Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 306, Issue 8, Pages H1222-H1230Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01018.2013
Keywords
right ventricle; cardiac performance; pressure-volume loops; congenital heart disease; pulmonary hypertension
Funding
- National Institutes of Health [HL-61284, 5T32-HD-049303-07]
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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 x 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.
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