The Influence of Anesthetics on the Functions of the Endothelium and Oxidative Stress: A Critical Review

Abstract

Endothelial dysfunction (characterized by reduced vasodilation or vasoconstriction, oxidative stress, inflammation, and pro-thrombotic condition) is a critical factor in the pathophysiology of various cardiovascular conditions, and the application of anesthetics can affect this dysfunction. Patients undergoing major surgery, especially cardiovascular surgery, are at increased risk of endothelial dysfunction. The impact of anesthetics on endothelial function can vary depending on the specific agent, dosage, duration of exposure, comorbidities, etc. Certain anesthetics, especially at higher doses, may increase the production of reactive oxygen species (ROS), leading to oxidative stress and endothelial dysfunction through reduced nitric oxid (NO) availability. Some anesthetics can modulate inflammatory responses, either by suppressing or exacerbating inflammation, or may affect the permeability of the endothelium, potentially leading to pulmonary edema and disruption of the blood-brain barrier. Anesthetics can influence endothelial glycocalyx. Understanding anesthetics effects is crucial for optimizing anesthetic management, particularly in patients with pre-existing cardiovascular issues. Therefore, the aim of this review is to critically evaluate the effects of different classes of anesthetics on endothelial function and oxidative stress. Specifically, we address how anesthetics influence NO bioavailability, endothelial glycocalyx integrity, inflammatory and oxidative pathways, and clinical outcomes in surgical patients. By summarizing current evidence, we aim to highlight mechanistic insights and identify potential perioperative strategies to minimize endothelial dysfunction.

Keywords: anesthetics; cardiovascular diseases; comorbidities; endothelium.

Figure 1

Healthy endothelium maintains a balance between opposing conditions. Endothelial cells perform paracrine-endocrine, metabolic and synthetic functions, contributing to homeostasis by maintaining balance between various processes. When damage to the endothelium occurs, the balance shifts to the predominance of the processes described on the right side of the figure.

Figure 2

Homeostatic balance between reactive oxygen species and reactive nitrogen species production in endothelium determine NO availability (above). The proposed cardioprotective effects of anesthetic propofol on decreased production of reactive oxygen species and pro-inflammatory factors, and increased production of NO and anti-inflammatory factors (below). Symbols ‘+’ and ‘-‘ indicate stimulation/increase and inhibition/decrease of the depicted effects, respectively. Abbreviations: NO—nitric oxide, O₂⁻—superoxide radical, •OH—hydroxyl radical, H₂O₂—hydrogen peroxide, ONOO⁻—peroxynitrite, eNOS—endothelial nitric oxide synthase, NADPH oxidase—nicotinamide adenine dinucleotide phosphate oxidase, SOD—superoxide dismutase, CAT—catalase.

Figure 3

The presumed effects of propofol on the synthesis of gaseous transmitters (NO, H₂S, NO), along with the depiction of key enzymes involved in the synthesis of NO (eNOS), H₂S (CSE, CBS, 3-MST) and CO (HO-1). For each listed gaseous transmitter, potential effects on the cardiovascular system are described, while on the right side of the diagram, possible pleiotropic and adverse effects of propofol are illustrated. Arrows pointing downward (↓) indicates inhibition/decrease, in the described biological processes or effects; ‘+’ indicates enhancement or promotion of the effect; ‘-’ indicates inhibition or reduction of the effect; ‘?’ indicates uncertain or unclear relationship. Abbreviations: NO-nitric oxide, CO—carbon monoxyde, H₂S—hydrogen sulfide, eNOS—endothelial nitric oxide synthase, CSE—cystathionine γ-lyase, CBS—cystathionine β-synthase, 3-MST—3-mercaptopyruvate sulfurtransferase, HO-1—heme-oxygenase 1; ROS—reactive oxygen species.