Forrat R, de Lorgeril M, Hadour G, Sebbag L, Delaye J, Ferrera R
Explorations Fonctionnelles Cardiorespiratoires et Métaboliques, CHU de Saint-Etienne, Hôpital Cardiologique, Lyon, France.
J Mol Cell Cardiol. 1998 Sep;30(9):1889-95. doi: 10.1006/jmcc.1998.0754.
In this study, we examined whether chronic severe diabetes may affect ischaemic and post-ischaemic regional myocardial dysfunction in vivo in the dog. Diabetes was chemically induced in randomized animals and major metabolic alterations were observed confirming the severity and chronicity of the diabetes. After 70 days, halothane-anaesthetized dogs underwent a 20-min coronary occlusion, followed by reperfusion. During ischaemia, global left ventricle function (dP/dtmax) was more altered (P<0.005) in diabetics ( n=10) than in controls (n=10), whereas area-at-risk (29+/-2.5% of the left ventricle in diabetics v 32.4+/-1.9% in controls) and ischaemic subendocardial myocardial blood flow (radioactive microsphere technique, 0.11+/-0.02 v 0.10+/-0.03 ml/min/g) were similar. During reperfusion, both groups developed significant (P<0.05) regional myocardial dysfunction (somomicrometry, 41+/-14% of baseline in controls and 66+/-8% in diabetics), whereas the difference between groups was not significant. No dog of either group developed myocardial cell necrosis on tissue histology. Multivariate analyses, including the severity of prior ischaemia and the occurrence of ventricular fibrillation as covariables, confirmed that myocardial stunning was not increased in diabetics, although ischaemia was clearly less-well-tolerated in diabetic dogs as global (dP/dtmax) as well as regional myocardial function were significantly (P<0.05) more altered in diabetics during ischaemia. Whilst alteration of arachidonate and cholesterol metabolism may partly explain this apparent paradox, further studies are required to resolve this issue.
在本研究中，我们检测了慢性重度糖尿病是否会影响犬体内缺血及缺血后局部心肌功能障碍。对随机分组的动物进行化学诱导糖尿病，观察到主要代谢改变，证实了糖尿病的严重程度和慢性病程。70天后，用氟烷麻醉犬只，使其冠状动脉闭塞20分钟，随后再灌注。在缺血期间，糖尿病犬（n = 10）的整体左心室功能（dP/dtmax）较对照组（n = 10）改变更大（P<0.005），而危险面积（糖尿病犬左心室的29±2.5%，对照组为32.4±1.9%）和缺血性心内膜下心肌血流（放射性微球技术，0.11±0.02对0.10±0.03 ml/min/g）相似。在再灌注期间，两组均出现显著（P<0.05）的局部心肌功能障碍（心肌测量法，对照组为基线的41±14%，糖尿病犬为66±8%），但两组间差异不显著。两组均无犬只在组织学检查中出现心肌细胞坏死。多变量分析，包括将先前缺血的严重程度和心室颤动的发生作为协变量，证实糖尿病犬的心肌顿抑并未增加，尽管糖尿病犬对缺血的耐受性明显较差，因为在缺血期间糖尿病犬的整体（dP/dtmax）及局部心肌功能改变更为显著（P<0.05）。虽然花生四烯酸和胆固醇代谢的改变可能部分解释了这一明显的矛盾现象，但仍需要进一步研究来解决这一问题。
