Hemodynamical effects of metformin and sildenafil in the treatment of experimental pulmonary hypertension

Abstract

Metformin has been reported to have experimental effects that could be beneficial in the treatment of PH (pulmonary hypertension), though the specific mechanism of action is still under speculation. The current management of this condition is sildenafil, even in patients that requiere metformin as part of the treatment for other comorbilities. Both metformin and sildenafil effectively lower the systolic pressure in the right ventricle, however there are no reports comparing the hemodynamical effects of the two treatments. The goal of this study was to do so using a monocrotaline-induced PH rat model. The rats were divided in 5 groups, consisting of 3 treatment groups (metformin, sildenafil and combination therapy) and two control groups (positive and negative). They were followed for 60 days, at day 30 and 60 an echocardiogram was performed (ventricular ejection fraction was measured), and at day 60 cardiac catheterism was carried out, and Fulton index was estimated. No treatment scheme was effective using the right ventricle ejection fraction as a parameter. The three treatment groups had a positive response using the other outcome variables. The RVSP was improved compared to the positive (PH) controls, without reaching the negative control’s pressure regardless of the group. Fulton’s index remained pathological, but demonstrated a therapeutical effect of the pharmacological treatments. Metformin was not inferior to sildenafil in a PH rat model, interestingly combination treatment shows no hemodynamical synergy between these drugs. Safety evaluation of the kidney and liver showed no pathological or functional differences between the groups.