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Optimal timing of hypothermia in relation to myocardial reperfusion.

Götberg, Matthias LU ; vanderPals, Jesper LU ; Götberg, Michael; Olivecrona, Göran LU ; Kanski, Mikael; Koul, Sasha LU ; Otto, Andreas; Engblom, Henrik LU ; Ugander, Martin LU and Arheden, Håkan LU , et al. (2011) In Basic research in cardiology 106. p.697-708
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... (More)
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. (Less)
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Basic research in cardiology
volume
106
pages
697 - 708
publisher
Springer
external identifiers
  • WOS:000293533000002
  • PMID:21674301
  • Scopus:80054696595
ISSN
1435-1803
DOI
10.1007/s00395-011-0195-7
language
English
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yes
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977d7a21-82bc-4606-9d2e-9ee35ee86231 (old id 2008049)
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http://www.ncbi.nlm.nih.gov/pubmed/21674301?dopt=Abstract
date added to LUP
2011-07-05 12:06:03
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2016-10-13 04:31:28
@misc{977d7a21-82bc-4606-9d2e-9ee35ee86231,
  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 &lt;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.},
  author       = {Götberg, Matthias and vanderPals, Jesper and Götberg, Michael and Olivecrona, Göran and Kanski, Mikael and Koul, Sasha and Otto, Andreas and Engblom, Henrik and Ugander, Martin and Arheden, Håkan and Erlinge, David},
  issn         = {1435-1803},
  language     = {eng},
  pages        = {697--708},
  publisher    = {ARRAY(0x9960590)},
  series       = {Basic research in cardiology},
  title        = {Optimal timing of hypothermia in relation to myocardial reperfusion.},
  url          = {http://dx.doi.org/10.1007/s00395-011-0195-7},
  volume       = {106},
  year         = {2011},
}