Mechanisms of myocardial protection by adenosine-supplemented cardioplegia: differential response of calcium-independent protein kinase C isozymes.

Background: Adenosine-supplemented cardioplegia improves myocardial function after cardioplegic arrest. However, the underlying cellular mechanism(s) responsible for adenosine's protective actions remains unclear. We tested the hypothesis that protection by adenosine-supplemented cardioplegia would be associated with selective activation of protein kinase C (PKC) isozymes delta and epsilon.

Materials And Methods: Isolated rat hearts were perfused (37 degrees C, Krebs-Ringer bicarbonate buffer) for 30 min, after which baseline functional measurements were made. This was followed by 120 min of cold cardioplegic arrest at 4 degrees C with either St. Thomas No. 2 (ST#2), ST#2 + adenosine (100 microM, ADO) or ST#2 + ADO + 8-sulfophenyltheophylline (50 microM, SPT). Hearts were reperfused for 60 min and functional measurements made. Distribution of PKC isoforms was determined (immunoblotting) after 30 min of warm perfusion (No-CDPL) or after 30 min of perfusion followed by 15 min of cardioplegic arrest.

Results: ADO prevented myocardial dysfunction after cardioplegic arrest. PKC-delta did not differ in the cytosolic fraction among groups. However, ADO prevented increases in particulate fraction PKC-delta, but elicited a significant increase in the particulate fraction PKC-epsilon, while ST#2 or SPT significantly decreased the cytosolic fraction PKC-epsilon. Both functional and cellular changes associated with ADO were receptor mediated.

Conclusion: This novel, dual action of adenosine-supplemented cardioplegia on PKC isoforms may be responsible for the associated functional improvements.