Rational treatment of respiratory disease, especially acute respiratory failure and CO2 retention in chronic diseases, is based on the understanding of CO2 control of breathing. The medullary chemoreceptors play a crucial role in regulating breathing but the mechanisms governing their activity are not established. The relation between hydrogen ion activity in medullary chemoreceptor tissue and phrenic nerve activity will be studied in anesthetized rats and cats by measuring tissue pH with a pH microelectrode during changes of arterial PCO2 and PO2. The possibility of trans-arteriolar CO2 exchange during high flow CSF perfusion will be tested by measuring tissue pH while changing arterial and CSF perfusate PCO2 in the same and in opposing directions. By measuring local tissue perfusion with a servo controlled temperature probe, with simultaneous measure of tissue pH, the response of blood flow in the chemoreceptor tissue to changes of PO2 and PCO2 and its relation to tissue hydrogen ion activity will be studied. The effect on tissue pH of the carrier mediated exchange of HCO3- across cells will be studied by measuring tissue pH response to altering arterial PCO2 before and after pharmacologic block of the HCO3 carrier. Yamamoto's hypotheses concerning the generation of CO2 by respiratory neuron activity and consequent chemoreceptor stimulation will be tested by measuring chemoreceptor pH during stimulation of the carotid sinus nerves. These studies should provide evidence to reject or accept hypotheses of chemoreceptor mechanisms which are of cardinal importance.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL029737-03
Application #
3340821
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1983-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1988-08-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Schacterle, R S; Ribando, R J; Adams, J M (1993) A model of brain arteriolar oxygen and carbon dioxide transport during anemia. J Cereb Blood Flow Metab 13:872-80
Simson, J A; Chao, J; Chao, L (1992) Localization of kallikrein gene family proteases in rat tissues. Agents Actions Suppl 38 ( Pt 1):595-602
Schacterle, R S; Adams, J M; Ribando, R J (1991) A theoretical model of gas transport between arterioles and tissue. Microvasc Res 41:210-28
Baertschi, A J; Adams, J M; Sullivan, M P (1988) Acute hypoxemia stimulates atrial natriuretic factor secretion in vivo. Am J Physiol 255:H295-300