© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Activity of the Na+/H+ exchanger is critical to reperfusion damage and preconditioning in the isolated rat heart
Institute of Biomedical Research and Department of Physiology, University of Sydney, F13, Sydney, NSW 2006, Australia
* Corresponding author. Tel.: +61-2-9351-4602; fax: +61-2-9351-2058 david.allen{at}physiol.usyd.edu.au
Objective: Removal of protons from the heart during ischemia and/or reperfusion by the cardiac Na+/H+ exchanger (NHE1) leads to Na+ entry; this causes Ca2+ influx and is thought to contribute to ischemic and/or reperfusion damage. The extent to which Na+ enters during ischemia as opposed to reperfusion is disputed and has important implications for the therapeutic use of NHE1 inhibitors as protection against ischemic damage. Preconditioning has recently been proposed to inhibit NHE1 during reperfusion. The objective of the present study was to determine the activity of NHE1 during ischemia, reperfusion and following preconditioning. Methods: The experiments were on isolated perfused rat hearts in which left ventricular developed pressure (LVDP) and intracellular sodium and pH were measured. Results: LVDP following 30 min of ischemia recovered to 14±3% of pre-ischemic level. Application of the NHE1 inhibitor HOE 642 during ischemia and reperfusion improved recovery of LVDP to 77±9%. When HOE was applied at the moment of reperfusion the recovery of LVDP was reduced to 54±6%. To overcome possible delays in the delivery of HOE, the drug was applied at 28 min of ischemia; under these conditions recovery of LVDP (71±7%) was not significantly different to HOE throughout ischemia and reperfusion. HOE had no effect on the recovery of preconditioned hearts. NHE1 activity was assessed by the [Na+]i and pHi changes in response to brief exposure to Na+ lactate (NaL). In control hearts, activity of NHE1 caused a pHi recovery of 0.034±0.007 pH units and was associated with a [Na+]i rise of 7.5±0.5 mmol/l. After 5-min reperfusion following ischemia, NaL application caused a pHi recovery (0.046±0.007) and a larger [Na+]i rise (15.8±0.6 mmol/l). After 5-min reperfusion of preconditioned hearts, NaL application caused a smaller recovery pH recovery (0.013±0.002) and a smaller [Na+]i rise (4.2±0.5 mmol/l). Conclusions: These findings suggest that NHE1 is activated in early reperfusion after ischemia but inhibited during early reperfusion in preconditioned hearts. Overall our results point to a critical period of activity of NHE1 in early reperfusion which is inhibited by preconditioning.
KEYWORDS Acidosis; Ischemia; Na/H exchanger; Preconditioning; Reperfusion
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. E. C. van Hoorn, R. J. Nijveldt, P. G. Boelens, Z. Hofman, P. A. M. van Leeuwen, and K. van Norren Effects of Preoperative Flavonoid Supplementation on Different Organ Functions in Rats JPEN J Parenter Enteral Nutr, July 1, 2006; 30(4): 302 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ten Hove and C. J.A Van Echteld Limited effects of post-ischemic NHE blockade on [Na+]i and pHi in rat hearts explain its lack of cardioprotection Cardiovasc Res, February 15, 2004; 61(3): 522 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Stevens, M. Salik Jahania, R. M. Mentzer Jr, and R. D. Lasley Sodium-hydrogen exchange inhibition attenuates in vivo porcine myocardial stunning Ann. Thorac. Surg., February 1, 2004; 77(2): 651 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. F-T Ch'en, E. Dilworth, P. Swietach, R. S Goddard, and R. D Vaughan-Jones Temperature dependence of Na+-H+ exchange, Na+-HCO3- co-transport, intracellular buffering and intracellular pH in guinea-pig ventricular myocytes J. Physiol., November 1, 2003; 552(3): 715 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. YELLON and J. M. DOWNEY Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology Physiol Rev, October 1, 2003; 83(4): 1113 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G Allen and X.-H. Xiao Role of the cardiac Na+/H+ exchanger during ischemia and reperfusion Cardiovasc Res, March 15, 2003; 57(4): 934 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Muraki, C. D. Morris, J. M. Budde, Z.-Q. Zhao, R. A. Guyton, and J. Vinten-Johansen Blood cardioplegia supplementation with the sodium-hydrogen ion exchange inhibitor cariporide to attenuate infarct size and coronary artery endothelial dysfunction after severe regional ischemia in a canine model J. Thorac. Cardiovasc. Surg., January 1, 2003; 125(1): 155 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wu, Y. Soong, G.-M. Zhao, and H. H. Szeto A highly potent peptide analgesic that protects against ischemia-reperfusion-induced myocardial stunning Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H783 - H791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. An, S. G. Varadarajan, A. Camara, Q. Chen, E. Novalija, G. J. Gross, and D. F. Stowe Blocking Na+/H+ exchange reduces [Na+]i and [Ca2+]i load after ischemia and improves function in intact hearts Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2398 - H2409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schulz, M. V Cohen, M. Behrends, J. M Downey, and G. Heusch Signal transduction of ischemic preconditioning Cardiovasc Res, November 1, 2001; 52(2): 181 - 198. [Full Text] [PDF]
|
|
|
|
|
|
M. Avkiran, G. Gross, M. Karmazyn, H. Klein, E. Murphy, and K. Ytrehus Na+/H+ exchange in ischemia, reperfusion and preconditioning Cardiovasc Res, April 1, 2001; 50(1): 162 - 163. [Full Text] [PDF]
|
|
|
|
|
|
D. G Allen and X.-h. Xiao Na+ entry during ischemia, reperfusion and preconditioning Cardiovasc Res, April 1, 2001; 50(1): 164 - 166. [Full Text] [PDF]
|
|
|
|
|
|
J. W.T Fiolet Reperfusion injury and ischemic preconditioning: two sides of a coin? Cardiovasc Res, November 1, 2000; 48(2): 185 - 187. [Full Text] [PDF]
|
|