Abstract
We previously demonstrated that myocyte swelling and reduced contractility secondary to hyperkalemic cardioplegia and hyposmotic stress are attenuated by the addition of diazoxide, an adenosine triphosphate-sensitive potassium channel (K(ATP)) opener. The goal of this study was to investigate the effect of diazoxide on myocyte swelling and reduced contractility after metabolic inhibition and to attempt to summarize the potential mechanisms involved. Isolated rabbit myocytes were perfused with Tyrode's control solution for 20 minutes, followed by test solution for 20 minutes. Test solutions included (1) Tyrode's control, (2) a metabolic inhibition solution containing sodium cyanide and 2-deoxyglucose, (3) metabolic inhibition plus diazoxide, (4) metabolic inhibition plus diazoxide plus HMR1098 (a sarcolemmal K(ATP)-channel blocker), or (5) metabolic inhibition plus diazoxide plus 5-hydroxydeconoate (a mitochondrial K(ATP)-channel blocker). Myocytes were then reexposed to Tyrode's solution for 20 minutes. Volume measurements were taken every 5 minutes. Contractility was recorded using edge-detection software at baseline and at 10 and 20 minutes of reexposure to Tyrode's solution. Simulated ischemia (metabolic inhibition) caused significant myocyte swelling and associated reduced contractility. The addition of diazoxide abolished myocyte swelling and attenuated the associated reduced contractility. Observations with diazoxide were unchanged by the addition of HMR 1098 or 5-hydroxydeconoate. Diazoxide, with or without either K(ATP)-channel blocker, attenuated the significant myocyte swelling and reduced contractility secondary to metabolic inhibition. These data suggest a role for diazoxide, independent of the K(ATP) channel, in myocyte volume homeostasis. In addition, the prevention of myocyte swelling resulted in improved contractility, consistent with previous data and the hypothesis that myocyte swelling may participate in the phenomenon of myocardial stunning.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
