title: Sialyl Lewisx-containing oligosaccharide attenuates myocardial reperfusion injury in cats.
abstract: Neutrophil (PMN) adhesion to the vascular endothelium is an important mechanism of myocardial reperfusion injury. The adhesion process is initially mediated by selectins (e.g., P- and L-selectin), and monoclonal antibodies directed against these adhesion molecules exert cardioprotective activity in ischemia/reperfusion models. The counterreceptors for these selectins are thought to be carbohydrate-containing moieties. In this connection, we studied the effect of a soluble sialyl Lewisx-containing oligosaccharide (SLex-OS) on PMN-endothelial interactions in a feline model of myocardial ischemia/reperfusion (MI/R). SLex-OS (10 mg/kg), administered 10 min before R, significantly reduced myocardial necrosis compared with its vehicle 270 min after reperfusion (6 +/- 1% vs. 35 +/- 4% of area at risk, P < 0.01). The cardioprotection was confirmed by significantly lower plasma creatine kinase activities in SLex-OS vs. vehicle-treated cats (P < 0.01). Cardiac contractility (dP/dt max) of cats receiving SLex-OS was significantly preserved after 270 min of R (97 +/- 2% vs. 78 +/- 5% of initial, P < 0.01). Furthermore, endothelium-dependent relaxation to acetylcholine in coronary artery rings isolated from MI/R cats treated with SLex-OS was significantly preserved (73 +/- 7% vs. 22 +/- 6% vasorelaxation, P < 0.01). In vitro PMN adherence to coronary vascular endothelium after 270 min of R was significantly attenuated in the SLex-OS-treated group compared with the vehicle group (14 +/- 5 vs. 91 +/- 12 PMN/mm2, P < 0.01). Our results indicate that a SLex-OS is cardioprotective and preserves coronary endothelial function after MI/R, indicating an important role of sialyl Lewisx in PMN accumulation, endothelial dysfunction, and myocardial injury in myocardial ischemia/reperfusion.
authors.affiliation: Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
authors.forename: M
authors.initials: M
authors.lastname: Buerke
authors.forename: A S
authors.initials: AS
authors.lastname: Weyrich
authors.forename: Z
authors.initials: Z
authors.lastname: Zheng
authors.forename: F C
authors.initials: FC
authors.lastname: Gaeta
authors.forename: M J
authors.initials: MJ
authors.lastname: Forrest
authors.forename: A M
authors.initials: AM
authors.lastname: Lefer
mesh_terms: D000818:Animals; D002415:Cats; D002448:Cell Adhesion / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D016256:Lewis X Antigen / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009504:Neutrophils / Q000502:physiology; D009844:Oligosaccharides / Q000494:pharmacology*
chemical_list: D016256:Lewis X Antigen; D009844:Oligosaccharides