Effects of human relaxin-2 (serelaxin) on hypoxic pulmonary vasoconstriction during acute hypoxia in a sheep model
Received 9 February 2018
Accepted for publication 26 February 2018
Published 22 May 2018 Volume 2018:6 Pages 11—22
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Dörthe Katschinski
René Schiffner,1,2 Marius Nistor,2 Sabine Juliane Bischoff,3 Georg Matziolis,1 Martin Schmidt,4 Thomas Lehmann5
1Orthopaedic Department, 2Department of Neurology, 3Central Animal Facility, 4Institute for Biochemistry II, 5Institute of Medical Statistics, Computer Sciences and Documentation Science, Jena University Hospital, Friedrich Schiller University, Jena, Germany
Purpose: Hypoxia induces pulmonary vasoconstriction with a subsequent increase of pulmonary artery pressure (PAP), which can result in pulmonary hypertension. Serelaxin has shown an increase of pulmonary hemodynamic parameters after serelaxin injection. We therefore investigated the response of pulmonary hemodynamic parameters after serelaxin administration in a clinically relevant model.
Methods: Six controls and six sheep that received 30 μg/kg serelaxin underwent right heart catheterization during a 12-minute hypoxia period (inhalation of 5% oxygen and 95% nitrogen) and subsequent reoxygenation. Systolic, diastolic, and mean values of both PAP (respectively, PAPs, PAPd, and PAPm) and pulmonary capillary wedge pressure (respectively, PCWPs, PCWPd, and PCWPm), blood gases, heart rate (HR), and both peripheral and pulmonary arterial oxygen saturation were obtained. Cardiac output (CO), stroke volume (SV), pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAcompl), and systemic vascular resistance (SVR) were calculated.
Results: The key findings of the current study are that serelaxin prevents the rise of PAPs (p≤0.001), PAPm, PCWPm, PCWPs (p≤0.03), and PAPd (p≤0.05) during hypoxia, while it simultaneously increases CO and SV (p≤0.001). Similar courses of decreases of PAPm, PAPd, PAPs, CO, SVR (p≤0.001), and PCWPd (p≤0.03) as compared to hypoxic values were observed during reoxygenation. In direct comparison, the experimental groups differed during hypoxia in regard to HR, PAPm, PVR, and SVR (p≤0.03), and during reoxygenation in regard to HR (p≤0.001), PAPm, PAPs, PAPd, PVR, SVR (p≤0.03), and PCWPd (p≤0.05).
Conclusion: The findings of this study suggest that serelaxin treatment improves pulmonary hemodynamic parameters during acute hypoxia.
Keywords: hypoxic pulmonary vasoconstriction, pulmonary hemodynamics, relaxin-2, hypoxia, serelaxin, right heart catheterization
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