Leukocyte-type 12-lipoxygenase-deficient mice show impaired ischemic preconditioning-induced cardioprotection
American Journal of Physiology. Heart and Circulatory Physiology
cyte-type 12-lipoxygenase-deficient mice show impaired ischemic preconditioning-induced cardioprotection. Am J Physiol Heart Circ Physiol 280: H1963-H1969, 2001.-To investigate the role of 12-lipoxygenase in preconditioning, we examined whether hearts lacking the "leukocyte-type" 12lipoxygenase (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 (Ϯpreconditioning)
... (Ϯpreconditioning) and during global ischemia and reperfusion. Postischemic function (ratepressure 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 Ϯ 12% in preconditioned vs. 44 Ϯ 7% in nonpreconditioned hearts) but not in 12-LOKO hearts (47 Ϯ 7% in preconditioned vs. 33 Ϯ 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 Ϯ 4%) compared with nonpreconditioned hearts (62 Ϯ 10%) but not in 12-LOKO hearts (85 Ϯ 3% in preconditioned vs. 63 Ϯ 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.