The purpose of this study is to investigate the efficiency of compensation and mechanisms aiming to maintain cellular oxygenation of brain, heart, and kidney of fetal and newborn lambs under abnormal conditions. Perinatal asphyxia cannot be precisely assessed. The actual """"""""state of oxygenation"""""""" of the tissues in question cannot be directly measured. Mitochondria, the sub-cellular site of oxidative phosphorylation, adapt to in vivo environmental PO2 by altering State 3, respiratory rate, and cytochrome concentration. Acutely decreased PO2 evokes a rise in State 3 activity. Chronically decreased PO2 leads to decreased cytochrome concentration. The converse is also true. The present studies will attempt to evaluate the in vivo oxygen delivery to multiple sites of fetal and neonatal lamb brain, heart, and kidney tissues and to correlate them with in vitro measurements of mitochondria respiratory activity isolated from the same segements during states of altered oxygenation. This study will also attempt to identify and compare the relative compensatory responses but the fetus and the newborn during similar hypoxic states as identified by measurements of mitochondrial respiratory activity. Using the specific response of mitochondrial respiratory activity of tissues as an indicator these studies will possibly also define critical limits endogenous to the brain, heart, and kidney at which mitochondria can no longer adapt, thereby establishing the point where ATP synthesis may be impaired and irreversible cellular damage ensues. The results of this research will add to the understanding of the final transport of oxygen to the cells and mitochondria.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD015973-03S1
Application #
3313353
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1982-01-01
Project End
1986-06-30
Budget Start
1984-01-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Goplerud, J M; Wagerle, L C; Delivoria-Papadopoulos, M (1989) Regional cerebral blood flow response during and after acute asphyxia in newborn piglets. J Appl Physiol 66:2827-32
Kurth, C D; Wagerle, L C; Delivoria-Papadopoulos, M (1988) Sympathetic regulation of cerebral blood flow during seizures in newborn lambs. Am J Physiol 255:H563-8
Wagerle, L C; Delivoria-Papadopoulos, M (1987) Alpha-adrenergic receptor subtypes in the cerebral circulation of newborn piglets. Am J Physiol 252:R1092-8
Wagerle, L C; Kumar, S P; Delivoria-Papadopoulos, M (1986) Effect of sympathetic nerve stimulation on cerebral blood flow in newborn piglets. Pediatr Res 20:131-5