Nitric oxide has no obligatory role in isoflurane late preconditioning against myocardial stunning.

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.

• Authors: Song-Jung Kim, Gautam Malik, Maged M Saad, Sung-Ho Yoon, Joaquin B Gonzalez, George J Crystal
• Journal: Life sciences (Life Sci) Vol. 91 Issue 23-24 Pg. 1201-6 (Dec 10 2012) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 23044225 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Nitroarginine
• Nitric Oxide
• Isoflurane
• Nitric Oxide Synthase Type II

Topics

• Animals
• Blood Flow Velocity
• Blotting, Western
• Dogs
• Ischemic Preconditioning, Myocardial (methods)
• Isoflurane (pharmacology)
• Myocardial Stunning (prevention & control)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Nitroarginine (pharmacology)
• Reperfusion (methods)