Changes in the PO 2 ‐dependence of oxygen consumption in the skeletal muscle of developing rats

A continuous supply of O 2 to cells in a mammalian organism is necessary to maintain normal physiological function and the microcirculation is especially important in this matter as it is the site of O 2 exchange. Under conditions of active/functional hyperemia following muscle contraction, the O 2 transport system in older subjects does not appear to respond as rapidly and to the same degree as in younger subjects. With aging, elements of the O 2 transport and regulatory system are changed in such a way that matching O 2 supply to O 2 demand does not work as well in older as in younger subjects. With regard to the O 2 demand component of the overall system, in vitro studies have shown that oxygen consumption (VO 2 ) remains constant until a critical partial pressure (P crit ) of O 2 (<1 mmHg) is reached. This knowledge was predicated on the assumption that the in vitro studies mimicked conditions in living tissue. More recently, however, in vivo studies have shown that VO 2 varies over a much wider range of O 2 partial pressure in the interstitial fluid (P ISF O 2 ). An intravital microscopic approach is being used to show that developmental changes in the O 2 transport system begin earlier than previously thought. Significant and rapid changes in the microvascular network of skeletal muscle have been observed during the first few weeks of postnatal development. Three different developmental groups of male Sprague‐Dawley rats (2, 4, and 6 months) were used to investigate early changes in the O 2 demand component of the transport system by measuring VO 2 and the P ISF O 2 dependence of VO 2 under resting conditions. VO 2 of the spinotrapezius muscle was measured with a quasi‐continuous, flash‐synchronized, rapidly pressurized airbag system to briefly arrest blood flow and determine the rate of decrease of oxygen tension (dPO 2 /dt) in the ISF bathing the skeletal muscle fibers. Changes in P ISF O 2 of the skeletal muscle were measured using phosphorescence quenching microscopy. To understand the PO 2 dependence of VO 2 , VO 2 data were plotted versus PO 2 and the results analyzed using a generalization of Michaelis‐Menten kinetics. This yielded information about both maximum VO 2 (V max ) and the PO 2 at half V max (P 50 ). Experiments were carried out on 16 animals with average weights (mean ± SEM) from 280 ± 10, 408 ± 17, to 454 ± 6 grams at 2 mo, 4 mo, and 6 mo, respectively. Average V max (mean ± SEM) was 138 ± 9, 148 ± 15, to 122 ± 6 nL O 2 /cm 3 ·s for 2 mo, 4 mo, and 6 mo, respectively. Between 2 mo and 6 mo, there was a downward trend with V max which was not significant. Average P 50 (mean ± SEM) was 11 ± 1, 15 ± 1, to 21 ± 1 mmHg for 2 mo, 4 mo, and 6 mo, respectively. There was a significant (p < 0.05) increase in P 50 from 2 mo to 6 mo which indicates that as the developmental age of the animal increases, there is an increased sensitivity of O 2 consumption to changes in P ISF O 2 . The findings are consistent with published data indicating that VO 2 depends on P ISF O 2 over a much wider physiological range than previously thought. It is clear that as the rat develops, it consumes less O 2 which may be ascribed to some combination of changes in the O 2 delivery system and mitochondrial function. Support or Funding Information Support from Department of Physiology and Biophysics This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .