The primary objectives of this study is to determine if treatment with CY-1503, as opposed to placebo, will reduce the severity of reperfusion injury in neonates and infants following hypothermic cardiopulmonary bypass and cardiac surery for repair or palliation of congenital heart defects. and to assess the safety of CY-1503 in this population. Background: It can be estimated that approximately 14,000 babies born annually in the U.S. will require open heart operations to correct cardiac defects. Cardiopulmonary bypass (CPB), which produces some degree of tissue ischemia, continues to be an essential component of many cardiac operations of infants and children. CPB allows the heart to be stopped so that open cardiac reparative operations can be performed. Since the initial use of CPB, improvements in bypass materials and techniques have allowed open heart surgery to be employed with lower morbidity and mortality. However, CPB continues to be an unphysiologic state due to the massive activation of inflammatory cascades resulting from blood contact with prosthetic surfaces. In some infants and children, the circulation must be arrested completely for periods of up to 60 minutes to facilitate repair of complex cardiovascular lesions by providing an operative field that is bloodless and without cannulae. For almost all intracardia operations, independent of the use of total circulartory arrest, surgically-induced myocardial ischemia and subsequent reperfusion are necessary. Following CPB, neonates and infants generally exhibit transient impairment of pulmonary, renal, and myocardial function, increased microvascular permeability producing generalized tissue edema and in some cases, neurologic injury. The rationale for testing CY1503 in this patient population relates to the potential of this compound to reduce neutrophil-associated tissue damage at sites of reperfusion injury. This effect is mediated by the ability of CY-1503 to block selectin-dependent neutrophil migration into areas of previously ischemic, reperfused tissue. CY-1503 has been shown to reduce tisse injury in a variety of animal models of ischemia-reperfusion including myocardial infarction, trauma, transplantation, and septic shock.
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