Background. Hemoglobin-based oxygen carrier (HBOC)-201 is a cell-free modified hemoglobin solution potentially facilitating oxygen uptake and delivery in cardiovascular disorders and hemorrhagic shock. Clinical use has been hampered by vasoconstriction in the systemic and pulmonary beds. Therefore we aimed to 1) determine the possibility of counteracting HBOC-201-induced pressor effects with adenosine (ADO), 2) assess the potential roles of nitric oxide (NO) scavenging, reactive oxygen species (ROS) and endothelin (ET) in mediating the observed vasoconstriction and 3) compare these effects in resting and exercising swine. Methods. Chronically instrumented swine were studied during rest and exercise after administration of HBOC-201 alone or in combination with ADO. The role of NO was assessed by supplementation with NTG or administration of the eNOS inhibitor Nω-nitro-L-arginine. Alternative vasoactive pathways were determined via iv administration of the ETA/ETB receptor blocker, tezosentan, and a mixture of ROS scavengers. Results. The systemic and to a lesser extent the pulmonary pressor effects of HBOC-201 could be counteracted by ADO; however dosage titration was very important to avoid systemic hypotensive effects. Similarly, supplementation of NO with NTG negated the pressor effects, but required titration of the dose. The pressor response to HBOC-201 was reduced after eNOS inhibition and abolished after ETA/ETB receptor blockade, while ROS scavenging did not affect it. Conclusion. The pressor response to HBOC-201 is mediated by vasoconstriction due to NO scavenging and production of ET. Further research should explore the effect of longer acting ET receptor blockers to counteract the side-effect of hemoglobin based oxygen carriers.
- Hemoglobin-based oxygen carrier
- Nitric oxide
- Copyright © 2016, Journal of Applied Physiology