Impact of early mammalian development on the response of the O2 transport system to muscle contraction

Abstract

A continuous supply of O2 to the cells in the body is necessary to maintain normal physiological function and the microcirculation is especially important in this matter as it is the site of O2 exchange. Under conditions of active/functional hyperemia following muscle contractions, the O2 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 O2 transport and regulatory systems are changed in such a way that matching O2 supply to O2 demand does not work as well in older as in younger subjects. An intravital microscopic approach is being used to show that developmental changes in the O2 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. Four different developmental groups of male Sprague‐Dawley rats (8, 16, 24, and 52 weeks) are used to investigate changes in the O2 demand component of the transport system by measuring oxygen consumption (VO2) and the PISFO2 dependence of VO2 under conditions of rest and contraction. VO2 was measured with a quasi‐continuous, flash‐synchronized, rapidly pressurizing airbag system to briefly arrest flow and determine the rate of change in oxygen tension (dPO2/dt). Changes in the O2 supply component are investigated by measuring capillary and interstitial fluid PO2 (PcapO2 and PISFO2 respectively, using phosphorescence quenching microscopy) and surface area available for O2 exchange (i.e., capillary density). Preliminary experiments were carried out on six animals that ranged from 8 w to 20 w in age with an average weight of 331 ± 35 g. Average baseline VO2 for the 8 w group was 307 ± 26 nL O2/cm3·s (n = 6), average baseline VO2 for the 16 w group was 287 ± 31 nL O2/cm3·s (n = 6), and average baseline VO2 for those in the 24 w group was 264 ± 12 nL O2/cm3·s (n = 6). Average baseline PISFO2 for the 8 w group was 68 ± 3 mmHg (n = 6), average baseline PISFO2 for the 16 w group was 74 ± 4 mmHg (n = 6), and average baseline PISFO2 for the 24 w group was 68 ± 3 mmHg (n = 6). The observed decreases in tissue VO2 are consistent with literature showing that whole body VO2 decreases from 499, 396, to 345 nL O2/cm3·s at 8 w, 16 w, and 24 w, respectively. However, it is still unclear how well matched O2 supply and demand are. As O2 demand increases by increasing muscle contraction, O2 supply should also increase to match it and PISFO2 is at least one element that links the two components of the transport system which requires further investigation.