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Invited editorial on "Oxygen transport in conscious newborn dogs during hypoxic hypometabolism".
| Content Provider | Semantic Scholar |
|---|---|
| Author | Gautier, Henry |
| Copyright Year | 1998 |
| Abstract | THE OCCURRENCE OF HYPOMETABOLISM during hypoxia was initially described many years ago, and a recent renewed interest in this phenomenon probably originates from the fact that the ventilatory response to hypoxia, which is now often studied in unanesthetized animals without external temperature control, may be affected by a decrease in metabolism [oxygen uptake (V̇O2)] and consequently in body temperature (Tb) (6). Since the original study of Hill (10), it has been recognized that several factors play an important role in the development of hypoxic hypometabolism. 1) The size and age of the animal: in contrast to newborn or small adult mammals or birds with a high V̇O2 per kilogram, the hypoxic drop in metabolism is smaller in larger species, with a lower V̇O2 per kilogram (5). 2) The ambient temperature (Ta): hypoxic hypometabolism is greater at low ambient temperature, when V̇O2 is increased by thermogenesis above values observed at thermoneutrality. 3) The level of hypoxia: a drop in V̇O2 may be observed with inspired oxygen fraction (FIO2) ranging from 0.15 to 0.17 at low Ta values, whereas at normal Ta values, a decrease in V̇O2 is observed only with FIO2 at or below 0.10. It should be noted that a drop in V̇O2 may also be observed with inhalation of low concentrations of CO (7). Despite many recent studies, the mechanisms responsible for hypoxic hypometabolism remain unclear. The first possibility, proposed by Hemingway and Birzis (9), implies an effect of hypoxia on brain thermoregulatory mechanisms, resulting in a regulated decrease in Tb. As such, hypoxic hypothermia, sometimes aptly referred to as anapyrexia (2), would be the opposite of fever. In this context, it should be noted that experimentally induced fever may be reduced by hypoxia (3). A downward resetting of the thermoregulatory set point is suggested by studies showing that the Ta threshold of the thermoneutral zone, below which V̇O2 increases, is lowered in rats exposed to hypoxia (4). Similarly, it has been observed in cats exposed to heat that the Ta threshold for panting is lower in hypoxia than in normoxia (1). The hypothesis of a hypoxic lowering in Tb set point is supported by recent studies on behavioral thermoregulation, showing that many organisms, including mammals, studied in a thermocline, generally select a cooler Ta when exposed to hypoxia (8). The increase in heat losses at lower Ta in addition to the decrease in V̇O2 accentuates the hypoxic hypothermia. The way hypoxia can affect thermoregulatory centers is unknown, but several mediators (adenosine, opioids), which are released during hypoxia and which play also a role in Tb regulation, are likely to be involved in the development of hypoxic hypothermia (13). The second possibility that may account for hypoxic hypometabolism is a simple limitation in oxygen availability to the tissues. There is indirect evidence that this is unlikely because hypometabolism may occur with mild hypoxic levels, resulting in arterial PO2 (PaO2) values much higher than necessary to induce a decrease in V̇O2 of exercising muscles (see Ref. 6). In addition, even during sustained hypoxia, V̇O2 can be raised by exposure to cold or by administration of mitochondrial uncouplers (12). The above results have been obtained in adult mammals, but in the hypoxic newborn the possibility of V̇O2 being limited by the availability of oxygen has not been positively excluded. This possibility has been explored in the study of Rohlicek et al. (11) in this month’s issue of the Journal. Conscious instrumented newborn dogs aged 1–2 wk, studied at Ta values of 30 or 20°C, were exposed to sequential decreases in FIO2 from 0.21 to 0.06. V̇O2, CO2 production, and Tb were measured, and arterial and mixed venous blood samples were withdrawn through indwelling catheters, allowing determination of several indexes of oxygen transport. The results show that during normoxia V̇O2 was 70% higher at 20 than at 30°C and that during hypoxia V̇O2 started to fall significantly with a FIO2 of 0.12 at 20°C and 0.10 at 30°C. Thus, with a FIO2 of 0.10, during both warm and cold conditions, the puppies were hypometabolic, but V̇O2 was significantly higher in the cold (14.1 ml·min21 ·kg21) compared with warm conditions (11.4 ml·min21 ·kg21), despite the fact that PaO2 was slightly lower at 20°C (25 Torr) than at 30°C (30 Torr). Similarly, at the same mixed venous PO2 (Pv̄O2), which may reflect the PO2 at the tissue level, V̇O2 was higher in the cold than in warm conditions. This indicates that neither PaO2 nor Pv̄O2 was the limiting factor accounting for the hypoxic decrease in V̇O2. In addition, the linear regressions computed between V̇O2 and several indexes pertinent to blood oxygenation [e.g., PaO2, arterial oxygen content (CaO2), Pv̄O2], have greater slopes in cold compared with warm conditions, confirming that for a given level of oxygenation, even during hypoxic hypometabolism V̇O2 is higher in a cold than in a thermoneutral environment. |
| Starting Page | 314 |
| Ending Page | 316 |
| Page Count | 3 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jap.physiology.org/content/jap/84/3/761.full.pdf |
| PubMed reference number | 9480930v1 |
| Volume Number | 84 |
| Issue Number | 3 |
| Journal | Journal of applied physiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenosine Blood specimen Body Temperature Body tissue Canis familiaris Carbon Dioxide Cell Respiration Disease regression Editorial Exclusion Fever Hypothermia due to exposure Hypoxia Hypoxic-Ischemic Encephalopathy Index Indwelling Catheter Infant, Newborn Inspiration function Large Mammals Mitochondrial Diseases Muscle Opioids Oxygen measurement Oxygen measurement, partial pressure, arterial PO-2 Per Kilogram Physiologic Thermoregulation Small Thermogenesis Venous Thromboembolism oxygen transport slope torr |
| Content Type | Text |
| Resource Type | Notes |
