Right Ventricle in Pulmonary Hypertension

Abstract

During heart development chamber specification is controlled and directed by a number of genes and a fetal heart gene expression pattern is revisited during heart failure. In the setting of chronic pulmonary hypertension the right ventricle undergoes hypertrophy, which is likely initially adaptive, but often followed by decompensation, dilatation and failure. Here we discuss differences between the right ventricle and the left ventricle of the heart and begin to describe the cellular and molecular changes which characterize right heart failure. A prevention and treatment of right ventricle failure becomes a treatment goal for patients with severe pulmonary hypertension it follows that we need to understand the pathobiology of right heart hypertrophy and the transition to right heart failure.

Structural and Mechanical Adaptations of Right Ventricle Free Wall Myocardium to Pressure Overload

“…End-diastolic pressure increased significantly, as previously seen in PAB rat models (18) and as expected in the hypertensive condition. Clinically, hypertrophy has been described as the initial adaptive response to PH, in order to increase contractility (57). Here, higher dP/dt and Ees were indicative of an increase in RV contraction to maintain flow against the increased pressure afterload.…”

“…Clinically, hypertrophy is followed by progressive contractile dysfunction (57), along with chamber dilation to maintain cardiac output in spite of reduced contractility (18,57). Here, an increase in end diastolic volume was indicative of RV chamber dilation.…”

“…Moreover, sphericalization, as shown here with the change in ratio of longitudinal to circumferential length towards unity, has been associated with the onset of heart failure (see Janicki et al (36) and references therein). Eventually, RV failure occurs and is characterized by increased filling pressures, diastolic dysfunction, and decreased cardiac output (57). Tau significantly increased with PA banding from 3.8 ± 0.4 to 7.0 ± 0.3 msec, p<10 −4 , suggesting that diastolic dysfunction is occurring here in the PA banding model, and that the rats are at the onset of RV failure.…”

“…RV function is the most critical determinant of patient longevity in PH (57). Mechanistically, the RV is the end organ, in that PH leads to RV failure, which is the cause of a majority of deaths (directly or indirectly) from PH (16,25,54).…”

“…Hypertrophy of the associated myofibers occurs via an addition of sarcomeres, with evidence of fibrosis and changes to the extracellular matrix (ECM) both in humans and in rat models (4). However, the specific tissue-level compensatory adaptations of the main structural constituents of the myocardium (myofibers and collagen fibers) to pressure overload remain unknown (57). Although the effects of myocardial stress on cardiac remodeling have been studied for decades (28), the precise mechanisms by which cardiomyocytes sense the force imposed by ventricular pressure and volume overload and respond with sarcomerogenesis remains unknown (29).…”