Adaptive right ventricular performance in response to acutely increased afterload in a lamb model of congenital heart disease: Evidence for enhanced Anrep effect

Rebecca C. Johnson, Sanjeev A. Datar, Peter E. Oishi, Stephen Bennett, Jun Maki, Christine Sun, Michael Johengen, Youping He, Gary W Raff, Andrew N. Redington, Jeffrey R. Fineman

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume306
Issue number8
DOIs
StatePublished - Apr 15 2014

Fingerprint

Pulmonary Artery
Heart Diseases
Right Ventricular Function
Ventricular Pressure
Pulmonary Hypertension
Cardiac Output
Stroke Volume
Aorta
Heart Rate
Therapeutics
Familial Primary Pulmonary Hypertension

Keywords

  • Cardiac performance
  • Congenital heart disease
  • Pressure-volume loops
  • Pulmonary hypertension
  • Right ventricle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Adaptive right ventricular performance in response to acutely increased afterload in a lamb model of congenital heart disease : Evidence for enhanced Anrep effect. / Johnson, Rebecca C.; Datar, Sanjeev A.; Oishi, Peter E.; Bennett, Stephen; Maki, Jun; Sun, Christine; Johengen, Michael; He, Youping; Raff, Gary W; Redington, Andrew N.; Fineman, Jeffrey R.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 306, No. 8, 15.04.2014.

Research output: Contribution to journalArticle

Johnson, Rebecca C. ; Datar, Sanjeev A. ; Oishi, Peter E. ; Bennett, Stephen ; Maki, Jun ; Sun, Christine ; Johengen, Michael ; He, Youping ; Raff, Gary W ; Redington, Andrew N. ; Fineman, Jeffrey R. / Adaptive right ventricular performance in response to acutely increased afterload in a lamb model of congenital heart disease : Evidence for enhanced Anrep effect. In: American Journal of Physiology - Heart and Circulatory Physiology. 2014 ; Vol. 306, No. 8.
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