Capillary-mitochondrial Oxygen Transport in Muscle: Paradigm Shifts, 2023, David C Poole

Abstract
During maximal exercise healthy humans increase their oxygen uptake (V̇O2) 10 to 20-fold that measured at rest to as much as 6 L/min. At the molecular level the numbers are staggering: Each minute the exercising O2 transport system - lungs, cardiovascular and active muscles – must uptake, transport and utilize some 161 sextillion (1021) O2 molecules. When specifically recruited the exercising quadriceps muscles can increase their blood flow over 100-fold resting values and transport 17 sextillion O2 molecules per kilogram per minute from microcirculation (capillaries) to mitochondria powering their cellular energetics.

Within these muscles, the capillary network constitutes a prodigious blood-tissue interface essential to exchange the O2, carbon dioxide, substrates and signaling molecules requisite for muscle function and health.

In disease, microcirculatory dysfunction underlies the pathophysiology of heart failure, diabetes, hypertension, pulmonary disease, and sepsis, as well as stroke and senile dementia. Effective therapeutic countermeasure design demands knowledge of microvascular/capillary function in health to recognize and combat pathological dysfunction.

Dated concepts of skeletal muscle capillary (from the Latin capillus meaning ‘hair’) function prevail despite rigorous data-supported contemporary models; hindering progress in the field for future and current students, researchers and clinicians. Following closely the 100th anniversary of August Krogh's 1920 Nobel Prize for capillary function this Evidence Review presents an anatomical and physiological development of this dynamic field: Constructing a scientifically defensible platform for our current understanding of microcirculatory physiological function in supporting blood-mitochondrial O2 transport.

New developments highlighted include: 1. Putative roles of aquaporin and rhesus channels on the RBCs in determining tissue oxygen diffusing capacity. 2. Recent discoveries and theories regarding intramyocyte oxygen transport. 3. Developing a comprehensive capillary functional model for skeletal muscle to help explain O2 delivery-to-V̇O2 matching. Unique to this endeavor is the incorporation of kinetics analysis to discriminate putative control mechanisms from collateral or pathological phenomena.

https://academic.oup.com/function/advance-article/doi/10.1093/function/zqad013/7079133?login=false