CYCLOCREATININE INHIBITS NEUTROPHIL ACCUMULATION IN THE MYOCARDIUM OFA CANINE MODEL OF CORONARY-ARTERY OCCLUSION AND REPERFUSION

This study tests the hypothesis that the administration of cyclocreati ne before ischemia inhibits the release of neutrophil chemotactic fact ors from myocardial tissues and subsequently reduces neutrophil accumu lation into ischemic areas. Adult mongrel dogs underwent left anterior descending coronary artery occlusion for 1 h, followed by a 2-h reper fusion. Cyclocreatine-treated dogs (n = 6) were injected intravenously with cyclocreatine solution (600 mg/kg) 1 h before the experiment and during ligation of the coronary artery. Control dogs (n = 6) were inj ected with saline. Neutrophil chemotactic activity was measured in pla sma samples using standard modified Boyden chambers. In controls dogs, significantly elevated levels of chemotactic activity were recovered in blood samples taken during reperfusion (i,e., 2.8-3.5-fold; P < .00 01) as compared to base-line activity recovered before occlusion. Prel iminary biochemical characterizations revealed that the recovered chem otactic factors (via checkerboard analysis) are proteins of high molec ular weight (greater than 1 00 kDa). Biopsy samples of control hearts showed an accumulation of a large number of neutrophils in the ischemi c portions. Cyclocreatine-treated dogs, on the contrary, showed low le vels of chemotactic activity during reperfusion, which correlated with the absence of neutrophils in ischemic areas. These results indicate the capability of cyclocreatine to inhibit the release of neutrophil c hemotactic factors from ischemic myocardium, which subsequently preven ted neutrophil accumulation.