Drug Design, Development and Therapy (Feb 2020)
A Comparative Study of Inhaled Nitric Oxide and an Intravenously Administered Nitric Oxide Donor in Acute Pulmonary Hypertension
Abstract
Anna Stene Hurtsén,1,2 Ilya Zorikhin Nilsson,1 Emanuel M Dogan,1 Kristofer F Nilsson1 1Department of Cardiothoracic and Vascular Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 2Centre for Clinical Research and Education, Karlstad Central Hospital, Karlstad, SwedenCorrespondence: Kristofer F NilssonDepartment of Cardiothoracic and Vascular Surgery, Örebro University Hospital, Örebro SE-701 85, SwedenTel +46 196020352Email [email protected]: Inhaled nitric oxide (iNO) selectively vasodilates the pulmonary circulation but the effects are sometimes insufficient. Available intravenous (iv) substances are non-selective and cause systemic side effects. The pulmonary and systemic effects of iNO and an iv mono-organic nitrite (PDNO) were compared in porcine models of acute pulmonary hypertension.Methods: In anesthetized piglets, dose–response experiments of iv PDNO at normal pulmonary arterial pressure (n=10) were executed. Dose–response experiments of iv PDNO (n=6) and iNO (n=7) were performed during pharmacologically induced pulmonary hypertension (U46619 iv). The effects of iv PDNO and iNO were also explored in 5 mins of hypoxia-induced increase in pulmonary pressure (n=2-4).Results: PDNO (15, 30, 45 and 60 nmol NO kg− 1 min− 1 iv) and iNO (5, 10, 20 and 40 ppm which corresponded to 56, 112, 227, 449 nmol NO kg− 1 min− 1, respectively) significantly decreased the U46619-increased mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR) to a similar degree without significant decreases in mean arterial pressure (MAP) or systemic vascular resistance (SVR). iNO caused increased levels of methemoglobin. At an equivalent delivered NO quantity (iNO 5 ppm and PDNO 45 nmol kg− 1 min− 1 iv), PDNO decreased PVR and SVR significantly more than iNO. Both drugs counteracted hypoxia-induced pulmonary vasoconstriction and they decreased the ratio of PVR and SVR in both settings.Conclusion: Intravenous PDNO was a more potent pulmonary vasodilator than iNO in pulmonary hypertension, with no severe side effects. Hence, this study supports the potential of iv PDNO in the treatment of acute pulmonary hypertension.Keywords: PDNO, inhaled NO, acute pulmonary hypertension, hypoxia-induced vasoconstriction, U46619
