Fibroblast growth factor cardioprotection against ischemia-reperfusion injury may involve K+ ATP channels.
We investigated whether the adenosine triphosphate (ATP)-sensitive K+ (K+ATP) channel that was implicated in the ischemic preconditioning (I-PC) phenomenon, has a role in the cardioprotective effects of fibroblast growth factors (FGFs). For this purpose, we administered glibenclamide, a specific K+ATP channel blocker, before acidic fibroblast growth factor (aFGF, FGF-1) treatment, in rat heart subjected to left ventricular ischemia for 20 minutes followed by reperfusion for 24 hours. Creatine kinase (CK) activity was analyzed in myocardial tissue to assess the degree of cardiac injury. FGF-1 treatment markedly maintains CK activity. This cardioprotective effect of FGF-1 was blocked by glibenclamide. As shown by ultrastructural data, Ca2+ overload and associated cardiomyocyte alterations shown in glibenclamide-treated rats were not observed in specimens from the FGF-1 group. These findings suggest that FGF serves as an effector in I-PC and support a clinical interest of these proteins for increasing myocardial ischemic tolerance.
Cuevas
P
P
Servicio de Histología, Departamento de Investigación, Hospital Ramón y Cajal, E-28034-Madrid, Spain. pedro.cuevas@hrc.es
Carceller
F
F
Martinez-Coso
V
V
Asin-Cardiel
E
E
Giménez-Gallego
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008854:Microscopy, Electron; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D005905:Glyburide