Limitations of oxygen transport to the cell

Perhaps the major points to be made from this review are the following: 1. Transport of O2 from the environment to the mitochondrion is accomplished in a well-described but not yet well-understood sequence of diffusive and convective steps that are highly interactive and thus integrative in their outcome. 2. Thus, under conditions of O2-supply limitation of VO2max in strenuous exercise in health, all transport steps affect the value of VO2max reached, but the sensitivity of VO2max (to changes in any step) is not the same for each step, and moreover, will vary with the quantitative conditions. It is time to abandon the very concept of a single limiting factor to VO2max. 3. O2 supply limitation of VO2 is seen under two very different conditions that in fact are at the opposite ends of the spectrum of metabolic scope: VO2max in strenuous exercise in health and basal VO2 in severe disease. Analysis of the latter using lessons learned from the former may be valuable. 4. We are currently greatly limited in our understanding of supply limitation in disease, mostly because of unavailability of methods to assess organ-specific cellular metabolism and its relation to O2 supply in patients, essentially noninvasively--a research direction that needs much support.