Levosimendan Shows Potential to Improve Right Ventricular Function in Rat Model of PH

Levosimendan improved right ventricular function in a rat model of pulmonary hypertension, supporting its potential as an effective therapy for the disease, a study shows.

The study, “Levosimendan improves cardiac function and myocardial efficiency in rats with right ventricular failure,” was published in the journal Pulmonary Circulation.

In patients with pulmonary arterial hypertension (PAH), the heart’s right ventricular (RV) function is the most important determinant of prognosis. Essentially, in patients with pulmonary hypertension (PH), the right ventricle is subjected to a chronic pressure overload, which can lead to RV failure.

Levosimendan is currently used in the treatment of left ventricular (LV) failure. It is a calcium sensitizer known for its ability to increase heart contractibility, as well as its vasodilatory and cardioprotective effects.

In recent animal experiments, researchers showed that acute administration of levosimendan improves the function of the failing RV, and that chronic levosimendan treatment prevents the development of RV failure in a rat model of PAH.

In this study, researchers used a rat model of RV failure to assess the effects of chronic administration of levosimendan on RV function and other parameters indicative of the drug’s effectiveness.

The animals were randomized to receive seven weeks of either treatment with levosimendan or no treatment. One of the characteristics measured was myocardial external efficiency (MEE), which is the ratio between external work (conducted by the muscles of the ventricle) and oxygen consumption.

Researchers discovered that levosimendan improved RV MEE, with no change in oxygen consumption, indicating that levosimendan works by helping the ventricle work harder, improving RV failure.

“This study emphasizes the potential therapeutic value of chronic levosimendan treatment RV failure. It extends previous observations on the effect profile of levosimendan and motivates clinical testing of levosimendan in RV failure,” the researchers said.

Levosimendan is marketed as Simdax in Europe, and is approved for use in more than 60 countries but not in the U.S. Tenax Therapeutics, a specialty pharmaceutical company, acquired the North American rights to develop and market the therapy, and is investigating it as a treatment for pulmonary hypertension.

“The promising findings reported in the scientific literature provide additional support to our hypothesis that levosimendan has the potential to offer significant benefits in the treatment of pulmonary hypertension associated with heart failure and preserved ejection fraction (PH-HFpEF) patients through improvements in right heart function,” Michael Jebsen, interim CEO of Tenax Therapeutics, said in a press release.

Preserved ejection fraction refers to when the heart’s muscle contracts normally, but the ventricles do not relax as they should.

“We believe that levosimendan’s unique mechanisms of action will provide an alternative therapy for PH-HFpEF patients who currently have no effective or approved therapies to help manage their disease,” Jebsen said.

Tenax plans to advance levosimendan into a Phase 2 clinical trial to treat PH-HFpEF, which is expected to begin in the third quarter of 2018.