Optimal timing of hypothermia in relation to myocardial reperfusion
Optimal timing of hypothermia in relation to myocardial reperfusion
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DOI：
10.1007/s00395-011-0195-7
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发表时间：
2011-09-01
影响因子：
9.5
通讯作者：
Erlinge, David
中科院分区：
文献类型：
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作者：
Gotberg, Matthias;van der Pals, Jesper;Erlinge, David
此前两项研究低温作为心肌梗死辅助疗法的临床试验均以失败告终。最近的一项先导性研究表明，脑梗塞面积显著减少。本研究的目的是阐明低温对再灌注损伤的影响，并为未来的临床试验探索最佳的低温方案。将体重40~50 kg的猪麻醉，用血管内调温导管建立38A℃的正常猪温。将猪随机分为亚低温组(1,000毫升4A℃生理盐水加血管内降温，n=8)或常温对照组(n=8)。然后在LAD中充气40分钟(对照组)或45分钟，在最后5分钟内诱导降温。此外，还观察了冷生理盐水诱导的低温(n=8)和再灌注期延长的联合低温(n=7)。再灌流4h后，分别用Gd增强MRI和Tc99-Tetrofosmin SPECT测定梗塞面积和危险面积。联合亚低温组在5分钟内降温至35℃。尽管缺血时间延长了5分钟(61+/-A5vs.74+/-A4%，p=0.03)，但联合低温使IS/AAR比常温对照组降低了18%。冷生理盐水不能降低IS/AAR。在再灌流开始后，将低温治疗延长45分钟并不能带来任何额外的益处。低温治疗的心脏保护作用是由于减轻了缺血和再灌流期间的心肌损伤。结果表明，使用冷盐水输注和血管内降温的低温方案能够在临床环境中诱导低温，而不会延误再灌注治疗。
Two previous clinical trials investigating hypothermia as an adjunct therapy for myocardial infarction have failed. Recently a pilot study has demonstrated a significant reduction in infarct size. The aims of this study were to elucidate the effects of hypothermia on reperfusion injury and to investigate the optimal hypothermia protocol for a future clinical trial. Pigs (40-50 kg) were anesthetized and a normal pig temperature of 38A degrees C was established utilizing an endovascular temperature modulating catheter. The pigs were randomized to a combination hypothermia group (1,000 ml of 4A degrees C saline solution and endovascular cooling, n = 8), or to normothermic controls (n = 8). A PCI balloon was then inflated in the LAD for 40 min (control) or 45 min with hypothermia induced during the last 5 min. Furthermore, hypothermia induced by cold saline alone (n = 8), and prolonged combination hypothermia during reperfusion (n = 7) were also examined. Infarct size and area at risk were determined ex vivo after 4 h of reperfusion using gadolinium-enhanced MRI and Tc-99-tetrofosmin SPECT, respectively. All pigs in the combination hypothermia group were cooled to < 35A degrees C within 5 min. Combination hypothermia reduced IS/AAR by 18% compared with normothermic controls despite 5 min longer ischemic time (61 +/- A 5 vs. 74 +/- A 4%, p = 0.03). Cold saline did not reduce IS/AAR. Prolonging hypothermia treatment after onset of reperfusion by an additional 45 min over that used in a previous paper did not confer any additional benefit. The cardioprotective effects of hypothermia treatment are due to an attenuation of myocardial injury during both ischemia and reperfusion. The results suggest that a hypothermia protocol using a cold saline infusion and endovascular cooling enables hypothermia to be induced in a clinical setting without delaying reperfusion therapy.