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

2020 ◽  
Vol 129 (6) ◽  
pp. 1413-1421
Author(s):  
Leif Østergaard

The transport of oxygen between blood and tissue is limited by blood’s capillary transit time, understood as the time available for diffusion exchange before blood returns to the heart. If all capillaries contribute equally to tissue oxygenation at all times, this physical limitation would render vasodilation and increased blood flow insufficient means to meet increased metabolic demands in the heart, muscle, and other organs. In 1920, Danish physiologist August Krogh was awarded the Nobel Prize in Physiology or Medicine for his mathematical and quantitative, experimental demonstration of a solution to this conceptual problem: capillary recruitment, the active opening of previously closed capillaries to meet metabolic demands. Today, capillary recruitment is still mentioned in textbooks. When we suspect symptoms might represent hypoxia of a vascular origin, however, we search for relevant, flow-limiting conditions in our patients and rarely ascribe hypoxia or hypoxemia to short capillary transit times. This review describes how natural changes in capillary transit-time heterogeneity (CTH) and capillary hematocrit (HCT) across open capillaries during blood flow increases can account for a match of oxygen availability to metabolic demands in normal tissue. CTH and HCT depend on a number of factors: on blood properties, including plasma viscosity, the number, size, and deformability of blood cells, and blood cell interactions with capillary endothelium; on anatomical factors including glycocalyx, endothelial cells, basement membrane, and pericytes that affect the capillary diameter; and on any external compression. The review describes how risk factor- and disease-related changes in CTH and HCT interfere with flow-metabolism coupling and tissue oxygenation and discusses whether such capillary dysfunction contributes to vascular disease pathology.

1995 ◽  
Vol 79 (3) ◽  
pp. 1008-1026 ◽  
Author(s):  
D. R. Fine ◽  
D. Glasser ◽  
D. Hildebrandt ◽  
J. Esser ◽  
R. E. Lurie ◽  
...  

Hepatic function can be characterized by the activity/time curves obtained by imaging the aorta, spleen, and liver. Nonparametric deconvolution of the activity/time curves is clinically useful as a diagnostic tool in determining organ transit times and flow fractions. The use of this technique is limited, however, because of numerical and noise problems in performing deconvolution. Furthermore, the interaction of part of the tracer with the spleen and gastrointestinal tract, before it enters the liver, further obscures physiological information in the deconvolved liver curve. In this paper, a mathematical relationship is derived relating the liver activity/time curve to portal and hepatic behavior. The mathematical relationship is derived by using transit time spectrum/residence time density theory. Based on this theory, it is shown that the deconvolution of liver activity/time curves gives rise to a complex combination of splenic, gastrointestinal, and liver dependencies. An anatomically and physiologically plausible parametric model of the hepatic vascular system has been developed. This model is used in conjunction with experimental data to estimate portal, splenic, and hepatic physiological blood flow parameters for eight normal volunteers. These calculated parameters, which include the portal flow fraction, the splenic blood flow fraction, and blood transit times are shown to adequately correspond to published values. In particular, the model of the hepatic vascular system identifies the portal flow fraction as 0.752 +/- 0.022, the splenic blood flow fraction as 0.180 +/- 0.023, and the liver mean transit time as 13.4 +/- 1.71 s. The model has also been applied to two portal hypertensive patients. The variation in some of the model parameters is beyond normal limits and is consistent with the observed pathology.


2011 ◽  
Vol 32 (2) ◽  
pp. 264-277 ◽  
Author(s):  
Sune N Jespersen ◽  
Leif Østergaard

