Exploring Functional Differences between the Right and Left Ventricles to Better Understand Right Ventricular Dysfunction.

Judith Bernal-Ramirez,Zully Pedrozo,Gerardo García-Rivas,Javier A Garza-Cervantes,Matias Talamilla,Magda C Díaz-Vesga,Andrea Méndez,Anay Lázaro-Alfaro,Mauricio Henríquez,Clara Quiroga,Carlos Jerjes-Sanchez,Gaetano Santulli

doi:10.1155/2021/9993060

Abstract

The right and left ventricles have traditionally been studied as individual entities. Furthermore, modifications found in diseased left ventricles are assumed to influence on right ventricle alterations, but the connection is poorly understood. In this review, we describe the differences between ventricles under physiological and pathological conditions. Understanding the mechanisms that differentiate both ventricles would facilitate a more effective use of therapeutics and broaden our knowledge of right ventricle (RV) dysfunction. RV failure is the strongest predictor of mortality in pulmonary arterial hypertension, but at present, there are no definitive therapies directly targeting RV failure. We further explore the current state of drugs and molecules that improve RV failure in experimental therapeutics and clinical trials to treat pulmonary arterial hypertension and provide evidence of their potential benefits in heart failure.

Highlights

Pulmonary arterial hypertension (PAH) is an incurable lifelimiting disease characterized by increased pulmonary hypertension secondary to pulmonary vasculature remodeling [1]
Higher Na+/Ca2+ exchanger (NCX) protein expression has been found in right ventricle (RV) than in Left ventricular (LV) [27] (Table 1), which might explain the decreased sarcoplasmic reticulum (SR) Ca2+ availability, resulting in a decreased Ca2+ transient amplitude without changes in sarco/endoplasmic reticulum Ca2+ATPase (SERCA) activity
The role of autophagy in cardiac hypertrophy is controversial; basal autophagy would be essential for the preservation of cellular homeostasis, whereas excessive autophagy or its inhibition could aggravate hypertrophy. In different models, such as LV hypertrophy induced by pressure overload or metabolic dysfunction [84, 85] and RV hypertrophy induced by monocrotaline-induced pulmonary arterial hypertension (MCT-PAH) or hypoxia [86, 87], hypertrophy would be mediated by the induction of autophagy, while its inhibition could prevent hypertrophy [85]

Summary

Introduction

Pulmonary arterial hypertension (PAH) is an incurable lifelimiting disease characterized by increased pulmonary hypertension secondary to pulmonary vasculature remodeling [1]. The increased pressure overloads the right ventricle (RV), inducing adaptative RV remodeling. RV hypertrophy decreases wall tension, but maladaptive remodeling induces RV dysfunction and right heart failure syndrome in the end stages [2]. Specific treatment includes therapies targeting endothelin, nitric oxide, and prostacyclin pathways in pulmonary arteries to decrease pulmonary pressure and prevent RV stress [3]. RV dysfunction and the patient’s response to PAH-specific treatment determine survival [5, 6], there are no therapeutic aims to improve RV dysfunction [7]. Left ventricular (LV) dysfunction mechanisms have been widely studied, and multiple therapies to improve LV failure survival are available [8]; treatment for RV dysfunction is less robust [9]. This review focuses on the underlying mechanisms that differentiate left and right ventricles in both physiological conditions and disease development

Structural and Functional Differences between the Right and Left Ventricles

Distinctions between Right and Left Ventricle Dysfunction

A Clinical and Experimental Therapeutic Approach to RV Dysfunction

Results

Final Thoughts