Oxygen transport in conscious newborn dogs during hypoxic hypometabolism

Abstract

We questioned whether the decrease in O2 consumption (VO2) during hypoxia in newborns is a regulated response or reflects a limitation in O2 availability. Experiments were conducted on previously instrumented conscious newborn dogs. VO2 was measured at a warm ambient temperature (30 degrees C, n = 7) or in the cold (20 degrees C, n = 6), while the animals breathed air or were sequentially exposed to 15 min of fractional inspired O2 (FIO2): 21, 18, 15, 12, 10, 8, and 6%. In normoxia, VO2 averaged 15 +/- 1 (SE) and 25 +/- 1 ml . kg-1 . min-1 in warm and cold conditions, respectively. In the warm condition, hypometabolism (i.e., hypoxic VO2 < normoxic VO2) occurred at FIO2 </=10%, whereas in the cold condition, hypometabolism occurred at FIO2 </=12%. The same results were obtained in a separate group (n = 14) of noninstrumented puppies. For all levels of FIO2 with hypometabolism, the relationships between measures of O2 availability (arterial O2 saturation or content, venous PO2 or saturation, x-axis) vs. VO2 (y-axis) had lower slopes in warm than in cold conditions. Hence, VO2 during hypometabolism in the warm condition was not the maximal attainable for the level of oxygenation. The results do not support the possibility that the hypoxic drop in VO2 in the newborn reflects a limitation in O2 availability. The results are compatible with the idea that the phenomenon is one of "regulated conformism" to hypoxia.

Ventilatory and metabolic responses to hypoxia in the smallest simian primate, the pygmy marmoset

“…T b fell by ϳ2°C, which is comparable to T b changes observed in other small mammals, including primates over similar time courses (12,19). Numerous previous studies suggest a drop in the thermoregulatory set point in hypoxia (2,8,9,14,16,31,36) rather than a substrate limitation-induced hypothermia. In fact, the pygmy marmoset demonstrated an almost dose response to hypoxia, with a greater drop in T b occurring at lower O 2 levels and small drops in T b occurring at rather high levels of O 2 (Fig.…”

“…Since the 1950s, this was known to occur in a broad range of small mammals (18) and in neonates of larger mammals, including humans (10, 25). This hypoxia-induced drop in T b and metabolic depression serves a protective role by reducing O 2 demand, eliminating costly thermogenesis, improving blood O 2 affinity, and reducing the costs of ventilation (14,27,36,38,47,48). Furthermore, numerous studies support the conclusion that hypoxia resets the hypothalamic thermoregulatory set point to a lower level (9,(15)(16)(17)34), suggesting that this is a regulated process.…”

Effect of Body Warming on Regional Blood Flow Distribution in Conscious Hypoxic One-Month-Old Rabbits

“…Metabolic down-regulation is well documented during hypoxia in young or small mammals [1] including human infants [4,5] . This appears to be a regulated response [1,3,20] resulting from CNS mechanisms that lower the thermoregulatory set-point [1,21] . Metabolic down-regulation has been attributed to partial or complete suppression of thermogenesis [1,3] .…”

“…This appears to be a regulated response [1,3,20] resulting from CNS mechanisms that lower the thermoregulatory set-point [1,21] . Metabolic down-regulation has been attributed to partial or complete suppression of thermogenesis [1,3] . The further drop in V ˙ O 2 that we observed when the hypoxic infant rabbits were warmed suggests that thermogenesis had not been completely inhibited by the O 2 lack.…”

“…Animal stud-ies indicate that hypoxic hypometabolism is not due to a limitation in O 2 supply, but is a regulated decrease in O 2 demand specifi cally due to an inhibition of thermogenesis [1][2][3] . As a consequence hypoxemia in young and small mammals, including human infants, is often accompanied by a reduction in body temperature [1,[4][5][6] .…”