Normal brain function depends critically on moment-to-moment regulation of oxygen supply by the bloodstream to meet changing metabolic needs. Neurovascular coupling, a range of mechanisms that converge on arterioles to adjust local cerebral blood flow ( CBF), represents our current framework for understanding this regulation. We modeled the combined effects of CBF and capillary transit time heterogeneity (CTTH) on the maximum oxygen extraction fraction ( OEFmax) and metabolic rate of oxygen that can biophysically be supported, for a given tissue oxygen tension. Red blood cell velocity recordings in rat brain support close hemodynamic—metabolic coupling by means of CBF and CTTH across a range of physiological conditions. The CTTH reduction improves tissue oxygenation by counteracting inherent reductions in OEFmax as CBF increases, and seemingly secures sufficient oxygenation during episodes of hyperemia resulting from cortical activation or hypoxemia. In hypoperfusion and states of blocked CBF, both lower oxygen tension and CTTH may secure tissue oxygenation. Our model predicts that disturbed capillary flows may cause a condition of malignant CTTH, in which states of higher CBF display lower oxygen availability. We propose that conditions with altered capillary morphology, such as amyloid, diabetic or hypertensive microangiopathy, and ischemia—reperfusion, may disturb CTTH and thereby flow-metabolism coupling and cerebral oxygen metabolism.


1997 ◽  
Vol 83 (2) ◽  
pp. 543-549 ◽  
Author(s):  
Robert G. Presson ◽  
Thomas M. Todoran ◽  
Bracken J. De Witt ◽  
Ivan F. McMurtry ◽  
Wiltz W. Wagner

Presson, Robert G., Jr., Thomas M. Todoran, Bracken J. De Witt, Ivan F. McMurtry, and Wiltz W. Wagner, Jr.Capillary recruitment and transit time in the rat lung. J. Appl. Physiol. 83(2): 543–549, 1997.—Increasing pulmonary blood flow and the associated rise in capillary perfusion pressure cause capillary recruitment. The resulting increase in capillary volume limits the decrease in capillary transit time. We hypothesize that small species with relatively high resting metabolic rates are more likely to utilize a larger fraction of gas-exchange reserve at rest. Without reserve, we anticipate that capillary transit time will decrease rapidly as pulmonary blood flow rises. To test this hypothesis, we measured capillary recruitment and transit time in isolated rat lungs. As flow increased, transit time decreased, and capillaries were recruited. The decrease in transit time was limited by an increase in the homogeneity of the transit time distribution and an increased capillary volume due, in part, to recruitment. The recruitable capillaries, however, were nearly completely perfused at flow rates and pressures that were less than basal for the intact animal. This suggests that a limited reserve of recruitable capillaries in the lungs of species with high resting metabolic rates may contribute to their inability to raise O2 consumption manyfold above basal values.


1976 ◽  
Vol 51 (2) ◽  
pp. 151-159
Author(s):  
F. C. Reubi ◽  
C. Vorburger ◽  
Gertrud Pfeiffer ◽  
S. Golder

1. In nineteen patients with normal or diseased kidneys, renal blood flow, transit times and vascular volume were determined by means of an indicator-dilution method. Two different indicators, plasma-bound Indocyanine Green (IG) and 99mTc-labelled erythrocytes, were used simultaneously. 2. Comparison of the results indicates that IG slightly overestimates renal blood flow, appearance time, mean transit time and vascular volume, as the erythrocyte/IG ratios averaged 0·972, 0·903, 0·93 and 0·921 respectively. Overestimation of the mean transit time was less apparent when it was prolonged. In patients with reduced renal function, the average blood flow values obtained with the two indicators were in good agreement. 3. It is unlikely that axial streaming of erythrocytes accounts for their shorter mean transit time, because the individual erythrocyte/IG mean transit time ratios were independent of the rate of blood flow and the peripheral packed cell volume. 4. Since the erythrocyte/IG mean transit time ratios correlated significantly with the erythrocyte/IG ratios for appearance time and renal blood flow, the common mechanism leading to a depression of all erythrocyte/IG ratios is presumably extravascular circulation and delayed recovery of a small fraction of IG.


1981 ◽  
Vol 240 (2) ◽  
pp. H199-H208 ◽  
Author(s):  
C. R. Honig ◽  
C. L. Odoroff

Probability densities for red cell velocity (V) and capillary length (L) in dog gracilis muscles were computed from mean length and mean velocity assuming two-parameter gamma distributions [Honig, Feldstein, and Frierson, Am. J. Physiol. 233 (Heart Circ. Physiol. 2): H122-H129, 1977]. The distribution of capillary transit times (L/V) was obtained from the ratio of the two gamma distributions. The lower tails of transit time distributions were compared with times thought required for O2 release from capillaries. Results indicate the following. 1) Transit time exceeds O2 release time at rest in all capillaries, regardless of assumptions in the calculation. 2) Transit time appears long enough even in moderate exercise provided mean L is about 1,000 microns and release time is about 100 ms. 3) Capillary recruitment prevents a functional O2 shunt during work at one- to two-thirds maximum O2 uptake (VO2max). 4) Recruitment is insufficient to prevent O2 shunting during exercise to VO2max. 5) Quantitative analysis of O2 transport is severely limited by lack of information about a) microvascular geometry, b) the probability distributions of parameters, and c) the kinetics of O2 release from capillaries.


