Effects of erythropoietin on advanced pulmonary vascular remodeling

¹ Depts of Pediatrics, Division of Pediatric Cardiology, Beatrix Children's Hospital
² Cardiology
³ Anesthesiology
⁴ Depts of Pediatrics, Division of Pediatric Cardiology, Beatrix Children's Hospital; and Experimental Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
⁵ Experimental Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

^* To whom correspondence should be addressed. E-mail: m.e.van.albada{at}bkk.umcg.nl.

	Abstract

Erythropoietin (EPO) mobilizes endothelial progenitor cells and promotes neovascularisation in heart failure. We studied the effects of EPO on pulmonary vascular and cardiac remodeling in a model for flow-associated pulmonary arterial hypertension (PAH).

PAH was created in adult male Wistar rats by the injection of monocrotaline combined with an abdominal aortocaval shunt one week later. Immediately afterwards, rats were randomized to treatment with EPO or control treatment. Three weeks later, pulmonary and systemic hemodynamics, and right ventricular and pulmonary vascular remodelling were evaluated.

Vascular occlusion of the intra-acinar pulmonary vessels (13.4±0.7% in PAH+EPO vs. 16.7±1.3% in PAH, p=0.038) and medial wall thickness of the pre-acinar arteries (wall to lumen ratio 0.13±0.01 in PAH+EPO vs. 0.17±0.01 in PAH, p=0.01) decreased after treatment with EPO. Moreover, right ventricular capillary density was increased by therapy (2322±61 capillaries·mm^-2 in PAH+EPO vs. 2100±63 in PAH, p=0.02). Increased mean pulmonary arterial pressure and decreased right ventricular contractility in the model were not altered by EPO treatment.

In this rat model of flow-associated PAH, EPO treatment beneficially affected pulmonary vascular and cardiac remodeling. These histopathological effects were not accompanied by significantly improved hemodynamics.