In:
Journal of Cardiovascular Pharmacology, Ovid Technologies (Wolters Kluwer Health), Vol. 70, No. 4 ( 2017-10), p. 232-238
Kurzfassung:
We investigated whether chronic levosimendan treatment can prevent and revert right ventricular (RV) failure and attenuate pulmonary vascular remodeling in a rat model of pulmonary arterial hypertension (PAH). Methods and Results: PAH was induced in rats by exposure to SU5416 and hypoxia (SuHx). The rats were randomized to levosimendan (3 mg·kg −1 ·d −1 ) initiated before SuHx (n = 10, PREV), levosimendan started 6 weeks after SuHx (n = 12, REV), or vehicle treatment (n = 10, VEH). Healthy control rats received vehicle (n = 10, CONT). Ten weeks after SuHx, RV function was evaluated by echocardiography, magnetic resonance imaging, invasive pressure–volume measurements, histology, and biochemistry. Levosimendan treatment improved cardiac output (VEH vs. PREV 77 ± 7 vs. 137 ± 6 mL/min; P 〈 0.0001; VEH vs. REV 77 ± 7 vs. 117 ± 10 mL/min; P 〈 0.01) and decreased RV afterload compared with VEH (VEH vs. PREV 219 ± 33 vs. 132 ± 20 mm Hg/mL; P 〈 0.05; VEH vs. REV 219 ± 33 vs. 130 ± 11 mm Hg/mL; P 〈 0.01). In the PREV group, levosimendan restored right ventriculoarterial coupling (VEH vs. PREV 0.9 ± 0.1 vs. 1.8 ± 0.3; P 〈 0.05) and prevented the development of pulmonary arterial occlusive lesions (VEH vs. PREV 37 ± 7 vs. 15 ± 6% fully occluded lesions; P 〈 0.05). Conclusion: Chronic treatment with levosimendan prevents and reverts the development of RV failure and attenuates pulmonary vascular remodeling in a rat model of PAH.
Materialart:
Online-Ressource
ISSN:
0160-2446
DOI:
10.1097/FJC.0000000000000508
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2017
ZDB Id:
2049700-3
SSG:
15,3
Permalink