Intraventricular hemorrhage is recognized as one of the more serious neurological disorders of prematurity. Recent studies have shown that it occurs in 40 to 60% of all premature infants admitted to neonatal intensive care units and that it contributes to the death of 0.1% of all live born babies. Survivors of IVH frequently develop neurological, including intellectual, impairment as well as hydrocephalus. Numerous studies have been done in attempts to ameliorate and/or prevent this disorder, however a better understanding of the cause will be necessary before these goals can be achieved. To date various animal models, including the beagle puppy, have been used to investigate the pathogenesis of IVH. The premature rabbit delivered 5 to 3 days before term represents an alternative model which in contrast to the others is not only capable of independent, long-term survival outside the uterus but is also at risk for spontaneous germinal matrix and intraventricular hemorrhage. Lowering the intracranial pressure in these animals markedly increases the incidence of IVH, consistant with the hypothesis that IVH in the premature infant is due to the inability of the immature brain to control its volume. The hypothesis is based on the clinical observation that the premature infant loses an inordinate amount of fluid after birth and since the brain shares in the process intracranial pressure becomes subatmospheric. As a result intracranial and intravenous pressure become dissociated and the differential pressure across cerebral blood vessels increases. The increase in transmural pressure, which could be exaggerated by volume overload or increases in arterial or venous pressures, may represent the underlying force leading to hemorrhage. The object of this proposal is to use the preterm rabbit to further test the validity of this hypothesis as well as other claims concerning the pathogenesis of IVH.
