Abstract
OBJECTIVE: Vasoplegia and endothelial dysfunction are well-known complications of cardioplegia and cardiopulmonary bypass (CP/CPB). Our lab has previously shown that endothelial adherens junction impairment is driven by vascular endothelial (VE)-cadherin phosphorylation. In this study we investigate the interplay of hypertension and CP/CPB. METHODS: Right atrial tissue was harvested pre- and post-CP/CPB from patients undergoing surgery. Patients were stratified into nonhypertensive, controlled hypertension, and uncontrolled hypertension groups based on history and in-office blood pressure measurements. Atrial tissue was sent for transcriptomics. Expression, phosphorylation, and localization of VE-cadherin was assessed by immunoblotting and immunohistochemistry. Atrial microvascular reactivity to adenosine diphosphate was assessed by videomicroscopy. RESULTS: Several genes related to reactive oxygen species handling, nitric oxide signaling, and adherens junctions were suppressed in patients with uncontrolled hypertension versus nonhypertensive patients pre-CP/CPB. By immunoblotting, patients with uncontrolled hypertension had significantly higher levels of phosphorylated VE-cadherin (p-VE cadherin) and higher ratios of p-VE cadherin/VE-cadherin compared with nonhypertensive (P < .05). Perivascular p-VE cadherin density by immunofluorescence was higher in patients with uncontrolled hypertension compared with nonhypertensive patients and patients with controlled hypertension (P < .05). There were significant decreases in vasodilatory response to adenosine diphosphate after CP/CPB (P < .05) in patients with uncontrolled hypertension compared with nonhypertensive patients. Patients with uncontrolled hypertension had significantly higher increases in weight on postoperative day 1 compared with nonhypertensive patients (P < .05). CONCLUSIONS: Our study supports a 2-hit model in which hypertension primes the endothelium for dysfunction, and CP/CPB amplifies this injury through impaired reactive oxygen species handling, nitric oxide dysregulation, and adherens junction destabilization. These findings highlight the importance of preoperative hypertension management to improve postoperative outcomes.