Effect of sialyl Lewis(x) oligosaccharide on myocardial and cerebral injury in the pig

Background. Although administration of the sialyl Lewis(x) oligosaccharide may reduce myocardial injury after ischemia-reperfusion, its effect on coro nary and cerebral microvascular regulation and its clinical application dur ing cardiac operation have not been examined. Methods. Pigs were placed on normothermic cardiopulmonary bypass after 30 m inutes of left anterior descending coronary artery occlusion. The hearts we re then arrested with cold high potassium cardioplegia. After 1 hour the cr oss-clamp was removed and the pigs were weaned from cardiopulmonary bypass and perfused for an additional 1 hour. CY-1503 (a sodium salt of the sialyl Lewisx oligosaccharide, n = 6) was administered before reperfusion. Six ot her pigs received saline vehicle. Endothelium-dependent relaxation of preco ntracted coronary and brain arterioles (70 to 180 mu m) to adenosine 5'-dip hosphate and endothelium-independent relaxation to sodium nitroprusside wer e studied in vitro with videomicroscopy. Control values were obtained from uninstrumented pigs. Myeloperoxidase activity in the myocardium and brain w as measured to quantify neutrophil infiltration. Cardiac function and perfu sion were assessed by left ventricular systolic pressure, maximum rate of i ncrease of left ventricular pressure, left anterior descending coronary art ery blood now and percent segmental shortening, and cerebral vascular resis tance, internal carotid artery blood now, and the constitutively expressed and inducible isoform of nitric oxide synthase mRNA were measured. Results. The impaired myocardial contractile function after ischemia and ca rdioplegia was not improved by administration of CY-1503. The reduced endot helium-dependent relaxation responses of coronary and brain arterioles duri ng ischemia followed by cardioplegia and cardiopulmonary bypass were improv ed with CY-1503, but the altered pattern of organ perfusion was not improve d. Myeloperoxidase activity was increased in the heart after ischemia-cardi oplegia and in the brain after cardiopulmonary bypass. CY-1503 reduced myel operoxidase activity in both the myocardium and in the brain. Expressions o f myocardial inducible isoform or constitutively expressed nitric oxide syn thase were not altered in the heart. Conclusions. Although the sialyl Lewis(x) oligosaccharide does reduce neutr ophil infiltration and endothelial injury in the coronary and cerebral micr ocirculation after cardiopulmonary bypass, it does not have significant ben eficial acute effects on organ perfusion or function in the myocardium or b rain. (C) 1999 by The Society of Thoracic Surgeons.