The Specific Aims of the proposed research, which will be carried out in from 1-40 day old piglets, are (1) to establish for various age groups (from 1, 1-4, 10-18 and 30-40 days old) the maturation of natural breathing funcitons during quiet breathing, hypercapnia, Hering-Breuerreflex(HB) hypoxia and laryngeal stimulation. All these functions will be studied in acutely instrumented, anesthetized piglets (and in some decerebrate preparations) and part of these functions will be also studied in the chronically instrumented, unanesthetized piglet; (2) to investigate the potential role of the neuromodulator endorphin in quiet breathing, hypercapnia, hypoxia, and HB in the unanesthetized chronic piglet and to measure and correlate endorphin in brain/CSF/plasma, all in relation to maturation, and (3) to investigate the potential role of the neuromodulator adenosine on quiet breathing, hypercapnia, hypoxia and HB in the unanesthetized chronic piglet during maturation. Methodology will include radioimmunoassay for measurement of endorphin like immunoreactivity, and measurements of cardiovascular and respiratory functions, including, arterial pressure and heart rate, arterial pH and gas tensions, air flow, tidal volume, breathing frequency, airway PCO2/PO2, intratracheal and intraesophageal pressures, upper airway, inspiratory intercostal and diaphragmatic electromyogram. The long term objectives are to understand better (1) the natural maturation of respiratory control; (2) the possible role of neuromodulators such as endorphin and adenosine in this maturation; (3) whether these depressant neuromodulators are involved in postnatal abnormalities of respiratory pattern and control, and (4) the rationale for depressant neuromodulator antagonism as a therapeutic modality for treatment or prevention of such abnormalities.
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