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Acute hibernation decreases myocardial pyruvate carboxylation and citrate release
A R Panchal1, B Comte, H Huang
1Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
Insights
Reduced coronary blood flow significantly decreases pyruvate carboxylation and citrate release in the heart. Cardiac citric acid cycle intermediate levels remained stable during this myocardial hibernation.
Area of Science:
- Cardiovascular Physiology
- Metabolic Biochemistry
- Cardiac Energetics
Background:
- Pyruvate carboxylation contributes minimally to cardiac citric acid cycle (CAC) flux in well-perfused hearts.
- Citrate release represents a significant loss of CAC carbon.
- The impact of reduced coronary flow on these metabolic pathways is not fully understood.
Purpose of the Study:
- To investigate the effects of acute coronary flow reduction on pyruvate carboxylation and citrate release.
- To determine the impact of reduced coronary flow on cardiac tissue content of CAC intermediates.
- To elucidate the metabolic adaptations in the heart during induced myocardial hibernation.
Main Methods:
- Utilized an open-chest anesthetized swine model with controlled coronary artery blood flow.
- Induced myocardial hibernation by decreasing blood flow by 40% for 80 minutes.
- Employed intracoronary infusion of [U-(13)C(3)]lactate and [U-(13)C(3)]pyruvate to trace CAC metabolism.
Main Results:
- Myocardial hibernation caused a 65% decrease in pyruvate carboxylation.
- Net citrate release decreased by 79% during reduced coronary flow.
- Tissue content of CAC intermediates was maintained despite reduced blood flow.
Conclusions:
- Acute reduction in coronary blood flow leads to parallel decreases in pyruvate carboxylation and citrate release.
- Cardiac CAC intermediate levels are preserved during short-term myocardial hibernation.
- These findings highlight the heart's metabolic flexibility in response to reduced oxygen supply.
Abstract:
In the well-perfused heart, pyruvate carboxylation accounts for 3-6% of the citric acid cycle (CAC) flux, and CAC carbon is lost via citrate release. We investigated the effects of an acute reduction in coronary flow on these processes and on the tissue content of CAC intermediates. Measurements were made in an open-chest anesthetized swine model. Left anterior descending coronary artery blood flow was controlled by a extracorporeal perfusion circuit, and flow was decreased by 40% for 80 min to induce myocardial hibernation (n = 8). An intracoronary infusion of [U-(13)C(3)]lactate and [U-(13)C(3)]pyruvate was given to measure the entry of pyruvate into the CAC through pyruvate carboxylation from the (13)C-labeled isotopomers of CAC intermediates. Compared with normal coronary flow, myocardial hibernation resulted in parallel decreases of 65% and 79% in pyruvate carboxylation and net citrate release by the myocardium, respectively, and maintenance of the CAC intermediate content. Elevation of the arterial pyruvate concentration by 1 mM had no effect. Thus a 40% decrease in coronary blood flow resulted in a concomitant decrease in pyruvate carboxylation and citrate release as well as maintenance of the CAC intermediates.