Metabolic Response of the Immature Right Ventricle to Acute Pressure Overloading
- Seattle Children's Research Institute, Seattle, WA (United States). Center for Integrative Brain Research
- Seattle Children's Research Institute, Seattle, WA (United States). Center for Integrative Brain Research; Seattle Children's Hospital, Seattle, WA (United States). Division of Pediatric Cardiac Surgery
- Pacific Northwest National Laboratories (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory
- Université de Montréal and Montreal Heart Institute, Montréal, Quebec (Canada). Department of Nutrition
- Seattle Children's Research Institute, Seattle, WA (United States). Center for Integrative Brain Research; Department of Pediatrics, University of Washington, Seattle, WA (United States). Division of Cardiology
Rationale: Surgical palliation of complex congenital heart disease in early infancy often includes placement of a ulmonary artery banding (PAB) which limits intraventricular left to right shunting. However, the PAB produces acute right ventricular (RV) pressure overload leading at times to hemodynamic decompensation. The mechanisms of acute RV failure secondary to pressure overloading and increased contractile energy requirements remain unclear. Objective: We tested the hypothesis that acute RV failure has an energetic basis related to limited metabolic flexibility in juvenile pigs undergoing acute PAB. Methods and Results: Twenty-two infant male mixed breed Yorkshire piglets were randomized to undergo either a sham operation (Control) or PAB yielding, over a 2-fold elevation over baseline RV systolic pressure. Carbon 13 (13C)-labeled substrates were used for analysis of RV energy metabolism. Proton nuclear magnetic resonance (1H-NMR) showed 81% lower [Phosphocreatine (PCr)]/[ATP] in PAB group. Fractional contributions of fatty acids (FAs) to citric acid cycle were significantly lower in PAB group than those in Control group (medium-chain FA; 14.5 ± 1.6 vs. 8.2 ± 1.0%, long-chain FAs; 9.3 ± 1.5 vs. 5.1 ± 1.1%, Control vs. PAB respectively) by 13C-NMR. 13C flux analysis did not identify compensatory energy utilization from lactate and glucose to citric acid cycle under acute RV pressure overload. 13C flux through the pentose phosphate pathway from glucose was low in PAB compared to Control. Conclusions: Acute RV pressure overload yielded a decrease in [PCr]/[ATP] ratio implying that ATP production could not keep pace with the increasing ATP requirement at maximally tolerated RV pressures. Relative FA oxidation decreased without a reciprocal increase in pyruvate decarboxylation. The data imply that RV inability to adjust substrate oxidation contributes to energy imbalance and potentially to contractile failure.
- Research Organization:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)
- Grant/Contract Number:
- AC05-76RL01830; R01HL60666
- OSTI ID:
- 1626241
- Alternate ID(s):
- OSTI ID: 1777116
- Report Number(s):
- PNNL-SA-128316
- Journal Information:
- Journal of the American Heart Association, Vol. 7, Issue 11; ISSN 2047-9980
- Publisher:
- American Heart Association, Inc.Copyright Statement
- Country of Publication:
- United States
- Language:
- English
Pathophysiology, adaptation, and imaging of the right ventricle in Fontan circulation
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journal | December 2018 |
Metabolic Response to Stress by the Immature Right Ventricle Exposed to Chronic Pressure Overload
|
journal | September 2019 |
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