Blood flow, capillary transit times, and tissue oxygenation: the centennial of capillary recruitment

Abstract

The transport of oxygen between blood and tissue is limited by blood's capillary transit time: The time available for diffusion exchange before blood returns to the heart. If all capillaries had identical extraction properties, this physical limitation would render vasodilation and increased blood flow insufficient means to meet increased metabolic demands in the brain, heart, and other organs. In 1920, Danish physiologist August Krogh was awarded the Nobel Prize in Physiology or Medicine for his solution to this conceptual problem: Capillary recruitment, the opening of previously closed capillaries. Today, capillary recruitment mainly lives on i textbooks. When we suspect symptoms might represent hypoxia of a vascular origin, we search for relevant, flow-limiting conditions in our patients and rarely ascribe hypoxia or hypoxemia to short capillary transit times. This Primer describes how natural changes in capillary transit-time heterogeneity (CTH) and capillary hematocrit (across open capillaries) during increases in blood flow can match oxygen availability to metabolic demands in normal tissue, and how the assumption of negligible CTH lead us to underestimate capillaries' role in tissue oxygenation. CTH and capillary hematocrit depend on plasma viscosity, on the number, size and deformability of blood cells and their interactions with capillary endothelium, on the glycocalyx, endothelial cells, basement membrane, and pericytes that define the capillary lumen, and on any external compression. The Primer describes how risk factor- and disease-related changes in CTH and capillary hematocrit interfere with flow-metabolism coupling and tissue oxygenation, and discusses whether such capillary dysfunction contributes to vascular disease pathology.

SARS CoV‐2 related microvascular damage and symptoms during and after COVID‐19: Consequences of capillary transit‐time changes, tissue hypoxia and inflammation

“…The critical transition at CTH c is therefore expected to be presaged by a gradual attenuation of vasodilator responses before this threshold is reached, as the accompanying blood flow increases critically shorten transit times. This property has been linked to endothelial dysfunction (attenuated flow responses to endothelial‐dependent vasodilators) characteristic of cardiovascular risk factors, and the subsequent increase in vascular resistance and vascular wall remodeling associated with hypertension (Østergaard, 2020).…”

“…While we are familiar with the pathophysiology, symptoms, diagnostic findings, and management of large vessel occlusions (e.g., acute stroke, coronary occlusion, pulmonary embolism, deep venous thrombosis), the consequences of microcirculatory disturbances, for example, the narrowing or occlusion of individual capillaries, remain unclear (Ackermann et al, 2020; Fox et al, 2020; Varga et al, 2020). This review addresses this knowledge gap (Østergaard, 2020).…”

“…Therefore, blood's uptake of oxygen in the lungs, and the uptake of oxygen by tissue, not only depend on blood flow , but also on bloods microscopic distribution across the capillary bed (Angleys & Østergaard, 2020; Hsia et al, 1999; Jespersen & Østergaard, 2012; Østergaard, 2020). Biophysically, the redistribution of blood among open capillaries can account for the puzzling increase in oxygen PS observed as blood flow increases through most organs, without the need to invoke classical “capillary recruitment” (the active opening of previously closed capillaries), which has now been ruled out in most organs (Østergaard, 2020; Poole et al, 2020). This review focuses on the effects of break ‐ downs in the factors that ensure the crucial, parallel increase in PS and blood flow, after biophysical models have predicted that capillary occlusions and severe capillary flow disturbances can limit tissue oxygenation to the same extent as symptomatic reductions in blood flow (ischemia) in brain, heart, and kidneys (Østergaard et al, 2013, 2014, 2015).…”

“…Our current vascular disease paradigm focuses on blood flow ‐ limiting conditions on the one hand, and symptoms of hypoxia and hypoxic tissue injury, on the other. Blood's capillary transit time, however, determines the time availability for blood‐tissue oxygen exchange, and any deviations from a homogenous distribution of blood across the capillary bed therefore reduce the capillary bed's functional capillary permeability surface area product (PS) for oxygen transport (Jespersen & Østergaard, 2012; Østergaard, 2020). Therefore, blood's uptake of oxygen in the lungs, and the uptake of oxygen by tissue, not only depend on blood flow , but also on bloods microscopic distribution across the capillary bed (Angleys & Østergaard, 2020; Hsia et al, 1999; Jespersen & Østergaard, 2012; Østergaard, 2020).…”

“…Blood's capillary transit time, however, determines the time availability for blood‐tissue oxygen exchange, and any deviations from a homogenous distribution of blood across the capillary bed therefore reduce the capillary bed's functional capillary permeability surface area product (PS) for oxygen transport (Jespersen & Østergaard, 2012; Østergaard, 2020). Therefore, blood's uptake of oxygen in the lungs, and the uptake of oxygen by tissue, not only depend on blood flow , but also on bloods microscopic distribution across the capillary bed (Angleys & Østergaard, 2020; Hsia et al, 1999; Jespersen & Østergaard, 2012; Østergaard, 2020). Biophysically, the redistribution of blood among open capillaries can account for the puzzling increase in oxygen PS observed as blood flow increases through most organs, without the need to invoke classical “capillary recruitment” (the active opening of previously closed capillaries), which has now been ruled out in most organs (Østergaard, 2020; Poole et al, 2020).…”