Maintenance of optimal systemic blood pressure is of major importance in the care of newborn preterm infants. Such infants frequently receive volume expanders and/or intravenous inotropic drugs (most often dopamine) after birth to increase their blood pressure. They may respond to these therapies with abrupt increases in blood pressure and they may be hypoxic, increasing their risk of brain injury. Little is known about the cerebrovascular responses of the developing brain to dopamine or to acute increases in blood pressure and/or blood volume, and no studies have evaluated the cerebral responses to these perturbations combined with hypoxemia. The primary goal of this proposal is to determine the cerebral responses of normoxic and hypoxic developing fetuses to intravenous dopamine and to rapid volume expansion in order to provide a better rationale for neonatal therapeutics directed at maintaining blood pressure and preventing brain damage. Unanesthetized, chronically- catheterized fetal sheep will be used. There are four aims in this proposal:
Aim #1. To determine the cerebral responses of developing fetuses to dopamine, with and without hypoxemia. We will test the hypothesis that dopamine causes cerebral vasoconstriction in immature fetuses and impairs oxygen delivery during hypoxemia.
Aim #2. To determine cerebral responses of developing fetuses to an acute volume load; we will test the hypothesis that an acute increase in blood volume in immature fetuses decreases cerebral perfusion pressure.
Aim #3. To assess the integrity of the blood-brain barrier and to determine changes in regional brain water content which occur during acute increases in blood pressure and blood volume.
Aim #4. Using dopaminergic and-adrenergic blockers, we will test the hypothesis that exogenous dopamine causes cerebral vasoconstriction in immature but not mature, fetuses because of incomplete dopaminergic receptor development and thus, uninhibited delta-adrenergic effects. The results of these studies will provide important new information concerning the cerebrovascular and metabolic responses of the immature brain to dopamine and volume infusions and potentially offer a better rationale for neonatal therapeutic interventions in preterm infants.
| Mayock, Dennis E; Bennett, Rachel; Robinson, Roderick D et al. (2007) Dopamine does not limit fetal cerebrovascular responses to hypoxia. J Appl Physiol 102:130-4 |
| Mayock, Dennis E; Gleason, Christine A (2004) Cerebrovascular effects of rapid volume expansion in preterm fetal sheep. Pediatr Res 55:395-9 |
| Gleason, Christine A; Robinson, Roderick; Harris, Andrew P et al. (2002) Cerebrovascular effects of intravenous dopamine infusions in fetal sheep. J Appl Physiol 92:717-24 |
| Harris, A P; Robinson, R; Koehler, R C et al. (2001) Blood-brain barrier permeability during dopamine-induced hypertension in fetal sheep. J Appl Physiol 91:123-9 |
