Rajesh Dash1, Yoshiaki Mitsutake2, Wook Bum Pyun3, Fady Dawoud4, Jennifer Lyons2, Atsushi Tachibana2, Kazuyuki Yahagi5, Yuka Matsuura2, Frank D Kolodgie5, Renu Virmani5, Michael V McConnell6, Uday Illindala4, Fumiaki Ikeno7, Alan Yeung7. 1. Division of Cardiovascular Medicine, Stanford University, Stanford, California; Cardiovascular Institute, Stanford University, Stanford, California. Electronic address: rhombus@stanford.edu. 2. Division of Cardiovascular Medicine, Stanford University, Stanford, California. 3. Division of Cardiovascular Medicine, Stanford University, Stanford, California; School of Medicine, Ewha Womans University, Seoul, South Korea. 4. ZOLL Circulation, Inc., San Jose, California. 5. CVPath Institute, Inc., Gaithersburg, Maryland. 6. Division of Cardiovascular Medicine, Stanford University, Stanford, California; Cardiovascular Institute, Stanford University, Stanford, California; Department of Electrical Engineering; Stanford University, Stanford, California; Verily Life Sciences, Mountain View, California. 7. Division of Cardiovascular Medicine, Stanford University, Stanford, California; Cardiovascular Institute, Stanford University, Stanford, California.
Abstract
OBJECTIVES: The study investigated whether a dose response exists between myocardial salvage and the depth of therapeutic hypothermia. BACKGROUND: Cardiac protection from mild hypothermia during acute myocardial infarction (AMI) has yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve myocardial salvage. METHODS: Swine (n = 24) undergoing AMI were assigned to 3 reperfusion groups: normothermia (38°C) and mild (35°C) and moderate (32°C) hypothermia. One-hour anterior myocardial ischemia was followed by rapid endovascular cooling to target reperfusion temperature. Cooling began 30 min before reperfusion. Target temperature was reached before reperfusion and was maintained for 60 min. Infarct size (IS) was assessed on day 6 using cardiac magnetic resonance, triphenyl tetrazolium chloride, and histopathology. RESULTS: Triphenyl tetrazolium chloride area at risk (AAR) was equivalent in all groups (p = 0.2), but 32°C exhibited 77% and 91% reductions in IS size per AAR compared with 35°C and 38°C, respectively (AAR: 38°C, 45 ± 12%; 35°C, 17 ± 10%; 32°C, 4 ± 4%; p < 0.001) and comparable reductions per LV mass (LV mass: 38°C, 14 ± 5%; 35°C, 5 ± 3%; 32°C 1 ± 1%; p < 0.001). Importantly, 32°C showed a lower IS AAR (p = 0.013) and increased immunohistochemical granulation tissue versus 35°C, indicating higher tissue salvage. Delayed-enhancement cardiac magnetic resonance IS LV also showed marked reduction at 32°C (38°C: 10 ± 4%, p < 0.001; 35°C: 8 ± 3%; 32°C: 3 ± 2%, p < 0.001). Cardiac output on day 6 was only preserved at 32°C (reduction in cardiac output: 38°C, -29 ± 19%, p = 0.041; 35°C: -17 ± 33%; 32°C: -1 ± 28%, p = 0.041). Using linear regression, the predicted IS reduction was 6.7% (AAR) and 2.1% (LV) per every 1°C reperfusion temperature decrease. CONCLUSIONS: Moderate (32°C) therapeutic hypothermia demonstrated superior and near-complete cardioprotection compared with 35°C and control, warranting further investigation into clinical applications.
