Na(+)-H+ exchange inhibition attenuates ischemic injury in rat random pattern skin flap: the role of mitochondrial ATP-sensitive potassium channels.

Abstract

Necrosis of distal portion of skin flaps due to ischemia still remains a problem in plastic surgery. Following ischemia, a cascade of deleterious events including over-activity of Na(+)-H(+) Exchanger (NHE) takes place. In present study we evaluated the effect of the potent NHE inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA) on ischemic tissue injury in a skin flap model, and investigated the role of mitochondrial ATP-sensitive K(+) channels (K(ATP)) in this phenomenon. Seventy-eight rats were randomly divided into thirteen treatment groups (6 rats each). Four groups received different doses of EIPA in the flap. EIPA/GLY group received an effective dose of a K(ATP) channel blocker, glibenclamide (GLY, 0.3mg/kg) intraperitoneally (i.p.) 30 min before raising the flap, and a local effective dose of EIPA (0.1mM) immediately after raising the flap. EIPA/diazoxide group (EIPA/DIA) received a sub-effective dose of diazoxide (7.5mg/kg i.p.) 30 min before raising the flap and a local sub-effective dose of EIPA (0.075 mM). EIPA 0.1 and 0.2mM significantly increased flap survival area compared to control group (56.01 ± 6.1%, P<0.001). The protective effect of EIPA (0.1mM) was abolished by administration of glibenclamide (0.3mg/kg i.p.). Co-administration of a sub-effective dose of EIPA (0.075 mM), with a sub-effective dose of diazoxide (7.5mg/kg i.p.) significantly improved flap survival (P<0.05). We demonstrated that the NHE inhibitor, EIPA can increase random pattern skin flap survival. Administration of diazoxide potentiates this effect, while glibenclamide abolishes that, implicating that the protective effect of EIPA is mediated through mitochondrial-K(ATP) channels.

• Authors: Hamed Emami, Saman Shafaat Talab, Behtash Ghazi Nezami, Azadeh Elmi, Solmaz Assa, Mohammad Reza Ostovaneh, Ahmad Reza Dehpour
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 698 Issue 1-3 Pg. 330-4 (Jan 05 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 23123348 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• KATP Channels
• Sodium-Hydrogen Exchangers
• Amiloride
• Diazoxide
• Glyburide
• ethylisopropylamiloride

Topics

• Amiloride (analogs & derivatives, pharmacology, therapeutic use)
• Animals
• Dermatologic Surgical Procedures (adverse effects)
• Diazoxide (pharmacology)
• Glyburide (pharmacology)
• Ion Channel Gating (drug effects)
• Ischemia (drug therapy, metabolism, pathology)
• KATP Channels (metabolism)
• Male
• Mitochondria (drug effects, metabolism)
• Postoperative Complications (drug therapy, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)
• Surgical Flaps (pathology)
• Tissue Survival (drug effects)