A sialyl lewisx - containing carbohydrate reduces infarct size:
evidence for the role of selectins in myocardial ischemia with
prolonged reperfusion.
Flynn, David M., Andrew J. Buda, Paul R. Jeffords, and David J. Lefer.
Department of Medicine, Cardiology Section, Tulane University
School of Medicine, 1430 Tulane Avenue, SL48, New Orleans, Louisiana
70112, U.S.A.
APStracts 3:0170H, 1996.
Previous studies have implicated the selectins (P-, and L-selectin) in
the acute phase of myocardial reperfusion injury. However, it is
unclear whether the these adhesion molecules are involved in the
pathogenesis of mycardial reperfusion associated with longer periods
of reperfusion. Dogs (n=8/group) were subjected to 90 min of coronary
ischemia and 48 hr of reperfusion. Animals were initially treated
with a 35 mg/kg intravenous bolus of a sialyl Lewisx oligosaccharide
(SLex-OS) ten minutes prior to reperfusion followed by a 1.75
mg/kg/hr infusion for the first 24 hr of reperfusion [B+I]. A control
group of dogs received a normal saline bolus followed by saline
infusion for the first 24 hr of reperfusion. In a subsequent group of
dogs treatment consisted of only the 35 mg/kg bolus of SLex-OS to
help elucidate the time course of selectin involvement. The saline
control group exhibited marked decreases in blood flow in the
ischemic-reperfused myocardium, sustained depression of left
ventricular (LV) function, an average infarct size of 29 +/- 5% of
the myocardial area-at-risk, and excessive PMN accumulation in the
infarcted myocardium after 48 hours of reperfusion. SLex-OS [B+I]
dogs exhibited significant preservation of myocardial blood flow and
LV function at 4.5 and 48 hours of reperfusion, dramatic attenuation
(56%) of infarct size (p < 0.05), and a 55% reduction (p <
0.05) in PMN accumulation compared to the saline group.
Interestingly, SLex-OS treatment exerted early (i.e. 4.5 hr)
cardioprotective effects which waned by 48 hr of reperfusion. These
results demonstrate that the selectin family of adhesion molecules
play an extended role in myocardial reperfusion injury and are not
only involved in the acute phase of this disease process.
Received 12 October 1995; accepted in final form 9 April 1996.
APS Manuscript Number H957-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96