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

Abstract

To assess changes in coronary microvascular vasomotor and myogenic function in older patients (age ≥65) undergoing cardioplegic arrest and cardiopulmonary bypass (CP/CPB) that may portend worse outcomes. 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. Viable coronary microvessels (<200  m) 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. Vasopressin-induced coronary microvascular response was increased in older patients (age ≥65) 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. 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.