Age-specific Increase in vasopressin-induced Coronary Microvascular Contractile Response in Patients Undergoing Cardiac Surgery.

Abstract

Objectives: To assess changes in coronary microvascular vasomotor and myogenic function in older patients (65+ years) undergoing cardioplegic arrest and cardiopulmonary bypass (CP/CPB) that may portend worse outcomes.

Background: Elderly patients are being increasingly referred for cardiac operations requiring CP/CPB, but consistently have worse outcomes. Levels of circulating vasopressin and vasopressin receptor activity are enhanced with age. Effects of vasopressin on coronary microcirculation are controversial: animal studies showing increased microvascular vasoconstriction and decreased coronary blood flow, but vasopressin-deficiency leading to vasoplegic shock postoperatively has been widely reported. We investigated the effects of age and CP/CPB on coronary arteriolar vasomotor and myogenic reactivity.

Methods: Viable coronary microvessels (<200m) were harvested from human atrial samples collected pre- and post-CP/CPB from a subset of 101 enrolled patients. Ex vivo microvascular myogenic tone and vasomotor responses to vasopressin, adenosine diphosphate, and sodium nitroprusside were assessed using video microscopy. RNA deep-sequencing and immunoblotting were used to quantify gene and protein expression, respectively.

Results: Vasopressin-induced coronary microvascular response was increased in older patients (65+ years) at baseline. CP/CPB further enhanced contractile response to vasopressin in resistance arterioles while blunting nitric oxide-mediated vasodilatory responses. Gene and protein expression relevant to vasopressin signaling varied with age and following surgery. Age and vasopressin-induced contractile response predicted cardiac index.

Conclusions: Older patients exhibited more pronounced coronary microvascular contractile response to vasopressin. CP/CPB was associated with further increased coronary microvascular contractile response accompanied by decreased vasodilatory capacity from baseline, potentially predisposing these patients to myocardial malperfusion and worse outcomes.