July 5, 2001 Philadelphia, Pa. — A drug used to treat gout in adults also helps protect infants from neurological and cardiac injury after heart surgery for a high-risk birth defect, according to researchers at The Children’s Hospital of Philadelphia. The drug, allopurinol, benefited infants with hypoplastic left heart syndrome (HLHS), in which a severely underdeveloped left ventricle is unable to pump enough blood to the body.
The research team, reporting in the July 2001 issue of the journal Pediatrics, compared 131 infants with HLHS to 187 infants having lower-risk heart defects. "We found that infants with HLHS treated with allopurinol had significantly fewer seizures than those not treated, and significantly fewer cardiac events, such as acute reductions in heart and respiratory rate," said pediatric neurologist Robert R. Clancy, M.D., of Children’s Hospital, the study’s lead author. Allopurinol had no corresponding benefit for infants in the study with lower-risk heart conditions.
All 318 infants underwent heart surgery that required cardio-pulmonary bypass and deep hypothermic circulatory arrest (DHCA) – in which blood circulation is halted under low-temperature conditions. "This was the first study of neuro-cardiac protection in infants with congenital heart disease who had surgery using DHCA," added Dr. Clancy. Allopurinol caused no significant adverse effects in any of the infants studied.
Allopurinol is commonly used to treat gout in adults. Previous studies in other diseases showed allopurinol could protect the heart and nervous system. Dr. Clancy said the benefits seen in this study may result from the drug’s ability to scavenge or inhibit the production of oxygen free radicals, tissue-damaging chemicals produced during circulatory arrest.
Before reconstructive surgery was introduced in the early 1980s, HLHS was invariably fatal in early childhood. Survival rates for HLHS have been improving over the past 20 years, although children with the condition remain at a higher risk of long-term cognitive and neurological problems, compared to children with other heart defects. The complex surgery used on infants with HLHS usually requires DHCA, which raises the risk of neurological complications, in addition to any congenital brain abnormalities that may already exist.
The researchers studied 318 infants who received surgery using DHCA for congenital heart disease at The Children’s Hospital of Philadelphia between 1992 and 1997. The infants were randomized into two groups -- one group to receive allopurinol treatment, the other to receive a placebo. The study was blinded; investigators and caretakers were unaware which infants received the treatment. Of the 318 infants studied, 131 had HLHS, while 187 had other congenital heart defects, such as single-ventricle disease, transposition of the great vessels, and tetralogy of Fallot.
Researchers at Children’s Hospital have conducted numerous studies of outcomes in children receiving infant heart surgery for congenital heart defects. For instance, they recently showed that newborns with HLHS were less likely to suffer early seizures or coma when their heart defect was diagnosed before birth. Another study showed steady improvements in survival rates for children receiving surgery for HLHS, based on 15 years of experience with the surgery at Children’s Hospital.
Co-authors of the current study with Dr. Clancy included cardiac surgeons Thomas L. Spray, M.D., and J. William Gaynor, M.D.; cardiologists Gil Wernovsky, M.D., and William T. Mahle, M.D.; and cardiac anesthesiologists Susan C. Nicolson, M.D., and James M. Steven, M.D., all of the Cardiac Center at The Children’s Hospital of Philadelphia. Cardiac surgeons William I. Norwood, M.D., Ph.D., now of the A.I. duPont Hospital for Children, and Marshall L. Jacobs, M.D., of St. Christopher’s Hospital for Children, also co-authors, were at Children’s Hospital at earlier stages of the study. The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, funded the study.
Founded in 1855 as the nation's first pediatric hospital, The Children’s Hospital of Philadelphia is ranked today as the best pediatric hospital in the nation by a comprehensive Child Magazine survey. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding.
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