Cardioprotective effect of therapeutic hypothermia at 34°C against ischaemia/reperfusion injury mediated by PI3K and nitric oxide in a rat isolated heart model

Toshiaki Mochizuki, Shuchun Yu, Takasumi Katoh, Katsunori Aoki, Shigehito Sato

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Aim: Therapeutic hypothermia (TH) is widely used as a cardioprotective treatment for cardiac arrest. TH at 30-32°C during ischaemia and reperfusion has a cardioprotective effect. The aims of the study were to examine whether TH at 34°C with late induction (immediately after the start of reperfusion) has a cardioprotective effect and to determine if this effect is mediated by nitric oxide (NO) and phosphatidylinositol 3'-kinase (PI3K). Methods: Langendorff perfusion of Sprague-Dawley rat hearts was initiated at 75. mmHg at 37°C. Left ventricle infarct sizes were evaluated by triphenyltetrazolium chloride staining after Langendorff perfusion in 6 groups (each n=7): control group; ischaemia group, with 34°C TH during ischaemia for 30. min and reperfusion for 180. min; reperfusion group, with 34°C TH induced solely during the reperfusion period; the l-NAME (NO synthase inhibitor), LY294002, and wortmannin (PI3K inhibitors) groups, which were treated similarly to the reperfusion group with the addition of each compound. Results: TH reduced the left ventricle infarct size from 54.2 ± 14.8% of the control group to 11.9 ± 6.3% (ischaemia group, p<0.001) and to 23.5 ± 10.5% (reperfusion group, p<0.001). l-NAME, LY294002, and wortmannin reversed the cardioprotective effect of TH induced during reperfusion to 42.5 ± 10.6% (p=0.009), 40.9 ± 4.1% (p=0.021), and 51.9 ± 13.0% (p<0.001), respectively. Circulatory temperatures reached 34°C within 5. min in all groups subjected to TH. Conclusions: TH of 34°C showed a cardioprotective effect even with late initiation of cooling during reperfusion. The effect was mediated by NO and PI3K.

Original languageEnglish
Pages (from-to)238-242
Number of pages5
JournalResuscitation
Volume83
Issue number2
DOIs
Publication statusPublished - 02-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Emergency
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Cardioprotective effect of therapeutic hypothermia at 34°C against ischaemia/reperfusion injury mediated by PI3K and nitric oxide in a rat isolated heart model'. Together they form a unique fingerprint.

Cite this