Abstract 1557: Calcium Activated Potassium Channels Contribute to Human Coronary Microvascular Dysfunction after Cardioplegia Arrest
Background: Cardioplegic arrest (CP) followed by reperfusion after cardiopulmonary bypass (CPB) induces coronary microvascular dysfunction. We investigated the role of calcium-activated potassium (KCa) channel activation in this dysfunction in the human coronary microvasculature.
Methods: Human atrial tissue was harvested before CP from a nonischemic segment and after CP from an atrial segment exposed to hyperkalemic cold blood-CP (mean CP time: 60-min) followed by 10 min reperfusion. In vitro relaxation responses of pre-contracted arterioles (80–150 μm in diameter) in a pressurized no-flow state were examined in the presence of the following vasodilators: the small and intermediate conductance KCa channel activator NS309 (SK/IK activator); the large conductance KCa channel activator NS1619 (BK activator); the endothelium-independent vasodilator sodium nitroprusside (SNP); and the endothelium-dependent vasodilator substance P.
Results: Post-CP-Reperfusion responses to NS309 (10−5M) and substance P (10−8M) were significantly reduced compared to pre-CP responses (p<0.05), whereas the responses to NS1619 (10−5M) and SNP (10−4M) were unchanged pre- and post-CP-reperfusion. Endothelium denudation significantly diminished NS309-induced vasodilatation and abolished substance P-induced relaxation (p<0.05, respectively), but had no effect on relaxation induced by either NS1619 or SNP.
Conclusion: Cardioplegic arrest followed by reperfusion after CPB causes microvascular dysfunction likely due in part to impaired function of SK and IK channels in the coronary microcirculation. These results may provide novel mechanisms by which to explain endothelial and smooth muscle microvascular dysfunction after cardiac surgery.