Sex dependent effects of cardiovascular agents on hemoglobin oxygen affinity – An ex-vivo experiment

• Published in: Journal of critical care 2025-02, Vol.85, p.154916, Article 154916
• Main Authors: Woyke, Simon, Ronzani, Marco, Mair, Norbert, Frisch, Christoph, Marcher, Katharina, Haller, Thomas, Ströhle, Mathias, Rugg, Christopher
• Format: Article
• Language: English
• Subjects: Adrenergic receptors; Adult; Atropine - pharmacology; Cardiovascular Agents - pharmacology; Catecholamines; COVID-19; Epinephrine - pharmacology; Female; Females; Gender differences; Half saturation pressure; Hemoglobin; Hemoglobins - drug effects; Hemoglobins - metabolism; Humans; Inotropics; Investigations; Male; Males; Milrinone - pharmacology; Norepinephrine - pharmacology; Oxygen - metabolism; Oxygen dissociation curve; Plasma; Sex Factors; Sexes; Simendan - pharmacology
• ISSN: 0883-9441; 1557-8615; 1557-8615
• DOI: 10.1016/j.jcrc.2024.154916

Hemoglobin‑oxygen (Hb-O2) affinity is an important determinant for oxygen delivery and oxygen extraction. Although cardiovascular agents such as noradrenaline, adrenaline, atropine, milrinone and levosimendan are widely used in intensive care units worldwide, nothing is known about their possible effects on Hb-O2 affinity. In this experimental ex-vivo trial, venous blood samples were taken from 5 male and 6 female volunteers and incubated with the particular cardiovascular agents. Oxygen dissociation curves (ODC) were measured in-vitro with a new high-throughput method. Compared to the P50 in male and female controls, a significant right-shift of the ODC was found for noradrenaline and milrinone in all participants and for levosimendan in male samples only. Adrenaline decreased Hb-O2 affinity in male samples, atropine in female samples only. All investigated agents decreased Hb-O2 affinity, with marked differences between males and females. Although the underlying mechanisms remain unclear, the extent of these effects may increase oxygen extraction at the tissue level as long as pulmonary oxygen uptake is maintained. •Adrenaline decreases hemoglobin-oxygen affinity in males, while atropine affects only females, indipendent of the dose.•Noradrenaline causes a right shift of the hemoglobin-oxygen dissociation curve in both males and females.•Levosimendan shows a decrease in hemoglobin-oxygen affinity only in males while milrinone for both males and females.•A decrease in hemoglobin-oxygen affinity can enhance tissue oxygen extraction, but an increase is preferable in severe hypoxemia.