Custom Search

News

Friday 01 August 2003

Na+ overload during ischemia and reperfusion in rat hearts: comparison of the Na+/H+ exchange blockers EIPA, cariporide and eniporide.

By: ten Hove M, van Emous JG, van Echteld CJ.

Mol Cell Biochem 2003 Aug;250(1-2):47-54

Intracellular myocardial Na+ overload during ischemia is an important cause of reperfusion injury via reversed Na+/Ca2+ exchange. Prevention of this Na+ overload can be accomplished by blocking the different Na+ influx routes. In this study the effect of ischemic inhibition of the Na+/H+ exchanger (NHE) on [Na+]i, pH, and post-ischemic contractile recovery was tested, using three different NHE-blockers: EIPA, cariporide and eniporide. pHi and [Na+]i were measured using simultaneous 31P and 23Na NMR spectroscopy, respectively, in paced (5 Hz) isolated, Langendorff perfused rat hearts while contractility was assessed by an intraventricular balloon. NHE-blockers (3 microM) were administered during 5 min prior to 30 min of global ischemia followed by 30 min drug-free reperfusion. NHE blockade markedly reduced ischemic Na+ overload; after 30 min of ischemia [Na+]i had increased to 293 +/- 26, 212 +/- 6, 157 +/- 5 and 146 +/- 6% of baseline values in untreated and EIPA (p < 0.01 vs. untreated), cariporide (p < 0.01 vs. untreated) and eniporide (p < 0.01 vs. untreated) treated hearts, respectively. Ischemic acidosis did not differ significantly between groups. During reperfusion, however, recovery of pH, was significantly delayed in treated hearts. The rate pressure product recovered to 12.0 +/- 1.9, 12.1 +/- 2.1, 19.5 +/- 2.8 and 20.4 +/- 2.5 x 10(3) mmHg/min in untreated and EIPA, cariporide (p < 0.01 vs. untreated) and eniporide (p < 0.01 vs. untreated) treated hearts, respectively. In conclusion, blocking the NHE reduced ischemic Na+ overload and improved post-ischemic contractile recovery. EIPA, however, was less effective and exhibited more side effects than cariporide and eniporide in the concentrations used.

Use of this site is subject to the following terms of use