Microvascular dysfunction following cardiopulmonary bypass plays a central role in postoperative organ dysfunction

Abstract

Despite significant advances in surgical technique and strategies for tissue/organ protection, cardiac surgery involving cardiopulmonary bypass is a profound stressor on the human body and is associated with numerous intraoperative and postoperative collateral effects across different tissues and organ systems. Of note, cardiopulmonary bypass has been shown to induce significant alterations in microvascular reactivity. This involves altered myogenic tone, altered microvascular responsiveness to many endogenous vasoactive agonists, and generalized endothelial dysfunction across multiple vascular beds. This review begins with a survey of in vitro studies that examine the cellular mechanisms of microvascular dysfunction following cardiac surgery involving cardiopulmonary bypass, with a focus on endothelial activation, weakened barrier integrity, altered cell surface receptor expression, and changes in the balance between vasoconstrictive and vasodilatory mediators. Microvascular dysfunction in turn influences postoperative organ dysfunction in complex, poorly understood ways. Hence the second part of this review will highlight in vivo studies examining the effects of cardiac surgery on critical organ systems, notably the heart, brain, renal system, and skin/peripheral tissue vasculature. Clinical implications and possible areas for intervention will be discussed throughout the review.

Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

“…Today, hypothermic, hyperkalemic cardioplegia under conditions of CPB is a routine, integral tool for cardiac surgeons performing a variety of cardiovascular operations. Despite its effective use in most cases, myocardial stunning [ 182 ] and injury [ 183 , 184 ] occur to some extent in most cardiovascular operations. The administration of hyperkalemic cardioplegia solution decreases myocardial oxidative stress [ 180 ].…”

“…The administration of hyperkalemic cardioplegia solution decreases myocardial oxidative stress [ 180 ]. Increased oxidative stress by myocardial ischemia, cardioplegia and CPB may affect levels of nitric oxide and other oxidative moieties and affect tissue integrity and enzyme function [ [184] , [185] , [186] ]. The restoration of blood flow to ischemic tissue after termination of cardioplegia and CPB further stimulates pathways involving oxidative processes, leading to the further generation of ROS [ [184] , [185] , [186] ].…”

“…Patients with coronary artery disease have pre-existing endothelial dysfunction which contributes to postoperative microvascular dysfunction. Microvascular changes in reactivity and permeability are well documented after cardiac surgery in the coronary circulation and in the circulation of brain, skeletal muscle and many other vascular beds [ 184 ]. In clinical studies, poorly controlled hypertension [ 176 ] or diabetes [ [207] , [208] , [209] ] are associated with a marked increase in post-operative changes in both vascular reactivity and permeability.…”

Alterations to Kidney Physiology during Cardiopulmonary Bypass—A Narrative Review of the Literature and Practical Remarks

“…These involve the use of heparin-coated CPB circuits [137], pharmacological interventions (e.g., polyethylene glycol, infliximab, sildenafil, nitro-linoleate, resveratrol, trimetazidine, and others) [135], and also aerobic exercise-induced preconditioning [138]. However, currently, there is no universal and widely accepted solution to this problem [130,139,140]. In light of this, it appears that the best strategy so far is to avoid organ ischemia during cardiac surgery to eliminate the IRI component of the generalized surgery-associated inflammatory response.…”

Myocardial tissue expression of mRNA and preoperative neutrophil-lymphocyte ratio in children undergoing congenital heart surgery

“…The inflammatory process is a physiological response to trauma and is inherent in all surgical procedures ( 1 - 5 ). However, in major surgeries, such as those involving cardiopulmonary bypass (CPB), the inflammatory response can become pathological and lead to postoperative complications due to the blood’s contact with a non-endothelial surface ( 6 - 9 ).…”