Effect of Cardioplegia and Cardiopulmonary Bypass on Coronary Microvascular Reactivity

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SUMMARY: Cardiac surgery, especially that involving cardioplegia (CP) and cardiopulmonary bypass (CPB), is associated with significant changes in vasomotor regulation and subsequent organ injury such as neurocognitive deficit, stroke, renal and mesenteric failure, post-operative systemic hypotension and coronary spasm. Hypertension is also associated with severe autonomic dysfunction and vasomotor regulation, as well as with increased morbidity and mortality after surgical procedures. The goal of the proposed research is to determine the effect of well-controlled and poorly controlled hypertension on alterations in vascular signal transduction and function and to investigate the changes that occur in these patients before and after undergoing heart surgery with CP and CPB. Specifically, hypertension-related differences in microvascular function will be investigated with specific focus on 1) myogenic tone, 2) -adrenergic and vasopressin-induced microvascular signaling and contraction, 3) and the differential effects of gender and aging on myogenic, angiotensin I and II, and -adrenergic pathway. These aims will be examined in the microvasculature of well- controlled and poorly controlled hypertensive and age-matched normotensive patients, using in vitro microvascular imaging. This work will be accomplished through an exhaustive approach using molecular and cellular biology techniques to examine gene and protein expression and activation involved in maintaining vascular integrity and signaling following cardiac surgery. The results of these studies may have significant implications regarding the recovery of hypertensive and other patients after cardiac surgery.