHRINE CONTENT
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DOI：
10.1016/s0008-6363(95)00039-9
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发表时间：
1995-08-01
影响因子：
10.8
通讯作者：
MICHAEL, C
中科院分区：
文献类型：
--
作者：
DAE, MW;OCONNELL, JW;MICHAEL, C
目的：交感神经系统对心肌功能有深远的影响，特别是在缺血时。然而，对于心肌缺血是否会对流经缺血区域的心肌交感神经造成损害，存在争议。为了进一步评估这些问题，我们评估了短暂性心肌缺血对交感神经功能和形态的急性和慢性影响。方法：对20只犬进行研究。在急性研究中（n = 9），我们在冠状动脉闭塞和再灌注期间对I-123 metaiodobenzylguanidine （MIBG）冲洗进行了连续动态成像，并用铊-201评估了剩余心肌灌注。对于慢性研究（n = 11），我们在短暂冠状动脉内球囊闭塞11天后评估交感神经的支配和灌注。影像学结果与心电图反应、组织学和组织去甲肾上腺素（NE）相关。结果：在急性研究中，冠状动脉闭塞期间缺血区域的局部MIBG洗脱比对照组增加了2倍以上（14.2 +/- 2.3 vs. 5.9 +/- 1.2%, P < 0.01）。与非缺血区域相比，缺血区域组织NE减少（335 +/- 162比751 +/- 190 ng/g， P < 0.01）。心肌灌注正常。在慢性研究中，9/11犬在球囊闭塞期间出现缺血性心电图改变，并发室性心律失常。在随访影像中，5/11的狗在坏死的心内膜下存活的心肌中表现出相对于锂离子降低的MIBG摄取，NE降低（对照组为226 +/- 77 ng/g，对照组为733 +/- 82 ng/g， P < 0.01），神经密度降低，神经支配程度大于疤痕（25.5 +/- 3.7 vs. 8.2 +/- 2.7%, P < 0.02）。11只狗中有6只显示正常的神经支配模式。结论：这些研究表明，在心肌缺血区域，交感神经受到急性影响，这是通过增强的MIBG区域冲洗检测到的。此外，慢性交感神经失支配可在没有跨壁心肌坏死的情况下发生；然而，短暂性缺血的发生并不能预测慢性去神经支配的发展。缺血的严重程度，如相关坏死的程度所证明的，似乎预示着慢性去神经支配。在没有跨壁梗死的情况下，导致交感神经慢性去神经支配的机制仍有待确定。
Objectives: The sympathetic nervous system has profound influences on myocardial function, particularly during ischemia. There is controversy, however, as to whether myocardial ischemia results in damage to myocardial sympathetic nerves coursing through the ischemic territory. To further evaluate these issues, we assessed the acute and chronic effects of transient myocardial ischemia on sympathetic nerve function and morphology. Methods: A total of 20 dogs were studied. For acute studies (n = 9), we performed serial dynamic imaging of I-123 metaiodobenzylguanidine (MIBG) washout during coronary occlusion and reperfusion, and assessed residual myocardial perfusion with thallium-201. For chronic studies (n = 11), we assessed sympathetic innervation and perfusion 11 days following a transient intracoronary balloon occlusion. Imaging results were correlated with electrocardiographic responses, histology, and tissue norepinephrine (NE). Results: In the acute studies, regional MIBG washout increased more than 2-fold in the ischemic territory compared to the control region during coronary occlusion (14.2 +/- 2.3 vs. 5.9 +/- 1.2%, P < 0.01). Tissue NE was reduced in the ischemic territory compared to the non-ischemic territory (335 +/- 162 vs. 751 +/- 190 ng/g, P < 0.01). Myocardial perfusion was normal. In the chronic studies, 9/11 dogs showed ischemic ECG changes during balloon occlusion, and developed ventricular arrhythmias. On follow-up imaging, 5/11 dogs showed reduced MIBG uptake relative to thallium, in viable myocardium overlying necrotic subendocardium, reduced NE (226 +/- 77 vs. 733 +/- 82 ng/g in control regions, P < 0.01), decreased nerve density, and a larger extent of denervation than scar (25.5 +/- 3.7 vs. 8.2 +/- 2.7%, P < 0.02). Six of 11 dogs showed normal innervation patterns. Conclusions: These studies suggest that the sympathetic nerves are acutely affected in regions of myocardial ischemia as detected by enhanced regional washout of MIBG. In addition, chronic sympathetic nerve denervation can occur in the absence of transmural myocardial necrosis; however, the occurrence of transient ischemia does not predict the development of chronic denervation. The severity of ischemia, as evidenced by the extent of the related necrosis, does appear to predict chronic denervation. The mechanisms leading to chronic denervation of sympathetic nerves in the absence of transmural infarction remain to be defined.