title: Inhibition of Na(+)-H(+) exchange before resuscitation following hemorrhagic shock is cardioprotective in rats.
abstract: BACKGROUND
  Stimulation of the Na(+)-H(+) exchanger during resuscitation following hemorrhagic shock results in myocardial injury and dysfunction. Inhibition of the Na(+)-H(+) exchanger appears to be a new pharmacological tool for myocardial protection following ischemia-reperfusion. Our lab showed that inhibition of the Na(+)-H(+) exchanger, using amiloride and dimethyl amiloride, before ex vivo resuscitation of isolated perfused hearts protected the myocardium and improved the post-resuscitation myocardial function. The purpose of the present study was to examine the myocardial protective effects of treating the hemorrhagic shocked rats by intra-arterial injection of 20 μM dimethyl amiloride (DMA), a specific Na(+)-H(+) exchanger blocker, before in vivo resuscitation.
  
  
  METHODS
  Sprague-Dawley rats were assigned to hemorrhagic treated or untreated groups (n = 4 per group). After 60 min of hemorrhagic shock, rats were treated or not by injection of 20 μM 5-(N,N-dimethyl)-amiloride (DMA) intra-arterially. Rats were then resuscitated in vivo and monitored for 30 min. Then hearts were harvested and perfused in the Langendorff system for 60 min for measurements of hemodynamic function.
  
  
  RESULTS
  Administration of DMA before in vivo resuscitation following 60 min of hemorrhagic shock and 30 min of in vivo resuscitation, 20 μM DMA intra-arterially significantly improved post-resuscitation myocardial function.
  
  
  CONCLUSIONS
  Our results suggest that DMA protects the heart against post-resuscitation myocardial injury.
authors: Department of Physiology, College of Medicine, King Khalid University Hospital, P.O. Box 2925 (29), Riyadh 11461, Saudi Arabia.
authors: Mona
authors: M
authors: Soliman
keywords: Contractility; Dimethyl amiloride; Hemorrhage; Isolated heart; Langendorff; Rat
references: Am J Physiol. 1993 Jun;264(6 Pt 2):H1831-5
references: 8391755
references: Shock. 2008 Apr;29(4):519-25
references: 17724433
references: Crit Care. 2004 Oct;8(5):373-81
references: 15469601
references: J Mol Cell Cardiol. 1995 Jan;27(1):53-63
references: 7760373
references: J Pharmacol Exp Ther. 1993 Jun;265(3):1280-91
references: 8510009
references: Am J Physiol. 1990 May;258(5 Pt 2):H1615-9
references: 2337191
references: Basic Res Cardiol. 1996 May-Jun;91(3):191-202
references: 8831938
references: Am J Physiol Cell Physiol. 2008 Nov;295(5):C1454-63
references: 18829897
references: J Pharmacol Exp Ther. 1991 Mar;256(3):1094-100
references: 2005574
references: J Mol Cell Cardiol. 1985 Nov;17(11):1029-42
references: 3001319
references: J Mol Cell Cardiol. 1998 Apr;30(4):829-35
references: 9602432
references: Cardiovasc Res. 1997 Nov;36(2):138-48
references: 9463626