Distinct loading conditions reveal various patterns of right ventricular adaptation

Abstract

Borgdorff MA, Bartelds B, Dickinson MG, Steendijk P, de Vroomen M, Berger RM. Distinct loading conditions reveal various patterns of right ventricular adaptation. Am J Physiol Heart Circ Physiol 305: H354 -H364, 2013. First published May 31, 2013 doi:10.1152/ajpheart.00180.2013.-Right ventricular (RV) failure due to chronically abnormal loading is a main determinant of outcome in pulmonary hypertension (PH) and congenital heart disease. However, distinct types of RV loading have been associated with different outcomes. To determine whether the adaptive RV response depends on loading type, we compared hemodynamics, exercise, and hypertrophy in models of pressure overload due to pulmonary artery banding (PAB), pressure overload due to PH, combined pressure and volume overload, and isolated volume load. Ninety-four rats were subjected to either PAB, monocrotaline-induced PH (PH), aortocaval shunt (shunt), or combined monocrotaline and aortocaval shunt (PH ϩ shunt). We performed pressure-volume analysis and voluntary exercise measurements at 4 wk. We compared PAB to PH (part I) and PH ϩ shunt to either isolated PH or shunt (part II). In part I, enhanced contractility (end-systolic elastance and preload recruitable stroke work) was present in PH and PAB, but strongest in PAB. FrankStarling mechanism was active in both PAB and PH. In PAB this was accompanied by diastolic dysfunction (increased end-diastolic elastance, relaxation constant), clinical signs of RV failure, and reduced exercise. These distinct responses were not attributable to differences in hypertrophy. In part II, in PH ϩ shunt the contractility response was blunted compared with PH, which caused pseudonormalization of parameters. Additional volume overload strongly enhanced hypertrophy in PH. We conclude that different types of loading result in distinct patterns of RV adaptation. This is of importance for the approach to patients with chronically increased RV load and for experimental studies in various types of RV failure. right ventricular failure; contractility; pressure-volume analysis; pulmonary hypertension; monocrotaline RIGHT VENTRICULAR FAILURE is a detrimental condition that is associated with significant morbidity and mortality in patients with congenital heart disease and/or pulmonary hypertension (PH) (11,19,34,38). In these conditions, persistent abnormal loading of the right ventricle (RV) leads to RV failure in the long term (17, 50). However, physiological and molecular mechanisms of RV adaptation to these abnormal loading conditions and its derailment into RV failure are largely unknown (3, 50). As a consequence, no heart failure therapy exists that specifically targets the RV. Different animal models have been used to study the abnormally loaded RV, but interpretation of data and translation to the clinical setting are hampered by conceptual concerns.First, distinct types of RV overload are used in experimental models. These include the induction of PH, where the RV interacts with an increased dynamic load due to a highresistance p...

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