Submitted on December 29, 2003
Accepted on July 6, 2004
Age-Dependent Cerebral Hemodynamic Effects of Indomethacin in the Newborn Piglet
Derek W Brown1, David Lee2, Vazhkudai S Kumaran2, and Ting-Yim Lee1*
1 Imaging Division, Lawson Health Research Institute, London, Ontario, Canada; Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada; Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada
2 Pediatrics Department, St Joseph's Health Care London, London, Ontario, Canada
* To whom correspondence should be addressed. E-mail: tlee{at}imaging.robarts.ca.
With recent discussions in the literature regarding prophylactic use of early (within the first 12 hours after birth), low dose indomethacin to reduce the incidence and severity of intraventricular hemorrhage, knowledge pertaining to the cerebral hemodynamic effects of indomethacin in this age group is of significant interest. The cerebral circulation is known to undergo significant changes during the first few days of postnatal life. In the present study we have investigated the hypothesis that postnatal adaptive changes influence the cerebral hemodynamic response to indomethacin in an age-dependent manner. Near infrared spectroscopy (NIRS) with indocyanine green (ICG) was used to measure cerebral hemodynamics, cerebral metabolic rate of oxygen (CMRO2), and cerebral oxygen extraction fraction (OEF) in 39 newborn piglets. Piglets were grouped by age and received either 0.2 mg/kg indomethacin (14 less than 13 hours of age, 12 greater than 13 hours of age) or saline (8 less than 13 hours of age, 5 greater than 13 hours of age) infusions. In a subgroup of indomethacin treated piglets (9 less than and 7 greater than 13 hours of age) Doppler flow ultrasound was used to diagnose and monitor the presence and persistence of patent ductus arteriosus (PDA). Age was a significant factor in the cerebral hemodynamic response to indomethacin with piglets less than 13 hours of age exhibiting delayed increases in cerebral blood flow (CBF) and cerebral blood volume (CBV) at 150 minutes post indomethacin infusion.
