Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 288, Issue 5, Pages R1185-R1194Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00723.2004
Keywords
brain; newborn; respiration; caffeine; thermoregulation
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Funding
- NICHD NIH HHS [HD-18478] Funding Source: Medline
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Adenosine ( ADO) receptor antagonists ( aminophylline, caffeine) blunt the respiratory roll-off response to hypoxia in the newborn. This study was designed to determine the ADO receptor subtype involved in the respiratory depression. Chronically catheterized lambs of 7-16 days of age breathed via face mask a gas mixture with a fraction of inspired O-2 of 0.21 (normoxia) or 0.07 (hypoxia), while being infused intravascularly with 9-cyclopentyl-1,3-dipropylxanthine (DPCPX; ADO A(1)-receptor antagonist, n=8), ZM-241385 (ADO A(2A)-receptor antagonist, n=7), or vehicle. Ventilation was measured at 20 degrees C by a turbine transducer flowmeter. In normoxia [arterial PO2 (PaO2) of similar to 83 Torr], infusion of vehicle did not alter cardiorespiratory measurements, whereas hypoxia (PaO2 of similar to 31 Torr, 15 min) elicited biphasic effects on mean arterial pressure (transient increase), heart rate (HR; diminishing tachycardia), and minute ventilation. In the latter, hypoxia increased ventilation to a peak value of similar to 2.5 times control within the first 3 min, which was followed by a significant (P<0.05) decline to similar to 50% of the maximum increment over the subsequent 7 min. ZM-241385 abolished the hypoxic ventilatory roll-off and blunted the rate of rise in HR without affecting mean arterial pressure or rectal temperature responses. In normoxia, DPCPX increased ventilation and mean arterial pressure but did not change HR. Compared with vehicle, DPCPX did not significantly affect cardiorespiratory responses to hypoxemia (PaO2 of similar to 31 Torr, 10 min). It is concluded that 1) ADO A(2A) receptors are critically involved in the ventilatory roll-off and HR responses to hypoxia, and 2) ADO A(1) receptors, which are tonically active in cardiorespiratory control in normoxia, appear to have little impact on hypoxic ventilatory depression.
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