Adenosine Triphosphate - Sensitive Potassium Channel Opener Diazoxide Reduces Myocardial Stunning in a Porcine Lad Occlusion Model

Introduction: Adenosine triphosphate - sensitive potassium (K ATP ) channels provide endogenous myocardial protection by coupling cell membrane potential to metabolism, as they are inhibited by ATP and open during times of metabolic stress. Pharmacologic opening of K ATP channels mimics ischemic preconditioning, and diazoxide (DZX) preserves myocardial function following prolonged global ischemia. Hypothesis: We hypothesized that DZX would reduce myocardial stunning after left anterior descending coronary artery (LAD) occlusion followed by global ischemia, similar to a clinical situation of acute myocardial infarction followed by coronary revascularization. Methods: Twelve swine underwent LAD occlusion (30 min), followed by 120 min global ischemia protected with hyperkalemic cardioplegia (CPG) +/- DZX (N=6 each), followed by intermittent CPG (q 20 min), then 60 min reperfusion (RF). Cardiac output (CO), mean time to wean from cardiopulmonary bypass (CPB), left ventricular ejection fraction (LVEF), left ventricular developed pressure (LVDP), caspase - 3 (apoptosis), and infarct size were compared. Results: All 6 animals in the DZX group separated from CPB by 30 min RF whereas only 1 and 4 animals in the CPG group had separated at 15 and 30 min, respectively (Figure). DZX was associated with shorter average time to wean from CPB (17.5 vs 27.0 min, p=0.13) and higher CO at all time points during reperfusion (2.9 vs 1.5 L/min at 30 min RF, p=0.05), however, these were not significantly different. DZX was associated with higher LVEF after 30 minutes of reperfusion (42.5 vs 15.8%, p=0.009; Figure). There were no differences between groups in vasopressor use, infarct size, caspase - 3, or LVDP. Conclusions: DZX reduces myocardial stunning and facilitates separation from CPB following LAD occlusion and subsequent global ischemia in a porcine model. The addition of DZX to hyperkalemic cardioplegia has the potential to reduce myocardial stunning in the clinical setting.