Poorly controlled hypertension may leave the coronary microcirculation more susceptible to constriction before and after cardiac surgery. In a prospective human tissue study, Banerjee and colleagues found enhanced responses to endothelin-1 and impaired endothelium-dependent dilation in patients with uncontrolled hypertension. The findings offer a possible mechanism for myocardial vulnerability around cardioplegia and cardiopulmonary bypass, but do not establish a new drug strategy or perfusion pressure target.
Study Design and Patient Groups
The single-center study enrolled 85 patients undergoing nonemergent on-pump cardiac surgery in 2022–2023. Right atrial samples were obtained before bypass and after cross-clamp removal and separation from bypass, before protamine. Patients undergoing aortic repair or reconstruction were excluded.
The cohort included 14 patients without hypertension, 32 with well-controlled hypertension, and 39 with poorly controlled hypertension. Classification used documented history, antihypertensive prescriptions, and average clinic blood pressure during the preceding year. An average pressure below 130/80 mmHg defined the controlled groups; the uncontrolled group had average pressure at or above that threshold. These are study definitions rather than a recommendation for intraoperative management.
Investigators dissected coronary resistance arterioles from the atrial tissue and assessed their responses to endothelin-1, adenosine diphosphate, and sodium nitroprusside using video microscopy. Molecular assays, transcriptomics, and proteomics explored associated signaling pathways. Individual experiments involved subsets of the 85 patients, so the full cohort size should not be interpreted as the sample size for every laboratory result.
Poorly Controlled Hypertension and Microvascular Reactivity
Greater Endothelin-1–Induced Constriction
Before bypass, vessels from patients with uncontrolled hypertension demonstrated approximately 50% greater relative contractile response at the highest tested endothelin-1 concentration than vessels from the other two groups (P = .002). Greater responsiveness persisted after cardioplegia and bypass. Patients with controlled hypertension had responses comparable to those without hypertension.
Responses to vasopressin did not differ significantly among the hypertension groups. This distinction suggests that the observed abnormality was not simply an identical increase in responsiveness to every vasoconstrictor tested.
Impaired Endothelium-Dependent Dilation
Adenosine diphosphate–induced dilation was reduced in the uncontrolled hypertension group before and after bypass. In contrast, sodium nitroprusside, used as an endothelium-independent control, produced similar dilation across hypertension groups. The pattern is consistent with impaired endothelial regulation rather than complete loss of vascular smooth-muscle relaxation.
Bypass Blunted Responses Overall
Across the study groups, cardioplegia and bypass were associated with reduced endothelin-1–induced constriction and reduced endothelium-dependent dilation compared with pre-bypass measurements. The uncontrolled hypertension group nevertheless retained greater endothelin responsiveness relative to the comparison groups. A blunted response after bypass and a greater response between groups are different comparisons and can coexist.
Endothelin Signaling and Ventricular Function
Pretreatment with the endothelin A receptor antagonist BQ123 reduced endothelin-1–induced contraction in isolated vessels. Endothelin B receptor blockade had little effect on that contractile response. Molecular analyses also identified changes in pathways associated with vasoconstriction. These experiments support a biologically plausible mechanism, but receptor blockade in an isolated vessel does not demonstrate clinical benefit from administering an antagonist to surgical patients.
Hypertension status and echocardiographic left ventricular mass were strongly associated with endothelin-induced contraction in the study’s regression models, with reported model R² values of 0.95 before and 0.86 after cardioplegia and bypass. Associations between microvascular response and postoperative ejection-fraction change were examined in a much smaller subset of 17 patients. These exploratory models require external validation before use as bedside prediction tools.
Relevance for Perfusion Practice
The report reinforces the distinction between systemic arterial pressure and coronary microvascular behavior. A pressure measurement alone cannot describe the vessel responses assessed in this laboratory model. The study provides a physiological reason to consider chronic blood-pressure control and ventricular hypertrophy when discussing myocardial protection and recovery with the cardiac surgical team.
For perfusionists, the practical value is in understanding why patients with superficially similar systemic hemodynamics may have different myocardial responses around bypass. The study did not compare pump-flow targets, mean arterial pressure protocols, oxygen-delivery thresholds, cardioplegia formulations, or clinical vasopressor regimens. It therefore cannot identify an optimal target or show that one perfusion strategy prevents the observed dysfunction.
Although the authors propose further investigation of perioperative endothelin receptor antagonism, these data do not support routine adoption of that treatment or withholding clinically necessary hemodynamic support. Such questions require prospective clinical trials with patient-centered outcomes.
Limitations and Disclosures
This was a small observational study at one institution with laboratory experiments on surgically obtained atrial tissue. Ex vivo vessels studied under controlled, no-flow conditions cannot reproduce the complete in vivo coronary circulation, and atrial samples may not represent every ventricular microvascular bed. Small experimental subgroups, medication heterogeneity, potential confounding, and limited clinical outcome analyses constrain interpretation.
The results show associations rather than proof that hypertension caused postoperative ventricular dysfunction. They also do not prove that improving blood pressure before surgery would reverse the observed vascular changes. Findings from molecular assays and regression models should be treated as mechanistic and hypothesis-generating.
The work received National Institutes of Health support. Dr. Frank W. Sellke disclosed being a co-founder of XM-Therapeutics, with no relationship to the current study reported.
Original Article
Banerjee D, Sabe SA, Tran CT, et al. Poorly Controlled Hypertension Alters Coronary Microvascular Contractile Response to Endothelin-1 Before and After Cardiac Surgery. Journal of the American Heart Association. 2026;15:e045333. doi:10.1161/JAHA.125.045333.
This is an independently written educational synthesis. The source PDF is unchanged. The cover is an AI-generated editorial illustration, not an image of the study apparatus or a measured vessel response.
