Adenosine and A1 selective agonists offer minimal protection against ischaemic injury to isolated rat cardiomyocytes.
OBJECTIVE
The aim was to determine if isolated rat cardiomyocytes could be protected from ischaemic cell death by preincubation with adenosine or adenosine agonists.


METHODS
Cardiomyocytes isolated from rat hearts were preincubated in the presence of adenosine, CCPA (2-chloro-N6-cyclopentyladenosine), or carbachol prior to concentration into an ischaemic slurry. Effects of glycolysis and of isoprenaline were determined by addition of iodoacetic acid or isoprenaline to the ischaemic incubates and by exclusion of glucose from all media. Rates of ischaemic contracture were determined and survival of the myocytes versus paired control preparations was determined after various times of ischaemia, following resuspension of the cells in isotonic or hypotonic media.


RESULTS
Adenosine and CCPA produced only a small reduction of the rates of contracture and death of isolated myocytes. Carbachol gave no significant protection. Neither the degree of injury of control cells nor the amount of protection by CCPA was altered in the presence of added isoprenaline. Protection was abolished by the A1 receptor blocker sulphophenyl theophylline, iodoacetic acid, and exclusion of glucose.


CONCLUSIONS
Adenosine and adenosine agonists afford a minimal degree of protection to ischaemic isolated myocytes by a glucose dependent mechanism. This protection does not appear to account for the larger degree of protection seen in intact hearts, following similar preconditioning protocols. The failure of adenosine to protect may be related to the quiescent state of isolated cardiomyocytes, or be species specific in that adenosine may not be the trigger for preconditioning in rats.
Ganote
C E
CE
Department of Veterans Affairs Medical Center, Johnson City, TN.
Armstrong
S
S
Downey
J M
JM
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D007461:Iodoacetates; C058394:2-chloro-N(6)cyclopentyladenosine; C031433:8-(4-sulfophenyl)theophylline; D002217:Carbachol; D013806:Theophylline; D000241:Adenosine; D007545:Isoproterenol; D019807:Iodoacetic Acid