Hyperkalemic cardioplegia-induced myocyte swelling and contractile dysfunction: Prevention by diazoxide

Background. Hyperkalemic cardioplegia (9°C) results in significant myocyte swelling and reduced contractility, representing a possible mechanism of myocardial stunning. Adenosine triphosphate-sensitive potassium channel (K _ATP) openers have been shown to ameliorate stunning. This study evaluated the hypothesis that a K_ATP opener would prevent hyperkalemic cardioplegia-induced myocyte swelling and reduced contractility. Methods. Isolated rabbit myocytes were perfused with 37°C Tyrode's solution for 20 minutes, followed by test solution (9°C or 37°C) including control Tyrode's, Tyrode's + 100 μmol/L diazoxide (K_ATP opener), St. Thomas's solution; or 9°C St. Thomas's + 100 μmol/L diazoxide or St. Thomas's + 100 μmol/L diazoxide + 20 μmol/L HMR1098 or 50 μmol/L 5-hydroxydeconoate (K_ATP blockers) for 20 minutes (n = 8 per group). Myocytes were then reexposed to 37°C Tyrode's solution for 20 minutes. Volume and contractility were measured by videomicroscopy and video-based edge detection, respectively. Results. St. Thomas's solution (9°C) caused significant myocyte swelling and associated reduced contractility (p < 0.05). The addition of diazoxide abolished myocyte swelling (p < 0.0001), and eliminated the associated reduced contractility (p < 0.05). Findings were unchanged by the addition of HMR 1098 and 5-hydroxydeconoate. Conclusions. Diazoxide prevented myocyte swelling and reduced contractility secondary to hyperkalemic cardioplegia, and this was unchanged by the addition of either K_ATP channel blocker. Prevention of myocyte swelling was associated with improved contractility, consistent with the hypothesis that myocyte swelling may be a mechanism of myocardial stunning. Diazoxide may play a role in myocyte volume homeostasis by means of a mechanism separate from opening the K_ATP channel.