Poorly Controlled Hypertension Alters Coronary Microvascular Contractile Response to Endothelin‐1 Before and After Cardiac Surgery

Background Patients with chronic hypertension have worse outcomes following on‐pump (cardioplegia and cardiopulmonary bypass [CP/CPB]) cardiac surgery. Altered vasomotor function of the coronary microvasculature to ET‐1 (endothelin‐1) and other agonists may underlie these differences. Methods Heart samples were collected from 85 patients undergoing CP/CPB enrolled in this observational study. Ex vivo coronary microvascular responses to ET‐1, adenosine diphosphate, and sodium nitroprusside were assessed using video microscopy. Immunoblotting, immunohistochemistry, enzyme‐linked immunosorbent assay, and multiomics approaches were also used. Results Coronary microvascular contractile response to ET‐1 in patients with uncontrolled hypertension was increased compared with the other 2 cohorts pre‐ and post‐CP/CPB ( P <0.05 across ET‐1 10 −10 to 10 −7 mmol/L). Adenosine diphosphate‐induced coronary microvascular vasodilation was conversely decreased ( P <0.05 for adenosine diphosphate 10 −5 and 10 −4 mmol/L). Post‐CP/CPB microvascular responses to ET‐1 and adenosine diphosphate were blunted overall ( P <0.05). Antagonism of pro‐vasoconstrictive endothelin A receptor diminished contractile response ( P <0.05). Transcriptomics and proteomics showed wide regulation of pro‐vasoconstrictive pathways. Regression showed that hypertension status and cardiac mass reliably approximated ET‐1‐induced coronary microvascular contraction (R 2 0.95 pre‐CP/CPB, R 2 0.86 post‐CP/CPB), which, in turn, estimated change in ejection fraction pre‐ and post‐CP/CPB ( P <0.05). Patients with uncontrolled hypertension had −11% change in EF when compared with the other 2 groups pooled ( P <0.05). Conclusions Altered coronary microvascular vasomotor function in patients with uncontrolled hypertension may jeopardize myocardial perfusion. Hypertension status and cardiac mass may be used to prognosticate this physiology, which, in turn, estimates change in ejection fraction postoperatively. Perioperative endothelin receptor blockers may benefit patients with uncontrolled hypertension and thus warrant further investigation.