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.


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.


CONCLUSIONS
This novel, dual action of adenosine-supplemented cardioplegia on PKC isoforms may be responsible for the associated functional improvements.
Nawas
S I
SI
Department of Surgery, University of Illinois at Chicago, 835 South Wolcott, Chicago, Illinois 60612, USA.
Schwertz
D W
DW
Beck
J M
JM
Fogelson
B G
BG
Law
W R
WR
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology*; D006324:Heart Arrest, Induced; D006439:Hemodynamics / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D011493:Protein Kinase C; D000241:Adenosine; D002118:Calcium