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Ann Thorac Surg 2003;76:1252-1258
© 2003 The Society of Thoracic Surgeons


Original article: cardiovascular

Intra-myocyte ion homeostasis during ischemia-reperfusion injury: effects of pharmacologic preconditioning and controlled reperfusion

James E. Davies, MDa, Stanley B. Digerness, PhDa, Steven P. Goldberg, MDa, Cheryl R. Killingsworth, PhDa, Charles R. Katholi, PhDb, Paul S. Brookes, PhDc, William L. Holman, MDa*

a Department of Surgery, Birmingham, Alabama, USA
b Department of Medicine, Birmingham, Alabama, USA
c Department of Biostatistics, Birmingham, Alabama, USA, and Department of Pathology, Birmingham, Alabama, USA, University of Alabama at Birmingham, Birmingham, Alabama, USA

Accepted for publication April 8, 2003.

* Address reprint requests to Dr Holman, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
e-mail: wholman{at}its.uab.edu

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 µmol/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 µmol/mL; p = 0.02), but decreased to 19.9 ± 3.2 µmol/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 µmol/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.




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