Background. Hyperkalemic cardioplegia (Plegisol) has been shown to result in myocyte swelling and reduced contractility. We have demonstrated the elimination of these detrimental effects by the addition of an adenosine triphosphate-sensitive K- (KATP) channel opener. To examine whether the mitochondrial or sarcolemmal KATP channel might be involved, volume and contractility in isolated myocytes from wild-type mice and mice lacking the sarcolemmal KATP channel (Kir6.2-/-) were evaluated. Methods. Myocytes were perfused for 20 minutes each with control 37°C Tyrode's solution, test solution, and then control solution. Test solutions were (n = 10 per group) either 9°C Plegisol or 9°C Plegisol with 100 μmol/L of diazoxide, a putative mitochondrial-specific K ATP channel opener. Cell volume and contractility were measured by digital video microscopy at baseline and during the test solution and reexposure periods. Results. Myocytes from wild-type mice, perfused with 9°C Plegisol, demonstrated significant cell swelling (11.2% ± 0.4%; p < 0.01) and diminished contractility (32.5% ± 9.6% reduction in percent shortening, 47.2% ± 10.1% reduction in peak velocity of shortening, and 52.0% ± 8.8% reduction in peak velocity of relengthening; p < 0.05) versus baseline. Cell swelling and diminished contractility were significantly reduced by the addition of diazoxide. In Kir6.2-/- myocytes, Plegisol caused a greatly reduced level of cell swelling (3.2% ± 0.1%; p < 0.01), and this was unaffected by diazoxide. Contractility was unchanged in Kir6.2-/- myocytes after Plegisol. Conclusions. The sarcolemmal KATP channel appears necessary for exaggerated cell swelling and reduced contractility to occur after hyperkalemic cardioplegia in mouse myocytes.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine