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The effect of ischaemia on the activity of pyruvate dehydrogenase complex in rat heart
Insights
Ischaemia
Area of Science:
- Biochemistry
- Cardiology
- Metabolic Research
Background:
- Pyruvate dehydrogenase complex (PDC) activity is crucial for cardiac energy metabolism.
- Dietary and disease states significantly alter cardiac substrate utilization and PDC regulation.
- Understanding PDC response to ischaemia is vital for cardiac protection strategies.
Purpose of the Study:
- To investigate the impact of ischaemia on active pyruvate dehydrogenase complex (PDC) concentration in rat hearts.
- To compare the effects of different dietary conditions (normal, high-fat, starvation) and alloxan-induced diabetes on PDC activity during ischaemia.
- To elucidate the mechanisms underlying PDC regulation by ischaemia, anoxia, and acidosis.
Main Methods:
- Glucose-perfused rat hearts subjected to varying flow rates (low flow, zero flow) and coronary artery ligation.
- Experimental groups included normal rats (normal diet, high-fat diet, 48h starvation) and alloxan-diabetic rats.
- Measurements of active PDC concentration under aerobic and ischaemic conditions.
Main Results:
- Global ischaemia (low flow) generally decreased active PDC concentration, except in normal rats on a normal diet during zero flow or regional ischaemia.
- Anoxia and K+ arrest mimicked ischaemia's effects, suggesting hypoxia and reduced mechanical activity as key factors.
- Aerobic PDC activity was highest in normal diet rats, followed by high-fat diet, starved, and diabetic rats, a hierarchy maintained under ischaemia.
Conclusions:
- Cardiac ischaemia differentially affects active pyruvate dehydrogenase complex (PDC) concentration based on metabolic state and type of ischaemia.
- Hypoxia, reduced mechanical activity, and acidosis appear to mediate ischaemia's impact on PDC.
- Dietary interventions and diabetes significantly alter cardiac metabolic flexibility and response to ischaemic stress.
Abstract:
The effect of ischaemia on the concentration of active pyruvate dehydrogenase complex has been investigated in glucose perfused hearts of normal rats fed a normal diet or a high fat diet or starved for 48 h; and in hearts from alloxan-diabetic rats. Global ischaemia induced by low flow (approx. 1 ml/min) lowered the concentration of active complex under most of the experimental conditions employed. Parallel studies showed that anoxia and K+ arrest of the heart had effects similar to that of ischaemia and suggested that hypoxia and decreased mechanical activity of the heart may be responsible for effects of low flow ischaemia. Evidence is reviewed that the effects of low flow ischaemia, K+ arrest and anoxia may be mediated through activation of pyruvate dehydrogenase kinase by increased reduction of mitochondrial NAD+. In hearts of normal rats on a normal diet, global ischaemia induced by zero flow and regional ischaemia induced by coronary artery ligation increased the concentration of active complex. Evidence is given that this may result from a combination of anoxia and acidosis. In aerobic perfusions at 60 mmHg, concentrations of active complex were ranked in the order: normal diet greater than high fat diet greater than 48 h starved greater than alloxan diabetic. This order was maintained when the concentration of active complex was increased by perfusion at 120 mmHg or lowered by global ischaemia induced by zero flow.