Mild hypothermia reduces infarct size in the beating rabbit heart: a practical intervention for acute myocardial infarction?

The present study describes a method for rapidly cooling the whole body via its blood pool and tests whether cooling instituted after ischemia has begun can still limit infarction. We also evaluated whether the cardiac protection seen with cooling could be added to that from ischemic preconditioning. Recently it was reported that lowering myocardial temperature by only several degrees greatly slows the extent of myocardial infarction in the beating heart experiencing regional ischemia. To further explore the potential of hypothermia for myocardial protection, rabbits underwent either a 30-, 45- or 60-min coronary artery occlusion and 3-h reperfusion. Blood from a carotid artery was allowed to circulate through a heat exchanger immersed in ice water and return to a jugular vein until the blood temperature in the left atrium reached the target temperature of 35 or 32 degrees C. Furthermore, to elucidate the mechanism of hypothermia's protection, we also examined its effect on isolated cardiomyocytes. Rewarming began upon reperfusion in all protocols. Cooling to 32 degrees C before a 30-min ischemia reduced infarct size from 37.3 +/- 2.5% (n = 6) of the risk zone in normothermic controls to 3.6 +/- 0.3% (n = 6). When cooling was begun 10 or 20 min after the onset of ischemia infarct size was still significantly smaller [8.1 +/- 1.2% and 22.8 +/- 1.8%, respectively (n = 6 in each group)]. Less but significant protection was also seen with cooling to 35 degrees C. Cooling caused only mild bradycardia and hypotension and no apparent arrhythmias. Forty-five min of regional ischemia caused 50.7 +/- 3.3% (n = 6) of risk zone to infarct in untreated hearts. Preconditioning with 5-min ischemia/10-min reperfusion reduced infarct size to 27.5 +/- 2.5% (n = 6). Cooling to 32 degrees C starting 20 min after the onset of ischemia protected the heart (28.7 +/- 2.6% infarction, n = 8), and this protection could be added to the effect from ischemic preconditioning (6.3 +/- 2.3% infarction, n = 6). In the myocyte model, hypothermia and ischemic preconditioning delayed the progressive increase in osmotic fragility that occurs during simulated ischemia in an additive way, but only hypothermia delayed the appearance of contracture suggesting that different mechanisms are involved. Hence blood pool cooling was easily induced and well tolerated and protected the beating heart against infarction even when hypothermia was started after the onset of coronary occlusion. We conclude that hypothermia might be a simple and useful therapy for patients presenting with acute myocardial infarction.