Metabolic Response of the Immature Right Ventricle to Acute Pressure Overloading
Abstract
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 citricmore »
- Authors:
-
- 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
- Publication Date:
- Research Org.:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)
- OSTI Identifier:
- 1626241
- Alternate Identifier(s):
- OSTI ID: 1777116
- Report Number(s):
- PNNL-SA-128316
Journal ID: ISSN 2047-9980
- Grant/Contract Number:
- AC05-76RL01830; R01HL60666
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of the American Heart Association
- Additional Journal Information:
- Journal Volume: 7; Journal Issue: 11; Journal ID: ISSN 2047-9980
- Publisher:
- American Heart Association, Inc.
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; myocardial metabolism; congenital heart disease; right ventricle pressure loading
Citation Formats
Kajimoto, Masaki, Nuri, Muhammad, Isern, Nancy G., Robillard‐Frayne, Isabelle, Des Rosiers, Christine, and Portman, Michael A. Metabolic Response of the Immature Right Ventricle to Acute Pressure Overloading. United States: N. p., 2018.
Web. doi:10.1161/jaha.118.008570.
Kajimoto, Masaki, Nuri, Muhammad, Isern, Nancy G., Robillard‐Frayne, Isabelle, Des Rosiers, Christine, & Portman, Michael A. Metabolic Response of the Immature Right Ventricle to Acute Pressure Overloading. United States. https://doi.org/10.1161/jaha.118.008570
Kajimoto, Masaki, Nuri, Muhammad, Isern, Nancy G., Robillard‐Frayne, Isabelle, Des Rosiers, Christine, and Portman, Michael A. Wed .
"Metabolic Response of the Immature Right Ventricle to Acute Pressure Overloading". United States. https://doi.org/10.1161/jaha.118.008570. https://www.osti.gov/servlets/purl/1626241.
@article{osti_1626241,
title = {Metabolic Response of the Immature Right Ventricle to Acute Pressure Overloading},
author = {Kajimoto, Masaki and Nuri, Muhammad and Isern, Nancy G. and Robillard‐Frayne, Isabelle and Des Rosiers, Christine and Portman, Michael A.},
abstractNote = {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.},
doi = {10.1161/jaha.118.008570},
journal = {Journal of the American Heart Association},
number = 11,
volume = 7,
place = {United States},
year = {Wed May 30 00:00:00 EDT 2018},
month = {Wed May 30 00:00:00 EDT 2018}
}
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