1970 ◽  
Vol 38 (6) ◽  
pp. 699-712 ◽  
Author(s):  
O. Munck ◽  
E. de Bono ◽  
I. H. Mills

1. The effect of infusion of isotonic saline on the circulation in the renal cortex in the dog was investigated by an external counting technique involving measurement of the transit times for 85Krypton and 131I-labelled albumin after rapid injection into the renal artery. 2. During saline infusion superficial renal cortical blood flow and overall cortical blood flow rose by 23 and 15%, respectively. There was a 6% rise in the ratio superficial cortical blood flow to overall cortical flow, which however, was not significant. 3. Resistance to flow through cortex decreased. 4. Mean transit time for plasma through cortex decreased from an average of 2·9 sec in the control period to 2·6 and 2·1 sec during saline infusion. 5. Renal cortical blood volume, as estimated from the cortical blood flow and the mean transit time for plasma, was virtually unchanged. 6. These studies indicate that the decrease in resistance to flow during acute isotonic saline infusion is probably caused by a dilatation of the resistance vessels only. No significant redistribution of blood flow in cortex takes place; this, however, does not exclude regional changes in glomerular filtration rate.


2011 ◽  
Vol 70 (suppl_1) ◽  
pp. ons65-ons74 ◽  
Author(s):  
Marcel A. Kamp ◽  
Philipp Slotty ◽  
Bernd Turowski ◽  
Nima Etminan ◽  
Hans-Jakob Steiger ◽  
...  

Abstract BACKGROUND: Intraoperative measurements of cerebral blood flow are of interest during vascular neurosurgery. Near-infrared indocyanine green (ICG) fluorescence angiography was introduced for visualizing vessel patency intraoperatively. However, quantitative information has not been available. OBJECTIVE: To report our experience with a microscope with an integrated dynamic ICG fluorescence analysis system supplying semiquantitative information on blood flow. METHODS: We recorded ICG fluorescence curves of cortex and cerebral vessels using software integrated into the surgical microscope (Flow 800 software; Zeiss Pentero) in 30 patients undergoing surgery for different pathologies. The following hemodynamic parameters were assessed: maximum intensity, rise time, time to peak, time to half-maximal fluorescence, cerebral blood flow index, and transit times from arteries to cortex. RESULTS: For patients without obvious perfusion deficit, maximum fluorescence intensity was 177.7 arbitrary intensity units (AIs; 5-mg ICG bolus), mean rise time was 5.2 seconds (range, 2.9-8.2 seconds; SD, 1.3 seconds), mean time to peak was 9.4 seconds (range, 4.9-15.2 seconds; SD, 2.5 seconds), mean cerebral blood flow index was 38.6 AI/s (range, 13.5-180.6 AI/s; SD, 36.9 seconds), and mean transit time was 1.5 seconds (range, 360 milliseconds-3 seconds; SD, 0.73 seconds). For 3 patients with impaired cerebral perfusion, time to peak, rise time, and transit time between arteries and cortex were markedly prolonged (>20, >9 , and >5 seconds). In single patients, the degree of perfusion impairment could be quantified by the cerebral blood flow index ratios between normal and ischemic tissue. Transit times also reflected blood flow perturbations in arteriovenous fistulas. CONCLUSION: Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.


