Combined blockade of the Na+ channel and the Na+/H+ exchanger virtually prevents ischemic Na+ overload in rat hearts
- 71 Downloads
Blocking either the Na+ channel or the Na+/H+ exchanger (NHE) has been shown to reduce Na+ and Ca2+ overload during myocardial ischemia and reperfusion, respectively, and to improve post-ischemic contractile recovery. The effect of combined blockade of both Na+ influx routes on ionic homeostasis is unknown and was tested in this study. [Na+]i, pHi and energy-related phosphates were measured using simultaneous 23Na- and 31P-NMR spectroscopy in isolated rat hearts. Eniporide (3 μM) and/or lidocaine (200 μM) were administered during 5 min prior to 40 min of global ischemia and 40 min of drug free reperfusion to block the NHE and the Na+ channel, respectively. Lidocaine reduced the rise in [Na+]i during the first 10 min of ischemia, followed by a rise with a rate similar to the one found in untreated hearts. Eniporide reduced the ischemic Na+ influx during the entire ischemic period. Administration of both drugs resulted in a summation of the effects found in the lidocaine and eniporide groups. Contractile recovery and infarct size were significantly improved in hearts treated with both drugs, although not significantly different from hearts treated with either one of them.
KeywordsNHE Na+ channel NMR spectroscopy ischemia–reperfusion
Unable to display preview. Download preview PDF.
MtH was supported by The Netherlands Heart Foundation (grant 98.141). Equipment was financed by The Netherlands Organization for Scientific Research (NWO, grant 902-16-202), the Royal Netherlands Academy for Arts and Sciences (KNAW, grant D96.695) and the Interuniversity Cardiology Institute of the Netherlands. Eniporide was kindly provided by Merck KGaA (Darmstadt, Germany).
- 4.Schäfer C, Ladilov YV, Schäfer M, Piper HM: Inhibition of NHE protects reoxygenated cardiomyocytes independently of anoxic Ca2+ overload and acidosis. Am J Physiol279:H2143–H2150, 2000Google Scholar
- 17.Ten Hove M, Nederhoff MGJ, Van Echteld CJA: Relative contributions of Na+/H+ exchange and Na+/HCO3− co-transport to ischemic Na+i overload in isolated rat hearts. Am J Physiol288: H287–H292, 2004Google Scholar
- 18.Portman MA, Panos AL, Xiao Y, Anderson DL, Ning X: HOE-642 (cariporide) alters pHi and diastolic function after ischemia during reperfusion in pig hearts in situ. Am J Physiol280: H830–H834, 2001Google Scholar