Intra-myocyte ion homeostasis during ischemia-reperfusion injury: effects of pharmacologic preconditioning and controlled reperfusion.
BACKGROUND
This study determines whether controlled reperfusion or diazoxide improves intramyocyte Na(+) homeostasis using a porcine model of severe ischemia-reperfusion injury.


METHODS
Three groups (n = 10 pigs per group) had 75 minutes of left anterior descending artery occlusion during bypass. Group 1 had no treatment (control group), group 2 had controlled reperfusion (500 mL warm cardioplegia) (controlled reperfusion group), and group 3 had diazoxide (50 micromol/L before left anterior descending artery occlusion) (diazoxide group). Biopsies were taken from the left anterior descending artery region before ischemia and at 3, 5, and 10 minutes postreperfusion. Intra-myocyte Na(+) and water contents were determined using atomic absorption spectroscopy, and Na(+) concentrations were calculated.


RESULTS
Intra-myocyte Na(+) increased for the diazoxide group pigs at 3-minutes postreperfusion (21.9 +/- 2.9 vs 34.0 +/- 3.4 micromol/mL; p = 0.02), but decreased to 19.9 +/- 3.2 micromol/mL at 10 minutes postreperfusion (p = 1.0 vs baseline). At 10 minutes postreperfusion, intra-myocyte Na(+) in the controlled reperfusion group was lower than baseline (22.3 +/- 2.7 vs 17.2 +/- 3.1 micromol/mL; p < 0.001). Intra-myocyte Na(+) at 10 minutes postreperfusion for the diazoxide and controlled reperfusion groups was lower than for the control group (p < 0.05).


CONCLUSIONS
Diazoxide and controlled reperfusion improved intra-myocyte Na(+) homeostasis after severe ischemia-reperfusion injury.
Davies
James E
JE
Department of Surgery, Birmingham, University of Alabama at Birmingham, 35294, USA.
Digerness
Stanley B
SB
Goldberg
Steven P
SP
Killingsworth
Cheryl R
CR
Katholi
Charles R
CR
Brookes
Paul S
PS
Holman
William L
WL
D000818:Animals; D003981:Diazoxide / Q000494:pharmacology*; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D015425:Myocardial Reperfusion / Q000379:methods*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013552:Swine; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
D012964:Sodium; D003981:Diazoxide