2015 ◽  
Vol 08 (02) ◽  
pp. 1550025 ◽  
Author(s):  
Angelo Sassaroli ◽  
Jana Kainerstorfer ◽  
Sergio Fantini

A recently proposed analytical hemodynamic model1 [S. Fantini, NeuroImage85, 202–221 (2014)] is able to predict the changes of oxy, deoxy, and total hemoglobin concentrations (model outputs) given arbitrary changes in blood flow, blood volume, and rate of oxygen consumption (model inputs). One assumption of this model is that the capillary compartment is characterized by a single blood transit time. In this work, we have extended the original model by considering a distribution of capillary transit times and we have compared the outputs of both models (original and extended) for the case of sinusoidal input signals at different frequencies, which realizes the new technique of coherent hemodynamics spectroscopy (CHS). For the calculations with the original model, we have used the mean value of the distribution of capillary transit times considered in the extended model. We have found that, for distributions of capillary transit times having mean values around 1 s and a standard deviation less than about 45% of the mean value, the original and extended models yield the same CHS spectra (i.e., model outputs versus frequency of oscillation) within typical experimental errors. For wider capillary transit time distributions, the two models yield different CHS spectra. By assuming that Poiseuille's law is valid in the capillary compartment, we have related the distribution of capillary transit times to the distributions of capillary lengths and capillary speed of blood flow to calculate the average capillary and venous saturations. We have found that, for standard deviations of the capillary transit time distribution that are less than about 80% of the mean value, the average capillary saturation is always larger than the venous saturation. By contrast, the average capillary saturation may be less than the venous saturation for wider distributions of the capillary transit times.


1994 ◽  
Vol 76 (4) ◽  
pp. 1701-1711 ◽  
Author(s):  
R. G. Presson ◽  
C. C. Hanger ◽  
P. S. Godbey ◽  
J. A. Graham ◽  
T. C. Lloyd ◽  
...  

The complex morphology of the pulmonary capillary network causes capillary transit times to be dispersed about a mean. It is known that flow-induced decreases in mean capillary transit time are partially offset by capillary recruitment and distension, but the effect of these factors on the rest of the distribution of transit times is unknown. We have studied the relationship between blood flow, capillary recruitment, and the distribution of transit times in isolated canine lungs with videomicroscopy. Doubling baseline lobar blood flow recruited capillaries. All transit times in the distribution decreased, as did relative dispersion. Doubling flow again caused a further decrease in transit times, but neither capillary recruitment nor relative dispersion changed significantly. We conclude that capillary transit times become more homogeneous as lobar flow increases from low to intermediate levels. Further increases in flow across a fully recruited network are associated with decreases in transit times but not with more homogeneous capillary perfusion.


2020 ◽  
Vol 6 (3) ◽  
pp. 268-271
Author(s):  
Michael Reiß ◽  
Ady Naber ◽  
Werner Nahm

AbstractTransit times of a bolus through an organ can provide valuable information for researchers, technicians and clinicians. Therefore, an indicator is injected and the temporal propagation is monitored at two distinct locations. The transit time extracted from two indicator dilution curves can be used to calculate for example blood flow and thus provide the surgeon with important diagnostic information. However, the performance of methods to determine the transit time Δt cannot be assessed quantitatively due to the lack of a sufficient and trustworthy ground truth derived from in vivo measurements. Therefore, we propose a method to obtain an in silico generated dataset of differently subsampled indicator dilution curves with a ground truth of the transit time. This method allows variations on shape, sampling rate and noise while being accurate and easily configurable. COMSOL Multiphysics is used to simulate a laminar flow through a pipe containing blood analogue. The indicator is modelled as a rectangular function of concentration in a segment of the pipe. Afterwards, a flow is applied and the rectangular function will be diluted. Shape varying dilution curves are obtained by discrete-time measurement of the average dye concentration over different cross-sectional areas of the pipe. One dataset is obtained by duplicating one curve followed by subsampling, delaying and applying noise. Multiple indicator dilution curves were simulated, which are qualitatively matching in vivo measurements. The curves temporal resolution, delay and noise level can be chosen according to the requirements of the field of research. Various datasets, each containing two corresponding dilution curves with an existing ground truth transit time, are now available. With additional knowledge or assumptions regarding the detection-specific transfer function, realistic signal characteristics can be simulated. The accuracy of methods for the assessment of Δt can now be quantitatively compared and their sensitivity to noise evaluated.


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