Hale S L, Kloner R A
Heart Institute, Good Samaritan Hospital, Los Angeles, CA 90017, USA.
Cardiovasc Res. 1998 Dec;40(3):502-7. doi: 10.1016/s0008-6363(98)00191-6.
Previously we observed that a large reduction in infarct size was attained by cooling the risk region of the heart, either before or early after the onset of a 30-min coronary artery occlusion. While this is a standard duration of ischemia used in the rabbit model of infarction, it may not reflect the situation of patients who are reperfused late. The effects of regional hypothermia with a longer duration of ischemia, and when the intervention is applied later, are unknown. This study tests the hypothesis that a local reduction in cardiac temperature protects myocardium during prolonged ischemia (2 h) even if begun well after coronary artery occlusion.
Anesthetized rabbits received 2 h of coronary artery occlusion and 3 h of reperfusion. Rabbits were randomly assigned to a treated group: topical myocardial cooling starting 30 min after coronary occlusion (n = 14), or control group, no intervention (n = 12). Myocardial temperature in the risk zone, hemodynamics and regional myocardial blood flow were measured.
Ischemic zone temperature was similar in both groups at 30 min post occlusion, but the cooling maneuver produced a reduction in temperature in the risk region of the treated group such that myocardial temperature was reduced an average of 10 degrees C between 30 and 60 min of coronary artery occlusion. Myocardial temperature in the control group remained within 0.3 degree C of baseline during coronary artery occlusion and into reperfusion. Core temperatures were similar in both groups. Hemodynamic parameters and collateral blood flow during occlusion were also equivalent in both groups. After 120 min of coronary occlusion, necrosis in the control group comprised 72 +/- 3% of the ischemic risk region. However, in cooled hearts, infarct size, expressed as a fraction of the risk region was significantly lower. Infarct size in this group averaged 59 +/- 3% of the risk region (p < 0.004 vs. controls), and thus cooling resulted in a salvage of approximately 18% of the risk region.
These results show that reducing myocardial temperature protects ischemic myocardium during a long duration of ischemia even if initiated after coronary artery occlusion.
先前我们观察到，在30分钟冠状动脉闭塞发作之前或之后不久，通过冷却心脏的风险区域可使梗死面积大幅减小。虽然这是梗死兔模型中使用的标准缺血持续时间，但它可能无法反映晚期再灌注患者的情况。长时间缺血时局部低温的影响以及干预措施较晚应用时的影响尚不清楚。本研究检验了这样一个假设，即即使在冠状动脉闭塞后很久才开始，局部降低心脏温度也能在长时间缺血（2小时）期间保护心肌。
对麻醉的兔子进行2小时冠状动脉闭塞和3小时再灌注。兔子被随机分为治疗组：冠状动脉闭塞30分钟后开始局部心肌冷却（n = 14），或对照组，不进行干预（n = 12）。测量风险区域的心肌温度、血流动力学和局部心肌血流量。
闭塞后30分钟时，两组缺血区温度相似，但冷却操作使治疗组风险区域温度降低，冠状动脉闭塞30至60分钟期间心肌温度平均降低10摄氏度。对照组心肌温度在冠状动脉闭塞期间及再灌注期间保持在基线的0.3摄氏度以内。两组的核心温度相似。闭塞期间的血流动力学参数和侧支血流量在两组中也相当。冠状动脉闭塞120分钟后，对照组坏死面积占缺血风险区域的72±3%。然而，在冷却的心脏中，梗死面积（以风险区域的比例表示）显著降低。该组梗死面积平均为风险区域的59±3%（与对照组相比，p < 0.004），因此冷却使约18%的风险区域得以挽救。
这些结果表明，降低心肌温度可在长时间缺血期间保护缺血心肌，即使在冠状动脉闭塞后开始降温也是如此。
