SIALYL LEWIS(X)-CONTAINING CARBOHYDRATE REDUCES INFARCT SIZE - ROLE OF SELECTINS IN MYOCARDIAL REPERFUSION INJURY

Previous studies have implicated the selectins (P- and L-selectin) in the acute phase of myocardial reperfusion injury. However, it is uncle ar whether these adhesion molecules are involved in the pathogenesis o f myocardial reperfusion associated with longer periods of reperfusion . Dogs (n = 8/group) were subjected to 90 min of coronary ischemia and 48 h of reperfusion. Animals were initially treated with a 35 mg/kg i ntravenous bolus of a sialyl Lewis(x) oligosaccharide (SLe(x)-OS) 10 m in before reperfusion, followed by a 1.75 mg . kg(-1). h(-1) infusion for the first 24 h of reperfusion. A control group of dogs received a normal saline bolus followed by saline infusion for the first 24 h of reperfusion. In a subsequent group of dogs treatment consisted of only the 35 mg/kg bolus of SLe(x)-OS to help elucidate the time course of selectin involvement. The saline control group exhibited marked decrea ses in blood Bow in the ischemic-reperfused myocardium, sustained depr ession of left ventricular function, an average infarct size of 29 +/- 5% of the myocardial area at risk, and excessive polymorphonuclear le ukocyte accumulation in the infarcted myocardium after 49 h of reperfu sion. Dogs that received a bolus followed by an infusion of SLe(x)-OS exhibited significant. preservation of myocardial blood flow and left ventricular function at 4.5 and 48 h of reperfusion, dramatic attenuat ion (56%) of infarct size (P < 0.05), and a 55% reduction (P < 0.05) i n polymorphonuclear leukocyte accumulation compared with the saline gr oup. Interestingly, SLe(x)-OS bolus treatment alone exerted early (i.e ., at 4.5 h) cardioprotective effects that waned by 48 h of reperfusio n. These results demonstrate that the selectin family of adhesion mole cules plays an extended role in myocardial reperfusion injury and is n ot only involved in the acute phase of this disease process.