In this amended application, the investigators propose to study perinatal brain damage due to hypothermic cardiac arrest, as further described by their abstract: """"""""This experimental protocol, to be conducted in newborn dogs, was designed to elucidate the manner and extent to which the immature brain is protected from ischemic damage during hypothermic circulatory arrest. The rationale for this line of research relates to the well-established approach to the surgical repair of congenital cardiac defects.
Specific aims i nclude 1) measurement of regional cerebral blood flow (rCBF), regional cerebral glucose utilization (rCGU), and regional oxidative and energy metabolism during hypothermic circulatory arrest and during the recovery period; 2) determination of the safe duration of hypothermic circulatory arrest not associated with consequent ischemic brain damage; 3) investigation of the potential protection from ischemic damage of barbiturates superimposed on hypothermic circulatory arrest; and 4) therapeutic interventions prior to and during hypothermic circulatory arrest to ameliorate or reduce the extent of ischemic brain damage. Experimental procedures will involve the induction of hypothermia by surface cooling in mildly anesthetized (nitrous oxide), paralyzed and artificially ventilated newborn dogs to 20 degrees C followed by cardiac arrest for 30, 60, 90, 120 or more minutes. Thereafter, the animals will be resuscitated, following which they will undergo neuro-behavioral examination and neuropathologic analysis at 4 and 72 hours of recovery. Regional cerebral blood flow (rCBF) and glucose utilization (rCGU) will be determined during recovery from hypothermic circulatory arrest, using iodo-(14C)-anti-pyrine and 2-deoxy-(14C)-glucose as the radioisotopes. Regional oxidative and energy metabolism will be determined also during the following hypothermic circulatory arrest by the in situ analysis of concentrations of selected glycolytic and Krebs cycle intermediates and high-energy phosphate compounds, using enzymatic, fluorometric techniques. Therapeutic interventions to reduce the extent of brain damage during hypothermic cardiac arrest will include barbiturates (thiopental sodium), calcium channel blockers (flunarazne and/or nimodipin) and the xanthine oxidase inhibitor allopurinol. It is anticipated that these investigations will provide important insight into the physicochemical mechanism(s) and duration of the protective influence of hypothermic circulatory arrest on the ischemic perinatal brain.""""""""
| Yager, J Y; Christensen, M A; Vannucci, R C (1993) Regional cerebral blood flow following hypothermic circulatory arrest in newborn dogs. Brain Res 620:122-6 |
| Yager, J Y; Brucklacher, R M; Mujsce, D J et al. (1992) Cerebral oxidative metabolism during hypothermia and circulatory arrest in newborn dogs. Pediatr Res 32:547-52 |
