Erythrocyte flux in capillary networks during maturation: implications for oxygen delivery

Abstract

Erythrocyte (RBC) flow variables were measured with videomicroscopy in hamster cremaster muscle capillary networks. Capillary networks consist of subgroups, termed modules, with architectural characteristics that are invariant with maturation [B. R. Berg and I. H. Sarelius. Am. J. Physiol, 268 (Heart Circ. Physiol. 37): H1215-H1222, 1995]. RBC flux in modules decreased from 82.0 +/- 4.3 (SE) cells/s at 51 days of age to 59.5 +/- 7.5 and 27.5 +/- 2.8 cells/s at 65 and 79 days of age, respectively. Mean cell velocity at 51 days (385 +/- 10 microns/s) was higher than at 65 or 79 days (285 +/- 15 and 241 +/- 12 microns/s, respectively). Cell content (number of cells per unit length) decreased later, between 65 and 79 days (from 0.21 +/- 0.01 and 0.23 +/- 0.02 cells/micron at 51 and 65 days, respectively, to 0.12 +/- 0.01 cells/micron at 79 days). These temporal differences in the decrease in cell velocity and cell content suggest different regulatory mechanisms. The capacity of capillary networks to deliver oxygen was modeled by using the calculated mean PO2 at the capillary wall to indicate the capacity to delivery oxygen. During maturation, the mean capillary wall PO2 remained unchanged (15.5 +/- 1.2 and 11.4 +/- 2.7 Torr in maximal dilation and 24.5 +/- 1.4 and 22.8 +/- 2.4 Torr at rest at 51 and 79 days, respectively). Thus, despite changes in RBC flow variables with maturation, the capacity for networks to deliver oxygen remains constant.

Primary Role of Functional Ischemia, Quantitative Evidence for the Two-Hit Mechanism, and Phosphodiesterase-5 Inhibitor Therapy in Mouse Muscular Dystrophy

“…The validity of our labeling method is thus assured by the consistency with the previous studies reporting RBC flux at venules (12–39 µm in diameter, presumably secondary to tertiary venules) of c.a. 100,000 per minute in mice [25], and resting capillary flux of 1,800 or 1200–2000 per minute in rats [26] or in hamsters [27] (note that one primary arteriole feeds several capillaries and dozens of capillaries feed into secondary venules).…”

Skeletal Muscle Circulation

“…Arterioles enter the perimysium and travel perpendicular the muscle fiber axis until giving rise to terminal branches that penetrate the perimysium and immediately branch into numerous capillaries that are embedded in the endomysium and travel parallel to the muscle fiber ( Figure 1). This non-uniform distribution of capillaries around myofibrils, coupled with the fact that the circumference of each muscle fiber is quite variable, indicates that oxygen is non-homogeneously distributed to skeletal muscles, even under conditions of maximal capillary recruitment [47,48,584]. Thus, the group of capillaries perfused by a terminal arteriole has been termed the microvascular unit, which represents the smallest functional unit for blood flow regulation in skeletal muscle ( Figure 1) [32,58,602].…”

“…It is important to recognize that opening capillaries to flow not only increases the surface area available for exchange but also decreases diffusion distance over which oxygen must flux in moving from the bloodstream to the muscle fibers [47,48,207]. From the geometric organization of skeletal muscle capillaries, it has become apparent that surface area increases in direct proportion to the number of open capillaries (n ), while diffusion distance is inversely proportional to the square root of n [207].…”

“…However, capillary perfusion is not controlled on a single capillary basis, but rather occurs by recruitment as groupings of capillaries (microvascular units, networks, or modules) at the initiation of muscular activity [105,116,199,265,581,584,665]. It appears that capillary blood flow, erythrocyte distribution, and red cell concentration are coordinated within and among these microvascular units to equalize oxygen supply [47,48,583]. This coordination is facilitated by conducted (propagated) vasodilator responses, which also function to minimize perfusion heterogeneity by reducing the potential for more dilated arterioles to steal flow from less dilated microvessels [606][607][608].…”

Increased myogenic responsiveness of skeletal muscle arterioles with juvenile growth

“…In resting muscle, oxygen delivery and oxygen consumption are tightly linked throughout postnatal growth, with no age-related variations in the steadystate level of tissue oxygenation (41). However, measurements made in contracting muscle indicate that there is a marked change in the dynamic coupling between blood flow and metabolic activity over this rapid growth period (7,41). Although it is not clear whether this is related to the changing metabolic demands that accompany muscle growth (24,27,29), this change in dynamic coupling would most likely involve a corresponding shift in the gain of local blood flow control mechanisms.…”