Biomechanics of the right ventricle in health and disease (2013 Grover Conference series)

Abstract

Right ventricular (RV) function is a major determinant of the symptomatology and outcome in pulmonary hypertension. The normal RV is a thin-walled flow generator able to accommodate large changes in venous return but unable to maintain flow output in the presence of a brisk increase in pulmonary artery pressure. The RV chronically exposed to pulmonary hypertension undergoes hypertrophic changes and an increase in contractility, allowing for preserved flow output in response to peripheral demand. Failure of systolic function adaptation (homeometric adaptation, described by Anrep's law of the heart) results in increased dimensions (heterometric adaptation; Starling's law of the heart), with a negative effect on diastolic ventricular interactions, limitation of exercise capacity, and vascular congestion. Ventricular function is described by pressure-volume relationships. The gold standard of systolic function is maximum elastance (E max), or the maximal value of the ratio of pressure to volume. This value is not immediately sensitive to changes in loading conditions. The gold standard of afterload is arterial elastance (E a), defined by the ratio of pressure at E max to stroke volume. The optimal coupling of ventricular function to the arterial circulation occurs at an E max/E a ratio between 1.5 and 2. Patients with severe pulmonary hypertension present with an increased E max, a trend toward decreased E max/E a, and increased RV dimensions, along with progression of the pulmonary vascular disease, systemic factors, and left ventricular function. The molecular mechanisms of RV systolic failure are currently being investigated. It is important to refer biological findings to sound measurements of function. Surrogates for E max and E a are being developed through bedside imaging techniques.

Keywords: afterload; arterial elastance; end-systolic elastance; maximum elastance; preload; pulmonary hypertension; right ventricle.

Figure 1

Time-course of right ventricular volume changes after a brisk increase in venous return. The initial heterometric adaptation is followed by a homeometric adaptation, allowing for a return to the initial end-diastolic volume (EDV) with decreased end-systolic volume (ESV) and increased stroke volume. Reproduced from Rosenblueth et al. with permission.

Figure 2

A, A normal right ventricular pressure-volume loop is of triangular shape, with maximum elastance (or E_es, point A) occurring before the end of systole (point B). B, A decrease in venous return allows for the recording of a family of right ventricular pressure-volume loops and the use of end-systolic pressure-volume relationship (ESPVR) and end-diastolic pressure-volume relationship (EDPVR) to define systolic and diastolic function. Reproduced from Maughan et al. with permission.

Figure 3

Single-beat method for measurement of right ventriculoarterial coupling in an anesthetized dog. A, Good agreement between directly measured maximum right ventricular (RV) pressure (P_max) when the pulmonary arterial trunk is clamped during one heart beat (black line) and extrapolated P_max (gray line). The slightly lower observed P_max is explained by the proximal pulmonary arterial compliance. B, P_max is calculated from early and late portions of the RV pressure curve, end-systolic elastance (E_es) or arterial elastance (E_a) graphically determined from P_max, and relative changes in volume and pressure during systole. Reproduced from Brimioulle et al. with permission.

Figure 4

Right ventricular (RV) pressure-volume loops with calculated maximal RV pressure (P_max), maximal elastance (E_max), and arterial elastance (E_a) in a normal subject and in a patient with pulmonary arterial hypertension (PAH). Left, source volume and pressure signals of the PAH patient (top) and a magnetic resonance image of the normal control (bottom). Right, pulmonary hypertension was associated with a marked increase in pressures and E_a, accompanied by an increase in E_max. The normal subject had an E_max/E_a ratio of 2. The E_max/E_a ratio was decreased to 1 in the PAH patient. V_es: end-systolic volume. Reproduced from Kuehne et al. with permission.

Figure 5

Decreased right ventricular (RV) maximum elastance/arterial elastance (E_max/E_a) ratio correlated with the Bax/Bcl2 ratio indicating activation of apoptosis as a universal mechanism in models of acute or chronic RV failure. Data from Rondelet et al. and Dewachter et al. PA: pulmonary artery; mRNA: messenger RNA.

Figure 6

Simplified pressure method for the determination of right ventricular (RV) maximum elastance/arterial elastance (E_es/E_a) ratio. E_max is calculated as (P_max − mPAP)/(EDV − ESV) in A and as mPAP/ESV in B. A positive V₀ is associated with a higher estimated E_max. mPAP: mean pulmonary artery pressure; P_max: maximum RV pressure; ESV: end-systolic volume; EDV: end-diastolic volume; V₀: ventricular volume at zero pressure. Reproduced from Trip et al. with permission.

Figure 7

Linear extrapolation from slightly curvilinear end-systolic pressure-volume relationships may lead to markedly different pressure or volume intercepts. In this series of 5 pressure-volume coordinates, omission of the highest or the lowest pressure point changes the zero-pressure volume intercept from a negative to a positive value.

Figure 8

Pump function curve defined by mean right ventricular pressure as a function of stroke volume (SV). The zero-SV point is calculated from a maximum-pressure determination (see Figure 3). The zero-pressure point results from a parabolic extrapolation from measured and zero-SV points. Increased preload shifts the curve in parallel to higher SV. Increased contractility increases pressure generated at any given value of SV, but in proportion to decreased SV. Reproduced from Elzinga and Westerhof with permission.

Figure 9

Right ventricular contractile reserve defined by exercise-induced increase in the systolic pressure. Reproduced from Grünig et al. with permission.