Serotonin-induced coronary microvessel contractions post cardioplegia, cardiopulmonary bypass are mediated in part via the phospholipase A2 pathway in patients

Abstract

INTRODUCTION: Vasomotor dysfunction after cardiac surgery with cardioplegia and cardiopulmonary bypass (CPB) is estimated to occur in up to 2.5 % of patients, with EKG changes occurring in up to 8%. This dysfunction is thought to be caused by microvascular spasm and leads to myocardial ischemia and worsening cardiac function postoperatively. Phospholipases are involved in signal transduction pathways and regulate many inflammatory pathways. In this study, we examined the role of phospholipases A2 and C in serotonin-induced vasospasm post-CPB. METHODS: Right atrial tissue was harvested from patients undergoing coronary artery bypass grafting (n 5) before initiation of CPB (pre) and after termination of CPB (post). Cold blood cardioplegia was used. We examined coronary arterioles (70- 180 m) for vascular responses to serotonin alone and in the presence of phospholipase A2 (quinacrine, 10-9 to 10-5 mol/L) or phospholipase C inhibitors (U73122, 10-9 to 10-5 mol/L). RESULTS: Microvessels demonstrated a slight relaxation response to serotonin pre-CPB, which shifted to a strong dose-dependent contraction post-CPB. At the highest concentration, serotonin caused a 18.9%2%contraction.Additionofquinacrinesignificantlyinhib