OBJECTIVES: The study investigated whether a dose response exists between myocardial salvage and the depth of therapeutic hypothermia. BACKGROUND: Cardiac protection from mild hypothermia during acute myocardial infarction (AMI) has yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve myocardial salvage. METHODS:Swine (n = 24) undergoing AMI were assigned to 3 reperfusion groups: normothermia (38°C) and mild (35°C) and moderate (32°C) hypothermia. One-hour anterior myocardial ischemia was followed by rapid endovascular cooling to target reperfusion temperature. Cooling began 30 min before reperfusion. Target temperature was reached before reperfusion and was maintained for 60 min. Infarct size (IS) was assessed on day 6 using cardiac magnetic resonance, triphenyl tetrazolium chloride, and histopathology. RESULTS:Triphenyl tetrazolium chloride area at risk (AAR) was equivalent in all groups (p = 0.2), but 32°C exhibited 77% and 91% reductions in IS size per AAR compared with 35°C and 38°C, respectively (AAR: 38°C, 45 ± 12%; 35°C, 17 ± 10%; 32°C, 4 ± 4%; p < 0.001) and comparable reductions per LV mass (LV mass: 38°C, 14 ± 5%; 35°C, 5 ± 3%; 32°C 1 ± 1%; p < 0.001). Importantly, 32°C showed a lower IS AAR (p = 0.013) and increased immunohistochemical granulation tissue versus 35°C, indicating higher tissue salvage. Delayed-enhancement cardiac magnetic resonance IS LV also showed marked reduction at 32°C (38°C: 10 ± 4%, p < 0.001; 35°C: 8 ± 3%; 32°C: 3 ± 2%, p < 0.001). Cardiac output on day 6 was only preserved at 32°C (reduction in cardiac output: 38°C, -29 ± 19%, p = 0.041; 35°C: -17 ± 33%; 32°C: -1 ± 28%, p = 0.041). Using linear regression, the predicted IS reduction was 6.7% (AAR) and 2.1% (LV) per every 1°C reperfusion temperature decrease. CONCLUSIONS: Moderate (32°C) therapeutic hypothermia demonstrated superior and near-complete cardioprotection compared with 35°C and control, warranting further investigation into clinical applications.
Authors: Matthias Götberg; Jesper van der Pals; Michael Götberg; Göran K Olivecrona; Mikael Kanski; Sasha Koul; Andreas Otto; Henrik Engblom; Martin Ugander; Håkan Arheden; David Erlinge Journal: Basic Res Cardiol Date: 2011-06-16 Impact factor: 17.165
Authors: Matthias Götberg; Göran K Olivecrona; Sasha Koul; Marcus Carlsson; Henrik Engblom; Martin Ugander; Jesper van der Pals; Lars Algotsson; Håkan Arheden; David Erlinge Journal: Circ Cardiovasc Interv Date: 2010-08-24 Impact factor: 6.546
Authors: Xue-Han Ning; Shi-Han Chen; Cheng-Su Xu; Linheng Li; Lena Y Yao; Kun Qian; Julia J Krueger; Outi M Hyyti; Michael A Portman Journal: J Appl Physiol (1985) Date: 2002-05
Authors: Einar Heiberg; Martin Ugander; Henrik Engblom; Matthias Götberg; Göran K Olivecrona; David Erlinge; Håkan Arheden Journal: Radiology Date: 2007-11-30 Impact factor: 11.105
Authors: Renaud Tissier; Nicolas Couvreur; Bijan Ghaleh; Patrick Bruneval; Fanny Lidouren; Didier Morin; Roland Zini; Alain Bize; Mourad Chenoune; Marie-France Belair; Chantal Mandet; Martine Douheret; Jean-Luc Dubois-Rande; James C Parker; Michael V Cohen; James M Downey; Alain Berdeaux Journal: Cardiovasc Res Date: 2009-02-05 Impact factor: 10.787
Authors: Stefanie Marek-Iannucci; Amandine Thomas; Jean Hou; Annunziata Crupi; Jon Sin; David J Taylor; Lawrence S Czer; Fardad Esmailian; Robert M Mentzer; Allen M Andres; Roberta A Gottlieb Journal: Sci Rep Date: 2019-07-10 Impact factor: 4.379
Authors: Jin Ho Beom; Ju Hee Kim; Jeho Seo; Jung Ho Lee; Yong Eun Chung; Hyun Soo Chung; Sung Phil Chung; Chul Hoon Kim; Je Sung You Journal: PLoS One Date: 2021-01-27 Impact factor: 3.240