Effects of chronic treprostinil treatment on experimental right heart hypertrophy and failure

Abstract

In the pulmonary trunk banding model of pressure overload-induced right ventricular hypertrophy and failure, moderate- and high-dose treatment with treprostinil did not improve right ventricular function neither in compensated nor in decompensated right heart failure.

Efficacy of treprostinil in the SU5416‐hypoxia model of severe pulmonary arterial hypertension: haemodynamic benefits are not associated with improvements in arterial remodelling

“…We tested the effects of low‐dose (100 ng·kg −1 ·min −1 ; Trep‐100) and high‐dose (810 ng·kg −1 ·min −1 ; Trep‐810) treprostinil on established PAH using the rat SUHx model of severe PAH. The low and high doses of treprostinil were selected based on the previous studies that investigated the effects of treprostinil in pulmonary artery banding model and that demonstrated reversal of established PAH in MCT model (Yang et al ., ; Zhou et al ., ; Axelgaard et al ., ). To confirm a clinically relevant plasma concentration of treprostinil was achieved in our study, we analysed the plasma levels of treprostinil in naïve, vehicle, Trep‐100 and Trep‐810‐treated rats.…”

“…Axelgaard et al . has also demonstrated that the chronic treatment with treprostinil in a moderate or high dose does not reverse or attenuate RV hypertrophy or function in pulmonary artery banding model (Axelgaard et al ., ) that is contrary to the effects of iloprost (Holmboe et al ., ). Further, the lack of direct inotropic effect of PGs on isolated atrial strips from the normal and pressure‐overloaded human right hearts has been reported (Holmboe et al ., ).…”

“…Interestingly, another study from Holmboe et al, using isolated heart perfusion system, demonstrated that iloprost, treprostinil and MRE-269 improved RV function in the healthy rat hearts; however, the positive inotropic effects of these prostacyclin analogues were abolished in hypertrophied RV (Holmboe et al, 2017b). Axelgaard et al has also demonstrated that the chronic treatment with treprostinil in a moderate or high dose does not reverse or attenuate RV hypertrophy or function in pulmonary artery banding model (Axelgaard et al, 2017) that is contrary to the effects of iloprost (Holmboe et al, 2013). Further, the lack of direct inotropic effect of PGs on isolated atrial strips from the normal and pressure-overloaded human right hearts has been reported (Holmboe et al, 2017a).…”

Levosimendan improves cardiac function and myocardial efficiency in rats with right ventricular failure

“…PT banding was performed with a clip compressed to an inner diameter of 0.6 mm as described previously. 4 , 8 Three days before PT banding surgery, the rats were randomized to treatment with levosimendan 3 mg/kg/day (Orion Pharma, Espoo, Finland) (n = 13 out of 29) or vehicle (n = 16 out of 29) added to the drinking water. Control rats without PT banding received vehicle treatment.…”

“…Echocardiography was performed before PET scanning as described elsewhere. 4 , 8 On the day of PET scanning, 20 of the 40 rats were submitted to 11 C-acetate PET to determine the effect of levosimendan on RV MEE, and 20 of the 40 rats were submitted to 18 F-FDG PET to investigate potential levosimendan-induced changes in RV metabolism ( Fig. 1b and 1c ).…”