Ischemic preconditioning and Na+/H+ exchange inhibition improve reperfusion ion homeostasis.
BACKGROUND
Intramyocyte sodium (Na+) increases during ischemia and reperfusion, which causes myocardial calcium (Ca2+) uptake and leads to myocyte injury or death. This study determines if ischemic preconditioning and myocyte sodium-hydrogen ion (Na+-H+) exchange (NHE) inhibition decreases Na+ gain that otherwise occurs with cardioplegic arrest and reperfusion.


METHODS
Pigs had 1 hour of cardioplegic arrest followed by reperfusion. Group 1 had no intervention (controls). Group 2 received dimethyl amiloride (DMA, an NHE inhibitor), and group 3 had ischemic preconditioning before cardioplegic arrest. Precardioplegia to postreperfusion change in intramyocyte ion content was measured with atomic absorption spectrometry. The time to initial electrical activity and number of defibrillations needed to establish an organized rhythm postreperfusion were used as electrophysiologic variables to measure ischemia-reperfusion injury.


RESULTS
Intramyocyte Na+ content for group 1 increased from 45.9+/-6.7 to 61.9+/-22.5 micromol/g (p = 0.02). Group 2 had an insignificant decrease in intramyocyte Na+ of 27.7+/-19.58 micromol/g (p = 0.06), and group 3 had an insignificant decrease of 10.8+/-46.33 micromol/g (p = 0.48). Interstitial water increased significantly in all groups, but there were no significant increases in intramyocyte water content. Electrophysiologic recovery was similar for all three groups.


CONCLUSIONS
The NHE inhibition and ischemic preconditioning each eliminated the increase in intramyocyte Na+ content that otherwise occurred with cardioplegic arrest and reperfusion in this porcine model. Because their mechanisms are distinct, it is possible that an additive beneficial effect against ischemia-reperfusion injury can be achieved by using NHE inhibition together with a preconditioning stimulus as prereperfusion therapy.
Goldberg
Steven P
SP
Department of Surgery, School of Medicine, University of Alabama at Birmingham, 35294-0007, USA.
Digerness
Stanley B
SB
Skinner
Jonathan L
JL
Killingsworth
Cheryl R
CR
Katholi
Charles R
CR
Holman
William L
WL
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000502:physiology; D013054:Spectrophotometry, Atomic; D013552:Swine
D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D000584:Amiloride; D012964:Sodium