Perioperative Angiotensin-(1-7) for Postoperative Cognitive Vulnerability Following Coronary Artery Bypass Surgery: A...

Postoperative cognitive impairment is a common complication following coronary artery bypass grafting (CABG) and is thought to arise from perioperative neurovascular injury, systemic inflammation, and neuroaxonal damage. Despite its clinical impact, there are no approved pharmacologic strategies to mitigate postoperative cognitive vulnerability. Angiotensin-(1-7) (Ang-(1-7); PNA1), a Mas receptor agonist, has demonstrated neurovascular and anti-inflammatory effects in preclinical models, but its perioperative cognitive effects in humans have not been described.

This case series reports outcomes from an incompletely accrued randomized, double-blind, placebo-controlled pilot study in older adults undergoing elective CABG. Five participants (mean age 64.6 years; 80% male) completed all study procedures; three received Ang-(1-7) (200 μg/kg/day subcutaneously) and two received saline as the placebo. Study drug administration was initiated intraoperatively within two hours of chest opening and continued daily for 21 days. Cognitive performance was assessed at baseline and 21 days postoperatively using standardized neuropsychological measures, including face-name associative memory and executive function tasks. Neuroaxonal injury was evaluated using plasma neurofilament light chain (NfL) measured by ultrasensitive single-molecule array assays. Perioperative glucose regulation, blood pressure, renal function, and adverse events were monitored for safety. Participants receiving Ang-(1-7) demonstrated relative preservation of associative memory and attenuation of postoperative NfL levels compared with placebo-treated participants, with no drug-relted adverse events or clinically significant renal or hemodynamic complications observed.

In this small perioperative case series, Ang-(1-7) administration following CABG was feasible and well tolerated and was associated with signals of cognitive preservation and reduced neuroaxonal injury during early postoperative recovery. These findings support further investigation of Ang-(1-7) as a potential perioperative strategy to mitigate postoperative cognitive vulnerability in patients undergoing cardiac surgery.