Fetuses with congenital heart disease (CHD) have circulatory abnormalities that may compromise cerebral oxygen delivery. We believe that some CHD fetuses with decreased cerebral oxygen supply have autoregulation of blood flow that enhances cerebral perfusion (brain sparing). We hypothesize that cerebral autoregulation occurs in CHD fetuses, and the degree of autoregulation is dependent on the specific CHD and correlates with intrauterine head circumferences. CHD fetuses were compared to normal fetuses. Data included cardiac diagnosis, cerebral and umbilical artery Doppler, head circumference, weight, and gestational age. The cerebral-to-placental resistance ratio (CPR) was assessed as a measure of cerebral autoregulation. CPR = cerebral/umbilical resistance index (RI) and RI = systolic-diastolic/systolic velocity (normal CPR > 1). CPR > 1 was found in 95% of normal vs 44% of CHD fetuses. The incidence of CPR < 1 was greatest in hypoplastic left or right heart fetuses. Compared to normal, cerebral RI was decreased in CHD fetuses. The CPR vs gestational age relationship, and the relationship among weight, head circumference, and CPR differed across normal and CHD fetuses. Fetuses > 2 kg with CHD and a CPR < 1 had smaller head circumferences than normal. Brain sparing occurs in CHD fetuses. Fetuses with single ventricular physiology are most affected. Inadequate cerebral flow in CHD fetuses, despite autoregulation, may alter brain growth.

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Infants undergoing surgery for congenital heart disease are at risk for myocardial ischemia during cardiopulmonary bypass, circulatory arrest, or low-flow states. The purpose of this study was to demonstrate the effects of sildenafil, a selective phosphodiesterase-5 (PDE-5) inhibitor on myocardial functional improvement and infarct size reduction during ischemia/reperfusion injury in infant rabbits. Infant rabbits (aged 8 wk) were treated with sildenafil citrate (0.7 mg/kg i.v.) or normal saline 30 min before sustained ischemia for 30 min and reperfusion for 3 h. Transesophageal echocardiography (TEE) was used to assess left ventricular cardiac output (LVCO) and aortic velocity time integral (VTI). After ischemia/reperfusion, risk area was demarcated by Evan's blue dye and infarct size determined by computer morphometry of triphenyltetrazolium chloride-stained sections. The sildenafil-treated group had preservation and elevation in LVCO (143% of baseline, p Ͻ 0.05) and an elevated aortic VTI (145% of baseline, p Ͻ 0.05) after 30 min of ischemia compared with the control group LVCO (72% of baseline, p Ͻ 0.05) and aortic VTI (73% of baseline, p Ͻ 0.05). This is a statistically significant increase in LVCO and aortic VTI in the sildenafil group compared with controls (n ϭ 6/group, p Ͻ 0.05).The sildenafil-treated group had significant reduction in infarct size (15.5 Ϯ 1.2 versus 33 Ϯ 2.3 in the saline group, % risk area, mean Ϯ SEM, n ϭ 10 -15/group, p Ͻ 0.05). For the first time, we have shown that sildenafil citrate promotes myocardial protection in infant rabbits as evidenced by postischemic preservation and elevation in LVCO and aortic VTI and reduction in infarct size. Each year, more than 25,000 children undergo corrective surgery for congenital heart disease. Early surgical intervention is important to promote more normal development. Infants undergoing surgery for congenital heart disease are at risk for myocardial ischemia during cardiopulmonary bypass, circulatory arrest, or low-flow states (1). Less is known about the tolerance of the infant myocardium to ischemia compared with the adult, and cardiac reserves are more limited in the infant (2). Although there is evidence that the infant myocardium may be more resilient to metabolic or ischemic injury compared with adults, the infant heart responds quite differently to cardiovascular drugs, stress, and changes in hemodynamics (3,4). Although hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, this benefit may not extend to infants. For example, poor postischemic recovery of function and increased mortality may result when this method of myocardial protection is used in children (5). Therefore, there is a need to develop novel pharmacological approaches to protect infant hearts from ischemia/ reperfusion injury.Brief episodes of ischemia protect the myocardium from more prolonged periods of ischemia, a phenomenon called ischemic preconditioning (6). A variety of other stimuli, such

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