title: Distinct loading conditions reveal various patterns of right ventricular adaptation.
abstract: 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 + shunt). We performed pressure-volume analysis and voluntary exercise measurements at 4 wk. We compared PAB to PH (part I) and PH + 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. Frank-Starling 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 + 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.
authors.affiliation: Center for Congenital Heart Diseases, Division of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, the Netherlands. m.a.j.borgdorff@umcg.nl
authors.forename: Marinus A J
authors.initials: MA
authors.lastname: Borgdorff
authors.forename: Beatrijs
authors.initials: B
authors.lastname: Bartelds
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dickinson
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.forename: Maartje
authors.initials: M
authors.lastname: de Vroomen
authors.forename: Rolf M F
authors.initials: RM
authors.lastname: Berger
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D003250:Constriction; D004195:Disease Models, Animal; D065627:Familial Primary Pulmonary Hypertension; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008955:Models, Cardiovascular; D016686:Monocrotaline; D009200:Myocardial Contraction; D005082:Physical Exertion; D011651:Pulmonary Artery / Q000503:physiopathology / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume; D013997:Time Factors; D014463:Ultrasonography; D018497:Ventricular Dysfunction, Right / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D016278:Ventricular Function, Right; D017725:Ventricular Pressure
chemical_list: D016686:Monocrotaline
keywords: contractility; monocrotaline; pressure-volume analysis; pulmonary hypertension; right ventricular failure