Congenital Heart Disease, Cardiac Surgery and Brain Development

Of the 30,000 infants born annually in the United States with congenital heart disease, more than one-third will require cardiac surgery in the neonatal period. Dramatic reductions in surgical mortality for such deep hypothermic cardiac surgery with cardiopulmonary bypass have been accompanied by the recognition that the survivors frequently experience adverse neurological sequelae, including cognitive deficits and other developmental disabilities. The majority of such brain injury appears to be attributable to operative events, particularly the cardiopulmonary support systems used to protect vital organs during cardiac repair. From the early 1990's a major program in this IDDRC has focused on identifying the causes of cognitive impairment during cardiac surgery. The clinical research of Newburger, du Plessis and Bellinger began to focus on the relations between deep hypothermic circulatory arrest and the subsequent functional deficits (for key initial work see Pediatrics, 1991; N. Engl. J. Med., 1993; J. Thorac. Cardiovasc. Surg., 1993; N. Engl. J. Med., 1995; Ann. Neurol., 1995). The principal findings were: 1)  the demonstration that deep hypothermic cardiac surgery using a predominantly total circulatory arrest strategy is associated with a greater risk of acute neurological complications, delayed motor development and neurological abnormalities than is surgery using a predominantly low-flow cardiopulmonary bypass strategy; and 2) the discovery, in an intraoperative study of intravascular and cellular oxygenation by near-infrared spectroscopy, of a paradoxical dissociation of changes in intravascular and mitochondrial oxygenation during hypothermic cardiopulmonary bypass, suggesting a previously unexpected impairment of mitochondrial function or of delivery of oxygen to the mitochondrion. Later work has demonstrated that the deleterious effect of circulatory arrest is nonlinear, with relatively little impact after shorter duration and steadily worsening outcomes after longer durations.  The results have led to major and beneficial changes in cardiac surgery in infants.  (Newburger and Bellinger).