© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Hypothermia during reperfusion limits ‘no-reflow’ injury in a rabbit model of acute myocardial infarction
The Heart Institute of Good Samaritan Hospital, and the University of Southern California, Department of Medicine, Division of Cardiovascular Medicine, Los Angeles, CA 90017, USA
sharon.hale{at}attglobal.net
* Corresponding author. The Heart Institute, Good Samaritan Hospital, 1225 Wilshire Blvd Los Angeles, CA 90017, USA. Tel.: +1-213-977-4045; fax: +1-213-977-4107.
Objective: Reflow following coronary artery occlusion is an important predictor of clinical outcome. This study tests the effects of regional hypothermia, initiated late during ischemia and maintained for 2 h of reperfusion, on the no-reflow phenomenon. Methods: Anesthetized, open-chest New Zealand White rabbits received 30 min of coronary artery occlusion and 3 h reperfusion. Regional myocardial hypothermia (H, n=14), starting 10 min before reperfusion and continuing for 2 h of reperfusion, was compared with normothermia (N, n=14). Regional myocardial blood flow (microspheres) was measured during occlusion and at the end of reperfusion. The anatomic zone of no-reflow (thioflavin S in vivo injection) and infarct size were measured in the ischemic risk region at the end of the study. Results: Myocardial temperature in H rabbits was decreased by 5.0±0.4°C from baseline (37.1±0.2°C) and remained about 32°C during the cooling phase, returning to 36.0±0.3°C at 3 h. N hearts remained within 0.2°C of baseline (37.3±0.1°C) throughout. Both groups were equally ischemic during occlusion, but at the end of reperfusion reflow to the previously ischemic zone was significantly higher in H, 77±5% of normal blood flow versus 36±4% in N (P=0.0001). The zone of anatomic no-reflow was significantly smaller in H, 11±3% of the ischemic risk zone versus 37±3% in N (P=0.0001), and was proportionally smaller when represented as a percent of the necrotic zone 36±6% compared with 75±5% in N. Infarct size, expressed as a percent of the ischemic risk zone was significantly smaller in H vs. N hearts (27±4 and 51±5%, P=0.0000). Conclusion: This study shows that hypothermic therapy initiated late during ischemia and continuing for several hours of reperfusion significantly improves reflow and reduces macroscopic zones of no-reflow and necrosis in this model. The improvement in reflow was greater than would be expected in the H group compared with N, based on the extent of necrosis. As reflow is a predictor of outcome, this intervention may have clinical implications.
KEYWORDS Blood flow; Coronary circulation; Infarction; Ischemia; Regional blood flow
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