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Intensive Care Medicine

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01-01-2008 | Experimental

Epoprostenol treatment of acute pulmonary hypertension is associated with a paradoxical decrease in right ventricular contractility

Authors: Steffen Rex, Carlo Missant, Patrick Segers, Rolf Rossaint, Patrick F. Wouters

Published in: Intensive Care Medicine | Issue 1/2008

Abstract

Objective

Prostacyclins have been suggested to exert positive inotropic effects which would render them particularly suitable for the treatment of right ventricular (RV) dysfunction due to acute pulmonary hypertension (PHT). Data on this subject are controversial, however, and vary with the experimental conditions. We studied the inotropic effects of epoprostenol at clinically recommended doses in an experimental model of acute PHT.

Design and setting

Prospective laboratory investigation in a university hospital laboratory.

Subjects

Six pigs (36 ± 7 kg).

Interventions

Pigs were instrumented with biventricular conductance catheters, a pulmonary artery (PA) flow probe, and a high-fidelity pulmonary pressure catheter. Incremental doses of epoprostenol (10, 15, 20, 30, 40 ng kg^–1 min^–1) were administered in undiseased animals and after induction of acute hypoxia-induced PHT.

Measurements and results

In acute PHT epoprostenol markedly reduced RV afterload (slopes of pressure-flow relationship in the PA from 7.0 ± 0.6 to 4.2 ± 0.7 mmHg min l^–1). This was associated with a paradoxical and dose-dependent decrease in RV contractility (slope of preload-recruitable stroke-work relationship from 3.0 ± 0.4 to 1.6 ± 0.2 mW s ml^–1; slope of endsystolic pressure-volume relationship from 1.5 ± 0.3 to 0.7 ± 0.3 mmHg ml^–1). Left ventricular contractility was reduced only at the highest dose. In undiseased animals epoprostenol did not affect vascular tone and produced a mild biventricular decrease in contractility.

Conclusions

Epoprostenol has no positive inotropic effects in vivo. In contrast, epoprostenol-induced pulmonary vasodilation in animals with acute PHT was associated with a paradoxical decrease in RV contractility. This effect is probably caused indirectly by the close coupling of RV contractility to RV afterload. However, data from normal animals suggest that mechanisms unrelated to vasodilation are also involved in the observed negative inotropic response to epoprostenol.

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Title: Epoprostenol treatment of acute pulmonary hypertension is associated with a paradoxical decrease in right ventricular contractility
Authors: Steffen Rex
Carlo Missant
Patrick Segers
Rolf Rossaint
Patrick F. Wouters
Publication date: 01-01-2008
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 1/2008
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-007-0831-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Epoprostenol treatment of acute pulmonary hypertension is associated with a paradoxical decrease in right ventricular contractility

Abstract

Objective

Design and setting

Subjects

Interventions

Measurements and results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Design and setting

Subjects

Interventions

Measurements and results

Conclusions

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