Mona Soliman1. 1. Department of Physiology, College of Medicine, King Khalid University Hospital, P.O. Box 2925 (29), Riyadh 11461, Saudi Arabia.
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. CONCLUSION: Our results suggest that DMA protects the heart against post-resuscitation myocardial injury.
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. CONCLUSION: Our results suggest that DMA protects the heart against post-resuscitation myocardial injury.
Entities:
Keywords:
Contractility; Dimethyl amiloride; Hemorrhage; Isolated heart; Langendorff; Rat
Authors: H M Piper; C Balser; Y V Ladilov; M Schäfer; B Siegmund; M Ruiz-Meana; D Garcia-Dorado Journal: Basic Res Cardiol Date: 1996 May-Jun Impact factor: 17.165
Authors: G N Pierce; W C Cole; K Liu; H Massaeli; T G Maddaford; Y J Chen; C D McPherson; S Jain; D Sontag Journal: J Pharmacol Exp Ther Date: 1993-06 Impact factor: 4.030