Hypoxia tolerance functions

Opioids depress respiration via the ji2-receptor at the level of the medulla and thereby increase PCO2. Opioids reduce respiration, an effect that is fatal in the case of overdose, by a dual action. The opioids decrease both the sensitivity of the medulla to carbon dioxide concentrations and the respiratory rate. Cardiovascular function and the response to hypoxia are not compromised. By contrast, tolerance to the respiratory depressant effects of the opioids does not appear to occur, while tolerance to the emetic effects of the opioids occurs upon repeated administration. The area postrema chemoreceptor trigger zone of the medulla mediates opioid-induced vomiting. 

In studies conducted in the 1960s in a model of complete brain ischemia in rabbits, it was shown that the duration of tolerable ischemia compatible with complete functional and histological recovery increased continuously with declining temperature, and could be extended fivefold by reducing temperature from 37°C to 25°C (18). Other workers showed that a decrease of body temperature of only 1-3°C reduced the degree of brain energy metabolite depletion and acidosis in a model of carotid ligation and hypoxia (19). 

Vanhatalo et investigated the influence of dietary nitrate supplementation on muscle metabolism and oxidative function. P MRS showed muscle PCr, P and pH changed at a faster rate in hypoxic conditions with no dietary nitrate compared to hypoxia with nitrate or normoxia conditions. The limit of tolerance to exercise was similarly affected and there was also a longer recovery of PCr under hypoxic conditions with no nitrate supplementation. Davies et assessed the impact of exercise-induced muscle damage on muscle metabolic response to dynamic exercise. Incremental knee extensor exercise was performed inside the bore of a 1.5 T magnet before, and 48 h after, executing 100 squats with a load corresponding to 70% of body mass. 

Our approach to overcoming these problems was to identify a clonal cell line that exhibited functions consistent with those observed in 02-sensing cells and to use these cells as a model system for studying the molecular basis of adaptation and tolerance to hypoxia in 02-sensing cells. We established the dopaminergic pheochromocytoma (PC 12) cell line as a reliable and valuable model for this purpose (3-7). In this chapter we shall describe and discuss outcomes from our... 

---