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  • Title: Nitric oxide has no obligatory role in isoflurane late preconditioning against myocardial stunning.
    Author: Kim SJ, Malik G, Saad MM, Yoon SH, Gonzalez JB, Crystal GJ.
    Journal: Life Sci; 2012 Dec 10; 91(23-24):1201-6. PubMed ID: 23044225.
    Abstract:
    AIMS: Isoflurane has been demonstrated to produce late preconditioning against myocardial stunning. We tested the hypothesis that this effect is dependent upon an increased production of nitric oxide. MAIN METHODS: Studies were performed in 18 conscious dogs, chronically instrumented to measure coronary blood flow and myocardial wall thickening (WT). In Group 1 (control; n=7), a 10-min coronary occlusion was produced followed by reperfusion; WT was monitored until full recovery. In Group 2 (n=6), the same occlusion-reperfusion protocol was performed 24h after inhalation of 1 MAC isoflurane (1.4% in O(2)) for 60 min. In Group 3 (n=5), the late anti-stunning effect of isoflurane was evaluated following non-selective inhibition of NOS with N-nitro-l-arginine (l-NA, 30 mg/kg on 3 days beginning 1 day prior to isoflurane). Expression of eNOS and iNOS protein was measured by Western blotting. KEY FINDINGS: Two to 3h of reperfusion was required for recovery of WT following isoflurane (Group 2). In contrast, without isoflurane (Group 1), WT remained markedly reduced (30% below baseline) at this time point and required more than 6h of reperfusion for recovery. Treatment with l-NA (Group 3) did not alter time-course of recovery of WT following isoflurane. Isoflurane caused an increased expression of eNOS, but not of iNOS. SIGNIFICANCE: Isoflurane produced late preconditioning against myocardial stunning. Although this effect was associated with an up-regulation of eNOS, its persistence following l-NA suggested that an increased production of nitric oxide did not play an obligatory role.
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