Blockade of selectin-mediated leukocyte adhesion improves postischemic function in lamb hearts.
BACKGROUND
Leukocyte-endothelial interactions appear to have a important role in ischemia/reperfusion injury and are mediated by specific leukocyte and endothelial adhesion molecules. The selectins are adhesion 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 that 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 ischemia. In group F (n = 8) fucoidin (30 mg/L) was added at initial reperfusion. Group C (n = 9) received only cardioplegia with no reperfusion intervention. Isovolumic maximum developed pressure and the maximum positive and negative first derivatives of pressure were measured using a catheter-tip transducer in an intraventricular balloon before ischemia and at 30 minutes of reperfusion. Coronary blood flow, myocardial oxygen consumption, and white blood cell counts in the circulating blood were also measured.


RESULTS
Percent recoveries of baseline maximum developed pressure and maximum positive and negative first derivatives of pressure in group F (86% +/- 5%, 81% +/- 10%, and 74% +/- 8%, respectively; mean +/- standard deviation) were higher than in group C (77% +/- 5%, 70% +/- 9%, and 65% +/- 6%; p < 0.05). Group F postischemic coronary blood flow was greater (190% +/- 35%) than in group C (102% +/- 10%; p < 0.05). Recovery of myocardial oxygen consumption in group F (86% +/- 14%) was greater than group C (72% +/- 11%; p < 0.05). Postischemic white blood cell count in group F (88% +/- 4%) was greater than in group C (81% +/- 5%; p < 0.05).


CONCLUSIONS
Selectin blockade with fucoidin resulted in better recovery of left ventricular function, coronary blood flow, and myocardial oxygen consumption after cold ischemia, despite a higher circulating white blood cell count. These data support the hypothesis that endothelial-leukocyte interactions play an important role in ischemia/reperfusion and suggest that selectin blockade may be a useful therapeutic strategy.
Department of Cardiovascular Surgery, Children's Hospital, Boston, Massachusetts 02115, USA.
T
T
Miura
D P
DP
Nelson
M L
ML
Schermerhorn
T
T
Shin'oka
G
G
Zund
P R
PR
Hickey
E J
EJ
Neufeld
J E
JE
Mayer
D000818:Animals; D000831:Animals, Newborn; D000925:Anticoagulants / Q000627:therapeutic use*; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007958:Leukocyte Count; D015425:Myocardial Reperfusion / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D010101:Oxygen Consumption; D011134:Polysaccharides / Q000627:therapeutic use*; D019087:Selectins / Q000187:drug effects*; D012756:Sheep
D000925:Anticoagulants; D011134:Polysaccharides; D019087:Selectins; C007789:fucoidan