Basic fibroblast growth factor is cardioprotective in ischemia-reperfusion injury.
To examine whether basic fibroblast growth factor (bFGF) administered to the heart by perfusion can improve cardiac resistance to injury we employed an isolated rat heart model of ischemia-reperfusion injury and determined the extent of functional recovery in bFGF-treated and control hearts. Global ischemia was simulated by interruption of flow for 60 min. Recovery of developed force of contraction (DF), recorded after reestablishment of flow for 30 min, reached 63.8 +/- 1.5% and 96.5 +/- 3.5% of preischemic levels in control and bFGF-treated hearts (10 micrograms/heart), respectively, indicating that bFGF induced significantly improved recovery of mechanical function. Recoveries of the rates of contraction or relaxation were also significantly improved in bFGF-treated hearts. Extent of myocardial injury, assessed by determination of phosphocreatine kinase in the effluent, was reduced as a result of bFGF treatment. As a first step towards understanding the mechanism and direct cellular target(s) of bFGF-induced cardioprotection, we investigated its fate after perfusion. Perfusion of 10 micrograms bFGF/heart resulted in a 4-fold increase in bFGF associated with the heart compared to control levels, as estimated by biochemical fractionation and immunoblotting. Immunofluorescent staining of the bFGF-perfused hearts revealed intense anti-bFGF staining in association with blood vessels as well as the periphery of cardiomyocytes, suggesting that the latter may be a target for direct bFGF action. In conclusion, our findings of bFGF-induced increases in cardiac resistance to, and improved functional recovery from, ischemia-reperfusion injury indicate that bFGF may have clinical applications in the treatment of ischemic heart disease.
Padua
R R
RR
St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Sethi
R
R
Dhalla
N S
NS
Kardami
E
E
D000818:Animals; D003402:Creatine Kinase / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000517:prevention & control*; D015151:Immunoblotting; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D010477:Perfusion / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy
D016222:Fibroblast Growth Factor 2; D003402:Creatine Kinase