BLOCKADE OF SELECTIN-MEDIATED LEUKOCYTE ADHESION IMPROVES POSTISCHEMIC FUNCTION IN LAMB HEARTS

Background. Leukocyte-endothelial interactions appear to have an impor tant role in ischemia/reperfusion injury and are mediated by specific leukocyte and endothelial adhesion molecules. The selectins are adhesi on molecules found on leukocytes (L-selectin) and endothelium (P and E selectin) that bind to oligosaccharide ligands containing fucose and sialic acid to mediate leukocyte rolling on the endothelium. Fucoidin is a nontoxic sulfated fucose oligosaccharide derived from seaweed tha t blocks the selectins. Methods. We tested the effects of fucoidin in an isolated blood-perfused neonatal (age range, 3 to 7 days; mean age, 4.3 days) lamb heart model undergoing 2 hours of cold cardioplegic is chemia. In group F (n = 8) fucoidin (30 mg/L) was added at initial rep erfusion. Group C (n = 9) received only cardioplegia with no reperfusi on intervention. Isovolumic maximum developed pressure and the maximum positive and negative first derivatives of pressure were measured usi ng a catheter-tip transducer in an intraventricular balloon before isc hemia and at 30 minutes of reperfusion. Coronary blood flow, myocardia l oxygen consumption, and white blood cell counts in the circulating b lood were also measured. Results. Percent recoveries of baseline maxim um developed pressure and maximum positive and negative first derivati ves of pressure in group F (86% +/- 5%, 81% +/- 10%, and 74% +/- 8%, r espectively; mean +/- standard deviation) were higher than in group C (77% +/- 5%, 70% +/- 9%, and 65% +/- 6%; p < 0.05). Group F postischem ic coronary blood flow was greater (190% +/- 35%) than in group C (102 % +/- 10%; p < 0.05). Recovery of myocardial oxygen consumption in gro up F (86% +/- 14%) was greater than group C (72% +/- 11%; p < 0.05). P ostischemic white blood cell count in group F (88% +/- 4%) was greater than in group C (81% +/- 5%; p < 0.05). Conclusions. Selectin blockad e with fucoidin resulted in better recovery of left ventricular functi on, coronary blood now, and myocardial oxygen consumption after cold i schemia, despite a higher circulating white blood cell count. These da ta support the hypothesis that endothelial-leukocyte interactions play an important role in ischemia/reperfusion and suggest that selectin b lockade may be a useful therapeutic strategy.