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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 306 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 15 2014 |
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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 journal › Article
}
TY - JOUR
T1 - Adaptive right ventricular performance in response to acutely increased afterload in a lamb model of congenital heart disease
T2 - Evidence for enhanced Anrep effect
AU - Johnson, Rebecca C.
AU - Datar, Sanjeev A.
AU - Oishi, Peter E.
AU - Bennett, Stephen
AU - Maki, Jun
AU - Sun, Christine
AU - Johengen, Michael
AU - He, Youping
AU - Raff, Gary W
AU - Redington, Andrew N.
AU - Fineman, Jeffrey R.
PY - 2014/4/15
Y1 - 2014/4/15
N2 - 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.
AB - 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.
KW - Cardiac performance
KW - Congenital heart disease
KW - Pressure-volume loops
KW - Pulmonary hypertension
KW - Right ventricle
UR - http://www.scopus.com/inward/record.url?scp=84900815846&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84900815846&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.01018.2013
DO - 10.1152/ajpheart.01018.2013
M3 - Article
C2 - 24561861
AN - SCOPUS:84900815846
VL - 306
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 8
ER -