title: Adaptive right ventricular performance in response to acutely increased afterload in a lamb model of congenital heart disease: evidence for enhanced Anrep effect.
abstract: Patients with pulmonary hypertension associated with congenital heart disease survive longer with preserved right ventricular (RV) function compared with those with primary pulmonary hypertension. The purpose of this study was to test the hypothesis that superior RV performance can be demonstrated, at baseline and when challenged with increased RV afterload, in lambs with chronic left-to-right cardiac shunts compared with control lambs. A shunt was placed between the pulmonary artery and the aorta in fetal lambs (shunt). RV pressure-volume loops were obtained 4 wk after delivery in shunt and control lambs, before and after increased afterload was applied using pulmonary artery banding (PAB). Baseline stroke volume (8.7 ± 1.8 vs. 15.8 ± 2.7 ml, P = 0.04) and cardiac index (73.0 ± 4.0 vs. 159.2 ± 25.1 ml·min(-1)·kg(-1), P = 0.02) were greater in shunts. After PAB, there was no difference in the change in cardiac index (relative to baseline) between groups; however, heart rate (HR) was greater in controls (168 ± 7.3 vs. 138 ± 6.6 beats/min, P = 0.01), and end-systolic elastance (Ees) was greater in shunts (2.63 vs. 1.31 × baseline, P = 0.02). Control lambs showed decreased mechanical efficiency (71% baseline) compared with shunts. With acute afterload challenge, both controls and shunts maintained cardiac output; however, this was via maladaptive responses in controls, while shunts maintained mechanical efficiency and increased contractility via a proposed enhanced Anrep effect-the second, slow inotropic response in the biphasic ventricular response to increased afterload, a novel finding in the RV. The mechanisms related to these physiological differences may have important therapeutic implications.
authors.affiliation: Department of Pediatrics, University of California, San Francisco, California;
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Johnson
authors.forename: Sanjeev A
authors.initials: SA
authors.lastname: Datar
authors.forename: Peter E
authors.initials: PE
authors.lastname: Oishi
authors.forename: Stephen
authors.initials: S
authors.lastname: Bennett
authors.forename: Jun
authors.initials: J
authors.lastname: Maki
authors.forename: Christine
authors.initials: C
authors.lastname: Sun
authors.forename: Michael
authors.initials: M
authors.lastname: Johengen
authors.forename: Youping
authors.initials: Y
authors.lastname: He
authors.forename: Gary W
authors.initials: GW
authors.lastname: Raff
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Redington
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Fineman
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D001011:Aorta / Q000601:surgery; D006332:Cardiomegaly; D004195:Disease Models, Animal; D005260:Female; D006330:Heart Defects, Congenital / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D009200:Myocardial Contraction; D011247:Pregnancy; D011651:Pulmonary Artery / Q000601:surgery; D012756:Sheep; D013318:Stroke Volume; D016278:Ventricular Function, Right; D017725:Ventricular Pressure
keywords: cardiac performance; congenital heart disease; pressure-volume loops; pulmonary hypertension; right ventricle