Metabolic Response of the Immature Right Ventricle to Acute Pressure Overloading [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 616.079 Immunity
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2018
• Mô tả vật lý: Size: Article No. e008570 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260220
• Chủ đề: 1. 60 applied life sciences; 2. Congenital heart disease; 3. Myocardial metabolism; 4. Right ventricle pressure loading

Tóm tắt

 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.