When insufficient oxygen (O2) is supplied to the body, the resultant O2 deficit causes a deficit in energy production. This deficit may cause energy stores, such as creatine phosphate, to be used because anaerobic metabolism is too inefficient to repair the deficit. When O2 is again present in sufficient supply, excess O2 uptake is used to replenish energy stores to their original level. The long term objectives of this research are to quantify regional contributions to whole body O2 deficit/excess and to distinguish obligatory energy usage during hypoxia from facultative or temporarily dispensable activities in these regions.
Specific Aim No. 1 is to compare O2 deficit/excess in hindlimb (HL) skeletal muscle of anesthetized dogs when O2 uptake is increased by uncoupling of oxidative phosphorylation or by twitch contractions during and after hypoxia. Other experiments will measure the HL O2 deficit/excess resulting from hypoxia after the muscle O2 demand has been lowered with ouabain. These experiments will show whether excess O2 is more relatd to size of O2 deficit or to the energy imbalance.
Specific Aim No. 2 will test whether hypoxia decreases periodic isometric tension development in an in situ autoperfused muscle and whether any decrement is reflected as a greater excess O2 uptake in recovery. Sustained tetanic stimulation will deplete high-energy phosphate to near exhaustion for the same purpose in other experiments.
Specific Aim No. 3 will seek neurohumoral factors that may alter energy demand of skeletal muscle when the whole body is hypoxic by perfusing only the muscle with oxygenated blood. Discovered factors will be identified by denervation and by use of inhibitors or blockers.
Specific Aim No. 4 will utilize an in situ autoperfused gut loop in a series of experiments like dose described for muscle and will relate the results to guts's contribution to whole body O2 deficit/excess. Of special interest will be the reasons for gut's apparent non-repayment of progressively increased O2 deficit. Catecholamine calorigenesis, which is restricted to non-muscle regions, may be of particular importance in this regard. Between them, gut and muscle account for over half of the total resting O2 uptake. They are, therefore, important contributors to the body's energy economy in hypoxia. The proposed experiments will provide new insight into the nature of """"""""O2 debt"""""""" whether incurred by exercise or by hypoxia.
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