Intestinal ischemia induces late preconditioning against myocardial infarction: a role for inducible nitric oxide synthase

Objective: We tested the hypothesis that occlusion of the superior mesenter ic artery induces late preconditioning against myocardial infarction and ex amined the effects of pharmacological modifiers of inducible nitric oxide s ynthase activity on the late preconditioning in anesthetized rats. Methods: Rats underwent an intestinal ischemia preconditioning protocol (30 min occ lusion of the superior mesenteric artery) or were sham-operated. They were subjected to a sustained 30 min of coronary occlusion and 180 min of reperf usion 24 h later. Results: In rats receiving no pharmacological interventio n, the percentage of myocardial infarct within the area at risk and left ve ntricle was 72+/-4% and 31+/-2%, respectively, in sham-operated rats, and t hese were significantly reduced to 44+/-4% and 23+/-2% (P<0.01) 24 h after intestinal ischemia preconditioning. Myeloperoxidase activity was significa ntly reduced by intestinal ischemia preconditioning. Administration of amin oguanidine (300 mg/kg, s.c.) or S-methylisothiourea sulfate (3 mg/kg, i.v.) , both relative inducible NO synthase inhibitors, 60 or 30 min before susta ined myocardial ischemia not only abolished the late preconditioning afford ed by intestinal ischemia, but also inhibited the ability of intestinal isc hemia preconditioning to significantly reduce neutrophil infiltration. A ch ange in inducible NO synthase activity was not observed in normal myocardiu m 24 h after intestinal ischemia, but 30 min of coronary occlusion signific antly increased the inducible NO synthase activity in the preconditioned gr oup, which was abolished by aminoguanidine or S-methylisothiourea sulfate. Conclusions: These data provide pharmacological evidence that induction of inducible nitric oxide synthase, following intestinal ischemia, is associat ed with increased myocardial tolerance to infarction 24 h later. (C) 2001 E lsevier Science BN. All rights reserved.