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Myocardial adenine nucleotide depletion within 1 h of acute coronary artery occlusion
H Brunvand1, J Westby, J Lekven
1Department of Surgery, University of Bergen, Haukeland Hospital, Norway.
Insights
Myocardial energy stores deplete faster in the endocardium than the epicardium during acute coronary occlusion. This difference in energy breakdown during ischemia suggests metabolic heterogeneity in the heart wall.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Ischemia Research
Background:
- Acute coronary occlusion leads to myocardial ischemia and energy depletion.
- Understanding the transmural differences in energy metabolism during ischemia is crucial for therapeutic strategies.
Purpose of the Study:
- To investigate the transmural distribution of adenine nucleotides and their degradation products in ischemic myocardium.
- To determine if differences in blood flow explain the transmural variations in energy metabolism.
Main Methods:
- High-pressure liquid chromatography was used to analyze adenine nucleotides and degradation products in myocardial tissue samples.
- Radioactive microspheres were employed to measure regional myocardial blood flow.
- Experiments were conducted on anesthetized open-chest cats following left anterior descending coronary artery (LAD) occlusion.
Main Results:
- Myocardial ATP decreased rapidly, while degradation products (adenosine, inosine, hypoxanthine, xanthine) accumulated in both epicardial and endocardial layers within 20 minutes.
- After 40-60 minutes, ATP depletion and product accumulation continued in the endocardium but stabilized in the epicardium.
- Slightly higher blood flow in the epicardium did not fully account for the preserved ATP content.
- Adenosine levels significantly decreased after 40 minutes of ischemia in both layers.
Conclusions:
- Energy store breakdown is less severe in epicardial than endocardial layers during the first hour of acute coronary occlusion.
- Transmural differences in metabolic function, not solely blood flow, contribute to heterogeneous energy metabolism during severe ischemia.
Abstract:
In anaesthetized open-chest casts with occlusion of the left anterior descending coronary artery (LAD), adenine nucleotides and degradation products were studied in small myocardial tissue samples (10-20 mg) with high-pressure liquid chromatography, and tissue blood flow was measured with radioactive microspheres 5, 10, 20, 40, and 60 min after LAD occlusion. There was a rapid and parallel decrease of myocardial ATP and accumulation of adenosine, inosine, hypoxanthine, and xanthine both in epicardial and endocardial half-layers of the ischaemic myocardium within the first 20 min of coronary occlusion. After 40 and 60 min, myocardial ATP content decreased and degradation products accumulated further in the endocardium but stabilized epicardially. Analysis of covariance showed that the slightly higher blood flow in ischaemic epicardial layers, did not explain the transmural difference in ATP content after 40 and 60 min. Adenosine decreased after 40 min of ischaemia in both wall layers reaching negligible amounts after 60 min. It is concluded that breakdown of energy stores is less severe in epicardial than in endocardial wall layers during the first hour after acute coronary occlusion in the cat heart. This transmural difference cannot be explained entirely by less severe epicardial ischaemia. Therefore, transmural heterogeneity in metabolic function during severe ischaemia may also be important.