The long term objective of this project is to determine the physiological factors which regulate fetal breathing movements in utero. The studies are conducted using unanesthetized fetal lamb preparations in which the fetus has been prepared for the recording of various biophysical parameters, 4-5 days earlier. In the present proposal we will examine the following hypothesis: 1) Fetal apnea during the high voltage electrocortical activity state is due to the lack of carbon dioxide (CO2) oscillations in fetal arterial blood; 2) The onset of sustained respiration at birth is related to an increase in tonic central (medullary) CO2 tension secondary to a fall in cerebral blood flow; 3) The sustained fetal apnea associated with moderate fetal hypoxemia is related to a decrease in central CO2 tension secondary to a rise in cerebral blood flow and 4) lesions in the intermediate area (area S) of the ventral surface of the medulla cause a loss of chemosensitive respiratory response in the fetus. The rationale which ties these four lines of investigation together is that fetal breathing movements are regulated by tonic and phasic stimulation of central chemoreceptors. Fetal breathing movements have been proposed as an index of fetal well-being in human pregnancy. An understanding of the basic regulation of these movements is essential to the interpretation of their clinical significance. In addition, these studies may lead to a greater understanding of the pathophysiology of such neonatal conditions as apnea of prematurity and the sudden infant death syndrome.
| Bissonnette, John M; Hohimer, A Roger; Knopp, Sharon J (2010) Effect of hypoxia on expiratory muscle activity in fetal sheep. Respir Physiol Neurobiol 171:110-4 |
| Bissonnette, J M; Hohimer, A R; Knopp, S J (1997) Non-NMDA receptors modulate respiratory drive in fetal sheep. J Physiol 501 ( Pt 2):415-23 |
| Bissonnette, J M; Hohimer, A R; Knopp, S J (1995) GABAergic and glutamatergic effects on behaviour in fetal sheep. J Physiol 487 ( Pt 3):677-84 |
| Bissonnette, J M; Hohimer, A R; Knopp, S J (1994) A cholinergic mechanism involved in fetal breathing during the high voltage ECoG state. Respir Physiol 96:151-62 |
| Egerman, R S; Bissonnette, J M; Hohimer, A R (1993) The effects of centrally administered adenosine on fetal sheep heart rate accelerations. Am J Obstet Gynecol 169:866-9 |
| Bissonnette, J M; Reddington, M (1991) Autoradiographic localization of adenosine A1 receptors in brainstem of fetal sheep. Brain Res Dev Brain Res 61:111-5 |
| Bissonnette, J M; Hohimer, A R; Knopp, S J (1991) The effect of centrally administered adenosine on fetal breathing movements. Respir Physiol 84:273-85 |
| Hohimer, A R; Bissonnette, J M (1991) Vascular lactic acid infusions do not alter the incidence of fetal breathing movements or their inhibition by acute hypoxemia. Pediatr Res 29:483-6 |
| Bissonnette, J M; Hohimer, A R; Chao, C R et al. (1990) Theophylline stimulates fetal breathing movements during hypoxia. Pediatr Res 28:83-6 |
| Bissonnette, J M; Hohimer, A R; Willeke, G B (1989) Effect of asphyxia on respiratory activity in fetal sheep. J Dev Physiol 12:157-61 |
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