The impact of nebulized epoprostenol and iloprost on hemoglobin oxygen affinity: an ex vivo experiment

Abstract

Background Inhalational prostacyclins act as strong vasodilators, potentially improving oxygenation by reducing shunt fraction and ventilation-perfusion mismatch. As prostacyclin receptors are known to be present on human erythrocytes, possible direct effects on oxygenation were further explored by examining the sole in-vitro influence of prostacyclins on hemoglobin oxygen (Hb-O2) affinity. Methods Venous blood samples from 20 healthy volunteers were exposed in-vitro to supramaximal doses of epoprostenol, iloprost, and control. By high-throughput measurements, hemoglobin oxygen dissociation curves (ODC) were derived. Hb-O2 affinity, expressed by P50 and hill coefficient, was determined, and analyzed for three subgroups: males (n= 10), females not taking (n= 4) and females taking oral contraceptives (n= 6). Results Epoprostenol significantly decreased P50 in all (27.5 (26.4 - 28.6) mmHg and 24.2 (22.7 - 25.3) mmHg; p<0.001) thereby increasing Hb-O2 affinity. Inversely, iloprost merely showed significant effects in females taking oral contraceptives where P50 was markedly increased and therefore Hb-O2 affinity decreased (28.4 (27.9 - 28.9) mmHg and 34.4 (32.2 - 36.0) mmHg; p<0.001). Conclusion Prostacyclin-receptor stimulation and subsequent cAMP mediated ATP release from erythrocytes might explain the effect of epoprostenol on Hb-O2 affinity but the reason for the sex hormone modified iloprost effect remains unclear. This finding is of great interest, as contraception is recommended for women taking iloprost. Being aware of potentially differing effects on Hb-O2 affinity might help select the right prostacyclin (epoprostenol vs. iloprost) depending on the patient and the underlying disease (e.g., acute respiratory distress syndrome vs. peripheral arterial disease).

The effect of desflurane, isoflurane and sevoflurane on the hemoglobin oxygen dissociation curve in human blood samples

“…Immediately after blood sampling, the heparinized samples were stored on ice, while blood gas analysis (ABL 800 flex, Radiometer) was performed from aliquots. Another aliquot was separated and stored at − 80 °C for the quantification of 2,3-bisphosphoglycerate (2,3-BPG) and adenosine triphosphate (ATP) concentrations with a validated liquid chromatography–tandem mass spectrometry method described before 14 .…”

The oxygen dissociation curve of blood in COVID-19–An update

“…Woyke et al exposed venous blood samples from healthy volunteers to the pulmonary vasodilators epoprostenol and iloprost (119). With epoprostenol, they detected an increased Hb-O 2 affinity in all subgroups under laboratory conditions, however, further research is required to validate this effect in vivo.…”

Comment on Ceruti et al. Temporal Changes in the Oxyhemoglobin Dissociation Curve of Critically Ill COVID-19 Patients. J. Clin. Med. 2022, 11, 788

“…Finally, drugs used for treatment might cause P 50 changes. Recently, Woyke et al [ 15 ] demonstrated in in vitro experiments that nebulized epoprostenol (a potent vasodilatory prostaglandin) significantly decreased P 50 by approximately 3 mmHg thereby increasing Hb-O 2 affinity. As inhaled epoprostenol is also used for the treatment of COVID-19 ( Identifier: NCT04452669, accessed on 8 June 2022), it would be of interest to know whether patients in the study by Ceruti and colleagues were on epoprostenol treatment.…”