离体工作大鼠心脏中糖尿病对缺血/再灌注及预处理反应的演变

The evolution of diabetic response to ischemia/reperfusion and preconditioning in isolated working rat hearts.

作者信息

Tosaki A, Engelman D T, Engelman R M, Das D K

机构信息

University of Connecticut Health Center, School of Medicine, Farmington 06030-1110, USA.

出版信息

Cardiovasc Res. 1996 Apr;31(4):526-36.

PMID:8689644

Abstract

OBJECTIVE

Studies have shown that the diabetic heart exhibits abnormalities in cellular ion transport, which can affect susceptibility to reperfusion-induced ventricular fibrillation (VF), tachycardia (VT) and functional derangements. It has been shown that "preconditioning" renders the heart very resistant to a subsequent prolonged ischemic episode. This phenomenon has been extensively studied in healthy myocardium, but such a study has not been previously done in diseased (hypertrophic or myopathic) hearts.

METHODS

We studied the incidence of reperfusion-induced VF, VT, cardiac function, and ion shifts (Na+, K+, Ca2+, and Mg2+) induced by ischemia/reperfusion in isolated hearts from rats with streptozotocin-induced diabetes. Following 2, 4, 6, and 8 weeks of diabetes, hearts were isolated and subjected to 30 min global ischemia followed by reperfusion.

RESULTS

In the 2-week diabetic group the total incidence of VF and VT was reduced from their non-diabetic age-matched control value of 100 and 100% to 42 (P < 0.05) and 42% (P < 0.05), respectively. Such a reduction in the incidence of VF and VT was not observed with progressive diabetes (4, 6, and 8 weeks). In the 2-week diabetics, the reduction in the VF and VT was reflected in the improvement of postischemic function, the reduction of ischemia and reperfusion-induced Na+ and Ca2+ gains, and the prevention in K+ and Mg2+ loss. This diabetes-induced initial protection was not seen in the 4- and 6-week diabetics, and a deterioration of postischemic function was observed in the 8-week diabetics. Four cycles of preconditioning, each consisting of 5 min ischemia followed by 10 min reperfusion, failed to reduce the incidence of VF and VT, improve cardiac function, and prevent ion shifts induced by 30 min ischemia followed by 30 min reperfusion in 4- and 8-week diabetics.

CONCLUSIONS

In the early phase of diabetes the heart is more resistant to ischemia/reperfusion than the non-diabetic heart. Preconditioning does not afford protection against a prolonged period of ischemia in diabetics, indicating that preconditioning may be a "healthy heart phenomenon".

摘要

目的

研究表明，糖尿病心脏在细胞离子转运方面存在异常，这可能会影响其对再灌注诱导的心室颤动（VF）、心动过速（VT）及功能紊乱的易感性。研究显示，“预处理”可使心脏对随后的长时间缺血发作具有很强的抵抗力。这一现象已在健康心肌中得到广泛研究，但此前尚未在患病（肥厚性或肌病性）心脏中进行此类研究。

方法

我们研究了链脲佐菌素诱导的糖尿病大鼠离体心脏中，再灌注诱导的VF、VT发生率、心脏功能以及缺血/再灌注诱导的离子变化（Na⁺、K⁺、Ca²⁺和Mg²⁺）。糖尿病持续2、4、6和8周后，分离心脏并进行30分钟全心缺血，随后再灌注。

结果

在糖尿病2周组中，VF和VT的总发生率从非糖尿病年龄匹配对照组的100%和100%分别降至42%（P<0.05）和42%（P<0.05）。随着糖尿病病程进展（4、6和8周），未观察到VF和VT发生率的这种降低。在糖尿病2周组中，VF和VT发生率的降低反映在缺血后功能的改善、缺血和再灌注诱导的Na⁺和Ca²⁺增加的减少以及K⁺和Mg²⁺丢失的预防上。在糖尿病4周和6周组中未观察到这种糖尿病诱导的初始保护作用，而在糖尿病8周组中观察到缺血后功能恶化。在糖尿病4周和8周组中，四个预处理周期（每个周期包括5分钟缺血后接10分钟再灌注）未能降低VF和VT的发生率、改善心脏功能以及预防30分钟缺血后接30分钟再灌注诱导的离子变化。