Abstract 12589: Delayed Therapeutic Hypothermia Protects Against the Myocardial No-reflow Phenomenon Independent of Infarct Size in a Rat Ischemia/reperfusion Model

Abstract

Background: Adjunctive therapy in addition to reperfusion to reduce myocardial infarct size has been disappointing based on clinical trials. New therapeutic targets independent of infarct size modification are needed. No-reflow predicts poor clinical outcome. In this study, we investigate the effects of a single application of delayed (post-reperfusion) therapeutic hypothermia (TH) on no-reflow in rats. Methods: Rats were subjected to 60 min of coronary artery occlusion followed by 3 hours of reperfusion. Rats were divided into normothermic (n=5) and TH (n=5) groups. In the TH, hypothermia was initiated at 1 minute after coronary artery reperfusion by pumping room-temperature (22 °C) saline into and out of the thoracic cavity for 1 hour. This decreased intra-thoracic temperature to around 27 °C within a few minutes. At 3 hours after reperfusion, hearts were excised for infarct size (tetrazolium staining) and no-reflow zone (Thioflavin S technique) measurement. Results: Ischemic risk area (expressed as % of LV area, assessed by blue dye technique) was 52.4 ± 2.9% in normothermic group and 44.8±3.7% in TH group (p=0.15). Infarct size (expressed as % of risk area) was similar between normothermic (73.8 ±3.8% ) and TH (72.0± 4.0%, p = 0.76) groups. No-reflow area (expressed as % of risk area) was significantly reduced in TH group (18.0 ± 4.4%) compared with normothermic group (39.5 ± 2.9%, P = 0.005). When expressed as % of necrotic area, no-reflow area was reduced by more than half in TH group (25.5 ± 6.4%) versus in normothermic group (54.4 ± 5.3%, P = 0.01). Conclusions: A single delayed TH markedly diminishes reperfusion induced microvascular damage and no-reflow even when initiated after reperfusion, and independent of infarct size.