Vogel W M, Apstein C S
Houseman Medical Research Center, Department of Pharmacology, Boston University School of Medicine, MA 02118-2394.
Circ Res. 1988 May;62(5):975-82. doi: 10.1161/01.res.62.5.975.
Hearts from rabbits with 8-16 weeks of alloxan-diabetes were compared with hearts from normal rabbits to determine whether diabetic myocardium is more sensitive to ischemic injury. In isolated buffer-perfused hearts, left ventricular developed pressure, diastolic pressure, time to peak pressure (TTPP), time to half-maximal relaxation (RT1/2), and positive and negative dP/dt were measured during generation of left ventricular filling curves before and after 90 minutes of low-flow ischemia. Hearts from diabetic rabbits (blood glucose, 384 +/- 28 mg/dl, mean +/- 95% confidence limits) had left ventricular developed and diastolic pressures similar to normal hearts but exhibited significant increases in TTPP and RT1/2 with decreased positive and negative dP/dt. Left ventricular chamber volume relative to heart mass was greater in diabetic than in normal hearts. Recovery of developed pressure after ischemia was similar in normal (41 +/- 16%) and diabetic hearts (47 +/- 13%). In diabetic hearts during recovery from ischemia, TTPP and R1/2 remained increased compared with normal hearts, with positive and negative dP/dt decreased compared with normal hearts, in proportion to the preischemic differences. After ischemia, high-energy phosphates were depleted to the same extent in normal and diabetic rabbits. In coronary ligation experiments, histochemically determined infarct size in diabetic rabbits after 30 minutes occlusion and 24 hours reperfusion was similar to that in normal rabbits when adjusted for a significantly smaller heart weight and a correspondingly smaller anatomic risk region in the diabetic animals. Thus, despite characteristic abnormalities of mechanical function in diabetic hearts, the severity of injury after ischemia with reperfusion was normal for diabetic hearts.
将8 - 16周的四氧嘧啶糖尿病兔的心脏与正常兔的心脏进行比较，以确定糖尿病心肌是否对缺血性损伤更敏感。在离体缓冲液灌注心脏中，在低流量缺血90分钟前后生成左心室充盈曲线期间，测量左心室舒张末压、舒张压、压力峰值时间（TTPP）、半最大舒张时间（RT1/2）以及正负dP/dt。糖尿病兔心脏（血糖，384±28mg/dl，均值±95%置信区间）的左心室舒张末压和舒张压与正常心脏相似，但TTPP和RT1/2显著增加，正负dP/dt降低。糖尿病心脏的左心室腔容积与心脏质量之比大于正常心脏。缺血后舒张末压的恢复在正常心脏（41±16%）和糖尿病心脏（47±13%）中相似。在缺血恢复过程中，糖尿病心脏的TTPP和R1/2仍高于正常心脏，正负dP/dt低于正常心脏，与缺血前差异成比例。缺血后，正常兔和糖尿病兔的高能磷酸盐消耗程度相同。在冠状动脉结扎实验中，经组织化学测定，糖尿病兔在闭塞30分钟和再灌注24小时后的梗死面积与正常兔相似，不过糖尿病动物的心脏重量明显较小，相应的解剖学风险区域也较小，已对此进行了校正。因此，尽管糖尿病心脏存在特征性的机械功能异常，但缺血再灌注后的损伤严重程度对于糖尿病心脏而言是正常的。
