Cardioprotective Benefits of Adenosine Triphosphate-Sensitive Potassium Channel Opener Diazoxide Are Lost with Administration after the Onset of Stress in Mouse and Human Myocytes - 19/09/14
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Abstract |
Background |
Adenosine triphosphate-sensitive (KATP) potassium channel opener diazoxide (DZX) maintains myocyte volume and contractility during stress via an unknown mechanism when administered at the onset of stress. This study was performed to investigate the cardioprotective potential of DZX when added after the onset of the stresses of hyperkalemic cardioplegia, metabolic inhibition, and hypo-osmotic stress.
Study Design |
Isolated mouse ventricular and human atrial myocytes were exposed to control Tyrode's solution (TYR) for 10 to 20 minutes, test solution for 30 minutes (hypothermic hyperkalemic cardioplegia [CPG], CPG + 100uM diazoxide [CPG+DZX], metabolic inhibition [MI], MI+DZX, mild hypo-osmotic stress [0.9T], or 0.9T + DZX), with DZX added after 10 or 20 minutes of stress, followed by 20 minutes of re-exposure to TYR (±DZX). Myocyte volume (human + mouse) and contractility (mouse) were compared.
Results |
Mouse and human myocytes demonstrated significant swelling during exposure to CPG, MI, and hypo-osmotic stress that was not prevented by DZX when administered either at 10 or 20 minutes after the onset of stress. Contractility after the stress of CPG in mouse myocytes significantly declined when DZX was administered 20 minutes after the onset of stress (p < 0.05 vs TYR). Contractility after hypo-osmotic stress in mouse myocytes was not altered by the addition of DZX.
Conclusions |
To maintain myocyte volume homeostasis and contractility during stress (hyperkalemic cardioplegia, metabolic inhibition, and hypo-osmotic stress), KATP channel opener diazoxide requires administration at the onset of stress in this isolated myocyte model. These data have potential implications for any future clinical application of diazoxide.
Le texte complet de cet article est disponible en PDF.Abbreviations and Acronyms : CPG, DZX, KATP, MI, TYR
Plan
Disclosure Information: Nothing to disclose. |
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Support: Dr Lawton was supported by NIH RO1 HL098182-01A1, NIH 5T32HL007776 (MBJ), and the Barnes Jewish Hospital Foundation. |
Vol 219 - N° 4
P. 803-813 - octobre 2014 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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