Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure.

Abstract

BACKGROUND:

Prostacyclin mimetics are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostanoids on right-ventricular (RV) function are unknown. We aimed to investigate the direct effects of prostacyclin mimetics on RV function in hearts with and without RV hypertrophy and failure.

METHODS:

Wistar rats were subjected to pulmonary trunk banding to induce compensated RV hypertrophy (n = 32) or manifest RV failure (n = 32). Rats without banding served as healthy controls (n = 30). The hearts were excised and perfused in a Langendorff system and subjected to iloprost, treprostinil, epoprostenol, or MRE-269 in increasing concentrations. The effect on RV function was evaluated using a balloon-tipped catheter inserted into the right ventricle.

RESULTS:

In control hearts, iloprost, treprostinil, and MRE-269 improved RV function. The effect was, however, absent in hearts with RV hypertrophy and failure. Treprostinil and MRE-269 even impaired RV function in hearts with manifest RV failure.

CONCLUSIONS:

Iloprost, treprostinil, and MRE-269 improved RV function in the healthy rat heart. RV hypertrophy abolished the positive inotropic effect, and in the failing right ventricle, MRE-269 and treprostinil impaired RV function. This may be related to changes in prostanoid receptor expression and reduced coronary flow reserve in the hypertrophic and failing right ventricle.

• Authors: Sarah Holmboe, Asger Andersen, Jacob Johnsen, Jan Møller Nielsen, Rikke Nørregaard, Hans Erik Bøtker, Lucie H Clapp, Jens Erik Nielsen-Kudsk
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 69 Issue 1 Pg. 1-12 (Jan 2017) ISSN: 1533-4023 [Electronic] United States
• PMID: 27652910 (Publication Type: Journal Article)

Chemical References

• Cardiotonic Agents
• Prostaglandins I
• Vasodilator Agents

Topics

• Animals
• Cardiotonic Agents (pharmacology, therapeutic use)
• Heart Failure (drug therapy, physiopathology)
• Hypertrophy, Right Ventricular (drug therapy, physiopathology)
• Male
• Organ Culture Techniques
• Prostaglandins I (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Treatment Outcome
• Vasodilator Agents (pharmacology, therapeutic use)
• Ventricular Function, Right (drug effects, physiology)