Novel putative pharmacological therapies to protect the right ventricle in pulmonary hypertension: a review of current literature

Abstract

Pulmonary hypertension (PH) is defined by elevated mean pulmonary artery pressure following the pathological remodelling of small pulmonary arteries. An increase in right ventricular (RV) afterload results in RV hypertrophy and RV failure. The pathophysiology of PH, and RV remodelling in particular, is not well understood, thus explaining, at least in part, why current PH therapies have a limited effect. Existing therapies mostly target the pulmonary circulation. Because the remodelled RV fails to support normal cardiac function, patients eventually succumb from RV failure. Developing novel therapies that directly target the function of the RV may therefore benefit patients with PH. In the past decade, several promising studies have investigated novel cardioprotective strategies in experimental models of PH. This review aims to comprehensively discuss and highlight these novel experimental approaches to confer, in the long-term, greater health benefit in patients with PH.

Figure 1

The complex nature of PH. A graphical representation of the two major anatomical sites of pathology in PH. This figure also outlines the range of factors that accompany both pulmonary vascular remodelling and RV remodelling.

Figure 2

A simplified representation of the remodelling of the pulmonary vasculature in PH. Here, it is clear how the lumen of the vessels are constricted which ultimately results in increased pressure. Adapted from Wilkins MR. 2012 (Wilkins, 2012).

Figure 3

Collation of all the molecular and cellular mechanisms invovled in the developing of RV remodelling in PH.

Figure 4

ROS and the damage they do to cellular lipids, DNA and proteins. A reduced expression and activity of antioxidant enzymes and increased ROS production lead to increased oxidative stress. Therefore, a potential role for antioxidant therapy in PH induced oxidative stress might be predicted.