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.

Public Health Relevance

s: Hypertensive patients undergoing cardiac surgery have increased post-operative morbidity and mortality that may be associated with severe vasomotor and autonomic dysfunction leading to organ injury such as neurocognitive dysfunction, stroke, renal and mesenteric failure, systemic hypotension and coronary spasm. We propose to determine the effect of well-controlled and poorly controlled hypertension on alterations in microvascular signal transduction and function that occur in these surgical patients before and after cardiac surgery. We will correlate these changes with changes in neurocognitive function and other clinical outcomes. These studies may have significant implications regarding post-cardiac surgery recovery, especially in patients suffering hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL046716-26A1
Application #
9883231
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Schwartz, Lisa
Project Start
1992-08-01
Project End
2024-03-31
Budget Start
2020-04-15
Budget End
2021-03-31
Support Year
26
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Rhode Island Hospital
Department
Type
DUNS #
075710996
City
Providence
State
RI
Country
United States
Zip Code
02903
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