title: Optimal timing of hypothermia in relation to myocardial reperfusion.
abstract: 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 38°C was established utilizing an endovascular temperature modulating catheter. The pigs were randomized to a combination hypothermia group (1,000 ml of 4°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 <35°C within 5 min. Combination hypothermia reduced IS/AAR by 18% compared with normothermic controls despite 5 min longer ischemic time (61 ± 5 vs. 74 ± 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.
authors.affiliation: Department of Coronary Heart Disease, Skane University Hospital, Lund University, 221 85 Lund, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Götberg
authors.forename: Jesper
authors.initials: J
authors.lastname: van der Pals
authors.forename: Michael
authors.initials: M
authors.lastname: Götberg
authors.forename: Göran K
authors.initials: GK
authors.lastname: Olivecrona
authors.forename: Mikael
authors.initials: M
authors.lastname: Kanski
authors.forename: Sasha
authors.initials: S
authors.lastname: Koul
authors.forename: Andreas
authors.initials: A
authors.lastname: Otto
authors.forename: Henrik
authors.initials: H
authors.lastname: Engblom
authors.forename: Martin
authors.initials: M
authors.lastname: Ugander
authors.forename: Håkan
authors.initials: H
authors.lastname: Arheden
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007036:Hypothermia, Induced; D008279:Magnetic Resonance Imaging; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon