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Optimal timing of hypothermia in relation to myocardial reperfusion

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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.

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Abbreviations

AAR:

Area at risk

ECG:

Electrocardiography

IS:

Infarct size

SPECT:

Single photon emission computed tomography

MRI:

Magnetic resonance imaging

LAD:

Left anterior descending coronary artery

PCI:

Percutaneous coronary intervention

MO:

Microvascular obstruction

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Acknowledgments

We would like to thank Boston Scientific Cardiology, Nordic AB (Helsingborg, Sweden) for their generosity in unrestricted donations of catheters and guide wires for use in animal research and Philips Innercool therapies Inc, San Diego, CA, USA for an unrestricted loan of the Celsius Control™ cooling console. This work was supported by the Swedish Research Council (VR 521-2009-2276), the Swedish Heart and Lung Foundation and the Vascular Wall program (Lund University Faculty of Medicine). David Erlinge is a holder of the Lars Werkö distinguished research fellowship from the Swedish Heart and Lung Foundation.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Coronary Heart Disease, Skane University Hospital, Lund University, 221 85, Lund, Sweden

    Matthias Götberg, Jesper van der Pals, Michael Götberg, Göran K. Olivecrona, Sasha Koul & David Erlinge

  2. Department of Clinical Physiology, Skane University Hospital, Lund University, Lund, Sweden

    Mikael Kanski, Andreas Otto, Henrik Engblom, Martin Ugander & Håkan Arheden

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  1. Matthias Götberg
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  2. Jesper van der Pals
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  3. Michael Götberg
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  4. Göran K. Olivecrona
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Correspondence to David Erlinge.

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Götberg, M., van der Pals, J., Götberg, M. et al. Optimal timing of hypothermia in relation to myocardial reperfusion. Basic Res Cardiol 106, 697–708 (2011). https://doi.org/10.1007/s00395-011-0195-7

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