Myocardial infarction and heart failure in the db/db diabetic mouse
Myocardial infarction and heart failure in the db/db diabetic mouse
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DOI：
10.1152/ajpheart.00583.2005
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发表时间：
2006-01-01
影响因子：
4.8
通讯作者：
Lefer, DJ
中科院分区：
文献类型：
--
作者：
Greer, JJM;Ware, DP;Lefer, DJ
临床研究报告称，在校正了所有其他危险因素后，糖尿病患者的心肌梗死发生率和严重程度明显高于非糖尿病患者。大多数研究心肌缺血再灌注损伤的病理生理学的研究都集中在其他健康的动物身上。目前，有关糖尿病动物心力衰竭病理生理的实验研究较少。我们假设db/db糖尿病小鼠心肌再灌注损伤的严重程度和充血性心力衰竭的发展将显著增强。因此，我们研究了体内心肌缺血和再灌注的不同持续时间对db/db糖尿病小鼠心力衰竭发生率的影响。非糖尿病和db/db糖尿病小鼠(10wk龄)行左冠状动脉闭塞30、45或60min，再灌注28d。非糖尿病小鼠心肌缺血30分钟再灌注24小时存活率为100%，非糖尿病小鼠心肌缺血45分钟存活率为88%。相比之下，db/db糖尿病小鼠在心肌缺血30分钟后存活率为53%，而db/db小鼠在心肌缺血45分钟后存活率为44%。与28天的随访期相比，非糖尿病小鼠的存活时间延长并没有明显减弱，所有组的存活率都达到了90%。与假手术对照组相比，db/db小鼠在心肌缺血30分钟和45分钟后的存活时间显著减少。此外，我们观察到db/db小鼠在45分钟的心肌缺血和28天的再灌流后，左室显著扩张、心肌肥厚和心脏收缩功能障碍。在接受45分钟心肌缺血的非糖尿病小鼠中，我们没有观察到任何左心室内径或缩短率的变化。这些研究为研究db/db糖尿病小鼠急性心肌梗死后继发心力衰竭提供了一个可行的实验模型系统。
Clinical studies have reported that the incidence and severity of myocardial infarction is significantly greater in diabetics compared with nondiabetics after correction for all other risk factors. The majority of studies investigating the pathophysiology of myocardial ischemia-reperfusion injury have focused on otherwise healthy animals. At present, there is a paucity of experimental investigations on the pathophysiology of heart failure in diabetic animals. We hypothesized that the severity of myocardial reperfusion injury and the development of congestive heart failure would be markedly enhanced in the db/db diabetic mouse. Accordingly, we studied the effects of varying durations of in vivo myocardial ischemia and reperfusion on the incidence of heart failure in db/db diabetic mice. Nondiabetic and db/ db diabetic mice (10 wk of age) were subjected to 30, 45, or 60 min of left coronary artery occlusion and 28 days of reperfusion. Survival at 24 h of reperfusion was 100% in nondiabetic mice subjected to 30 min of myocardial ischemia and 88% in nondiabetic mice subjected to 45 min of myocardial ischemia. In contrast, survival was 53% in db/ db diabetic mice subjected to 30 min of myocardial ischemia and 44% in db/ db mice after 45 min of myocardial ischemia. Prolonged survival in nondiabetic mice was not significantly attenuated when compared during the 28-day follow-up period with all groups experiencing >90% survival. Prolonged survival was significantly decreased in db/ db mice after both 30 and 45 min of myocardial ischemia compared with sham controls. Furthermore, we observed a significant degree or left ventricular dilatation, cardiac hypertrophy, and cardiac contractile dysfunction in db/ db mice subjected to 45 min of myocardial ischemia and 28 days reperfusion. In nondiabetic mice subjected to 45 min of myocardial ischemia, we failed to observe any changes in left ventricular dimensions or fractional shortening. These studies provide a feasible experimental model system for the investigation of heart failure secondary to acute myocardial infarction in the db/ db diabetic mouse.