Inhaled Nitric Oxide Attenuates Increased Pulmonary Artery Pressure Following Diaspirin Crosslinked Hemoglobin (Dclhb) Administration

Abstract

Intravenous administration of diaspirin crosslinked hemoglobin (DCLHb) can result in elevated pulmonary and systemic arterial pressures in some mammalian species. This study was designed to evaluate the ability of inhaled nitric oxide (INO) to attenuate elevations in pulmonary artery pressure in a closed-chested swine model. Yorkshire pigs received escalating doses of INO followed by escalating doses of DCLHb or a single dose of DCLHb followed by escalating doses of INO. Systemic and pulmonary arterial pressures were monitored continuously. Significant elevations occurred in systemic and pulmonary arterial pressure following a cumulative dose of 0.1 gm/kg DCLHb. A single dose of 0.3 gm/kg also resulted in elevations of pulmonary and systemic arterial pressure. Inhaled nitric oxide partially reversed the changes in pulmonary but not systemic pressure. These results indicate that INO might be a therapeutic option for humans who may experience increased pulmonary artery pressure following administration of DCLHb.

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

“…Scraping the endothelium also blocked the pressor effect. Nitric oxide precursors such as l -arginine and NO donors such as nitroglycerin 1128,1130,1181 or inhalation of NO attenuated the Hb-induced pressor effect. , Conversely, the potency of such agents was inhibited by Hb solutions and cGMP was reduced. ,,,,, Both free Hb and metHb were able to scavenge excess NO produced in endotoxin-treated isolated vessels in vitro . Highly purified ferrous Hbs, including oxyHb and carbonmonoxyHb (but not nitrosylated Hb), elicited dose-dependent contraction of rat aortic rings, while ferric derivatives, including metHb (whose reaction with NO is slower), did not .…”

“…Nitric oxide precursors such as L-arginine and NO donors such as nitroglycerin 1128,1130,1181 or inhalation of NO attenuated the Hb-induced pressor effect. 1182,1183 Conversely, the potency of such agents was inhibited by Hb solutions and cGMP was reduced. 305,1124,1140,1175,1180,1184 Both free Hb and metHb were able to scavenge excess NO produced in endotoxin-treated isolated vessels in vitro.…”

Effect of diaspirin cross‐linked haemoglobin (DCLHb™) on mean arterial pressure during cardiopulmonary bypass in swine

“…This hypothesis is supported by the work published by Sefton et al . who showed the antihypertensive action of inhaled NO on pulmonary pressure following DCLHb™ administration (Sefton et al ., 1999). It is important to note that, in our experiment, only Groups II and III received nicardipine infusion.…”

αα–Crosslinked Hemoglobin: Was Failure Predicted by Preclinical Testing?

“…First, hypertension could be reduced by administration of phosphoramidon, an inhibitor of the conversion of proendothelin to endothelin (a vasoactive peptide produced in endothelium) [89, 90, 91, 92]suggesting that endothelin release from endothelium plays a role. Second, administration of nitroglycerine, an NO donor [89], as well as inhaled NO [93]could mitigate the effect [94, 95]. A study with various pharmacological agents [96]showed that the hypertensive effect is not mediated by CNS mechanisms and that hemoglobin potentiates adrenergic vasoconstriction.…”