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Effect of Inhaled Nitric Oxide on Hemodynamics in Lambs with 1½ Ventricle Circulation

Kanamitsu, Hitoshi; Fujii, Yasuhiro; Centola, Luca; Kinouchi, Katsushi; Zhu, Liqun; Riemer, Robert K.; Reinhartz, Olaf

doi: 10.1097/MAT.0000000000000730
Pediatric Circulatory Support

Inhaled nitric oxide (NO) is widely used to treat postoperative pulmonary hypertension in congenital heart disease. It is believed that NO increases cardiac output (CO) by decreasing pulmonary vascular resistance (PVR), leading to increased left ventricular preload. However, the effect of NO on CO in patients with 1½ ventricle circulation remains unclear. To evaluate this, a superior cavopulmonary (SCP) shunt was constructed in 10 juvenile sheep. A PTFE graft was inserted between the superior vena cava (SVC) and the main pulmonary artery (PA). The SVC was clamped at the right atrial junction to establish a 1½ ventricle circulation. Flows, pressures, and arterial blood gases were recorded before and during inhalation of NO. Mean arterial pressure (46.6 ± 5.4 to 44.6 ± 5.9 mm Hg; p = 0.06) and left atrial pressure (4.0 ± 2.5 to 4.0 ± 2.3 mm Hg; p = 1.0) did not change. Mean PA pressure (13.6 ± 2.4 to 11.7 ± 2.9 mm Hg; p = 0.006) and PVR (5.47 ± 2.99 to 4.54 ± 2.61 Wood Units; p = 0.037) decreased significantly. SVC flow (24.8 ± 11.3 to 22.0 ± 9.7 ml/min/kg; p = 0.09) did not change, and CO decreased (140.2 ± 37.2 to 132.1 ± 39.2 ml/min/kg; p = 0.033). Arterial PO2 improved (103.72 ± 29.30 to 132.43 ± 47.02 mm Hg; p = 0.007). In this 1½ ventricle model, NO surprisingly decreased cardiac output (CO) and did not increase left ventricular preload.

From the Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California.

Submitted for consideration June 2017; accepted for publication in revised form October 2017.

Disclosures: Olaf Reinhartz had material supports from Mallinckrodt Pharmaceuticals for an INOvent drug delivery system and from W. L. Gore and Associates Inc. for ringed expanded polytetrafluoroethylene grafts. Yasuhiro Fujii was supported through a research grant from the Children’s Heart Center Research Fund, Lucile Packard Children’s Hospital, Stanford, CA.

Correspondence: Olaf Reinhartz, Department of Cardiothoracic Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305. Email:

Copyright © 2018 by the American Society for Artificial Internal Organs