A non-mitogenic form of acidic fibroblast growth factor reduces neutrophil infiltration in rat ischemic reperfused heart.
We studied the effects of a non-mitogenic form of acidic fibroblast growth factor (aFGF) on neutrophil infiltration in a rat model of myocardial ischemia (20 min) and reperfusion (24 hr). Neutrophil infiltration, as assessed by measurement of myeloperoxidase (MPO) activity was compared in homogenates of the infarcted left ventricle and the non-infarcted septum which was used as a reference of normal tissue. Myocardial ischemia followed by reperfusion resulted in severe myocardial injury and high cardiac MPO activity indicative of neutrophil accumulation in the ischemic myocardium. A systemic bolus (i.v.) of aFGF (2.6 microg) administered immediately after myocardial ischemia, significantly reduced (p<0.001) the MPO activity in the ischemic reperfused left ventricle compared to vehicle-treated rats. Furthermore, aFGF significantly attenuated tissue damage and neutrophil accumulation in the area at risk after myocardial ischemia and reperfusion as assessed by conventional histology. The mechanism of this protective effect appears to be related to inhibition of neutrophil extravasation, a critical step in neutrophil-induced myocardial reperfusion injury. Thus, non-mitogenic aFGF appears as an effective cardioprotective treatment for myocardial infarction.
Cuevas
P
P
Servicio de Histolog-ia, Hospital Ram-on y Cajal, Carretera de Colmenar, Km. 9,100, Madrid E-28034 Spain. pedro.cuevas@hrc.es
Carceller
F
F
Cuevas
B
B
Giménez-Gallego
G
G
Martinez-Coso
V
V
D000818:Animals; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016220:Fibroblast Growth Factor 1; D009195:Peroxidase