Adenosine protects against hypoxic injury at hypothermia in guinea pig papillary muscles.
OBJECTIVE
To investigate the protective effects of adenosine against hypoxic injury at hypothermia; both magnitude and mechanisms.


METHODS
Receptor versus non-receptor dependent mechanisms in cardioprotection by adenosine were examined in guinea pig papillary muscles exposed to glucose free hypoxia at 24 degrees C. Contractile force amplitude (CFA) and action potential duration (APD) during increasing concentrations of adenosine at 37 degrees C, 30 degrees C and 24 degrees C normoxia were also examined.


RESULTS
CFA was significantly improved after adenosine treatment during hypothermic hypoxia compared to control (80.7+/-17.4% vs 40.5+/-10.7%, p<0.001). Adenosine receptor antagonist SPT did not antagonize (64.6+/-21.1%), and adenosine receptor agonists (APNEA+NECA) could not mimic the cardioprotection (53.8+/-9.3%). MitoK(Ca) blocker paxilline antagonized the cardioprotection (40.0+/-7.7%). During normoxic conditions hypothermia-induced increase in CFA was significantly decreased by adenosine (0.12-12 mM) whereas the increase in action potential duration was potentiated.


CONCLUSIONS
Adenosine (1.2 mM) had marked cardioprotective effect in hypothermic substrate free hypoxia. Possible mechanisms are non-receptor dependent and related to mitoK(Ca) channels. The cardiodepressive effect at hypothermia may contribute to cardioplegia.
Department of Cardiothoracic and Vascular Surgery, University Hospital of North Norway, Breivika, Tromsø, Norway. oyvind.jakobsen@fagmed.uit.no
Oyvind
O
Jakobsen
Tor
T
Steensrud
Kirsti
K
Ytrehus
Dag G
DG
Sørlie
D000200:Action Potentials; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D015687:Cell Hypoxia; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006324:Heart Arrest, Induced / Q000379:methods*; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism; D017680:Potassium Compounds / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D007211:Indoles; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D017680:Potassium Compounds; D018047:Receptors, Purinergic P1; C018369:potassium cardioplegic solution; C048220:paxilline; D000241:Adenosine