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

First Author  Gabel SA Year  2001
Journal  Am J Physiol Heart Circ Physiol Volume  280
Issue  5 Pages  H1963-9
PubMed ID  11299195 Mgi Jnum  J:69296
Mgi Id  MGI:1934425 Doi  10.1152/ajpheart.2001.280.5.H1963
Citation  Gabel SA, et al. (2001) Leukocyte-type 12-lipoxygenase-deficient mice show impaired ischemic preconditioning-induced cardioprotection. Am J Physiol Heart Circ Physiol 280(5):H1963-9
abstractText  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 (31)P 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.
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