Leukocyte-type 12-lipoxygenase-deficient mice show impaired ischemic preconditioning-induced cardioprotection

Scott A. Gabel, Robert E. London, Colin D. Funk, Charles Steenbergen, Elizabeth Murphy

Research output: Contribution to journalArticle

Abstract

To investigate the role of 12-lipoxygenase in preconditioning, we examined whether hearts lacking the "leukocyte-type" 12-lipoxygenase (12-LOKO) would be protected by preconditioning. In hearts from wild-type (WT) and 12-LOKO mice, left ventricular developed pressure (LVDP) and 31P NMR were monitored during treatment (±preconditioning) and during global ischemia and reperfusion. Postischemic function (rate-pressure product, percentage of initial value) measured after 20 min of ischemia and 40 min of reperfusion was significantly improved by preconditioning in WT hearts (78 ± 12% in preconditioned vs. 44 ± 7% in nonpreconditioned hearts) but not in 12-LOKO hearts (47 ± 7% in preconditioned vs. 33 ± 10% in nonpreconditioned hearts). Postischemic recovery of phosphocreatine was significantly better in WT preconditioned hearts than in 12-LOKO preconditioned hearts. Preconditioning significantly reduced the fall in intracellular pH during sustained ischemia in both WT and 12-LOKO hearts, suggesting that attenuation of the fall in pH during ischemia can be dissociated from preconditioning-induced protection. Necrosis was assessed after 25 min of ischemia and 2 h of reperfusion using 2,3,5-triphenyltetrazolium chloride. In WT hearts, preconditioning significantly reduced the area of necrosis (26 ± 4%) compared with nonpreconditioned hearts (62 ± 10%) but not in 12-LOKO hearts (85 ± 3% in preconditioned vs. 63 ± 11% in nonpreconditioned hearts). Preconditioning resulted in a significant increase in 12(S)-hydroxyeicosatetraenoic acid in WT but not in 12-LOKO hearts. These data demonstrate that 12-lipoxygenase is important in preconditioning.

Original languageEnglish (US)
Pages (from-to)H1963-H1969
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number5 49-5
DOIs
StatePublished - May 2001
Externally publishedYes

Keywords

  • Infarction
  • Myocardial ischemia
  • Nuclear magnetic resonance
  • Prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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