Optimal hematocrit theory during activity in the bullfrog (Rana catesbeiana).

1. There is an exponential relationship between blood viscosity (cP) and hematocrit (%) for the bullfrog; eta = 1.81 e0.033Hct. The in vitro optimal hematocrit calculated for blood flow through tubes, from this relationship for bullfrog blood, is 30%. 2. Amphibian blood is a non-Newtonian fluid with viscosity dependent on shear rate. It has a finite yield shear stress of about 1.5 dynes cm-2. 3. Hematocrit of bullfrogs was increased from 27% (control) to 57% by isovolemic erythrocythemia (constant volume blood-doping). There was a slight increase in systolic, diastolic and venous blood pressure with elevated hematocrit. 4. Systemic arch blood flow rate was inversely related to blood viscosity for erythrocythemic bullfrogs. The decrease in systemic arch blood flow at high hematocrits was due primarily to reduced pulse volume rather than reduced heart rate. 5. Systemic arch blood flow, when standardised between individuals, was inversely related to blood viscosity; Qbl = 0.185 + 3.73 eta -1. This relationship was significantly different from that predicted by the Poiseuille-Hagen flow formula. The in vivo optimal hematocrit calculated from this relationship was 41%. 6. Optimal hematocrit theory appears to be generally applicable for Rana catesbeiana in vitro and in vivo. Most individuals had an in vivo optimal hematocrit, but the absence of a clear optimal hematocrit for some individuals could reflect methodological variability, or in vivo physiological compensation for the increased blood viscosity at high hematocrit.     

Blood flow oscillations at a frequency of about 0.1 Hz in skin microvessels do not reflect the sympathetic regulation of their tone

Wavelet analysis of blood flow oscillations recorded with laser Doppler flowmetry in finger glabrous skin microvessels was carried out in 82 subjects with different variations in the syndromes of hand and foot sympathectomy and denervation. As distinct from the 0.02–0.046-Hz (about 0.03–0.04 Hz) blood flow oscillations in skin microvessels of sympathetic thermoregulatory origin, no relationship was found between the presence of 0.07–0.015 Hz (about 0.1 Hz) vasomotions in the wavelet spectrum and intactness of sympathetic innervation in the tissue region. The use of the myogenic band oscillation parameters, in particular, the amplitudes of vasomotions, for assessing the state of sympathetic thermoregulatory innervation determining the neurogenic tone of skin microvessels is not physiologically correct. The influence of local environmental factors on the vasomotion parameters confirms their local origin. The local perfusion pressure value significantly influenced the amplitude but not the frequency of vasomotions. The amplitude dominance of vasomotions was observed upon a decrease in perfusion pressure, whereas a marked increase in perfusion pressure or venous congestion resulted in a sharp depression of their amplitudes. Under the sympathectomy conditions, the oscillatory dynamic component of the arteriolar myogenic tone in the glabrous skin of the extremity acral zones is involved in the blood flow’s autoregulation. The presence of fine sensory fibers is necessary to carry out the dynamic autoregulation of the blood flow. Sensory nonmyelinated fibers and the trophic neuropeptides secreted by them not only initiate independent oscillations in the low-frequency (0.047–0.069 Hz) myogenic band, but also contribute to the normalized amplitudes of vasomotions being increased. At the same time, no appreciable influence of the sympathetic vasomotor activity and the corresponding influence of catecholamines on the amplitude and frequency of vasomotions was observed.     

Blood flow switching among pulmonary capillaries is decreased during high hematocrit.

Pulmonary capillary perfusion within a single alveolar wall continually switches among segments, even when large-vessel hemodynamics are constant. The mechanism is unknown. We hypothesize that the continually varying size of plasma gaps between individual red blood cells affects the likelihood of capillary segment closure and the probability of cells changing directions at the next capillary junction. We assumed that an increase in hematocrit would decrease the average distance between red blood cells, thereby decreasing the switching at each capillary junction. To test this idea, we observed 26 individual alveolar capillary networks by using videomicroscopy of excised canine lung lobes that were perfused first at normal hematocrit (31-43%) and then at increased hematocrit (51-62%). The number of switches decreased by 38% during increased hematocrit (P < 0.01). These results support the idea that a substantial part of flow switching among pulmonary capillaries is caused by the particulate nature of blood passing through a complex network of tubes with continuously varying hematocrit.     

A semi-empirical model for flow of blood and other particulate suspensions through narrow tubes

A semi-empirical model applicable to the flow of blood and other particulate suspensions through narrow tubes has been developed. It envisages a central core of blood surrounded by a wall layer of reduced hematocrit. With the help of this model the wall layer thickness and extent of plug flow may be calculated using pressure drop, flow rate and hematocrit reduction data. It has been found from the available data in the literature that for a given sample of blood the extent of plug flow increases with decreasing tube diameter. Also for a flow through a given tube it increases with hematocrit. The wall layer thickness is found to decrease with increase in blood hematocrit. A comparison between the results of rigid particulate suspensions and blood reveals that the thicker wall layer and smaller plug flow radius in the case of blood may be attributed to the deformability of the erythrocytes.     

Rheologic changes with streptokinase--experimental studies]

In dogs with artificial stenosis of the femoral artery application of 96 000 IU Awelysin/kg initially and subsequent infusion of 1200 IU/kg/min caused an increase of the blood flow below the stenosis. The improvement in blood flow is attributed to the decrease in fibrinogen and to the increase in fibrinogen degradation products.     

A fluid--structure interaction finite element analysis of pulsatile blood flow through a compliant stenotic artery.

A new model is used to analyze the fully coupled problem of pulsatile blood flow through a compliant, axisymmetric stenotic artery using the finite element method. The model uses large displacement and large strain theory for the solid, and the full Navier-Stokes equations for the fluid. The effect of increasing area reduction on fluid dynamic and structural stresses is presented. Results show that pressure drop, peak wall shear stress, and maximum principal stress in the lesion all increase dramatically as the area reduction in the stenosis is increased from 51 to 89 percent. Further reductions in stenosis cross-sectional area, however, produce relatively little additional change in these parameters due to a concomitant reduction in flow rate caused by the losses in the constriction. Inner wall hoop stretch amplitude just distal to the stenosis also increases with increasing stenosis severity, as downstream pressures are reduced to a physiological minimum. The contraction of the artery distal to the stenosis generates a significant compressive stress on the downstream shoulder of the lesion. Dynamic narrowing of the stenosis is also seen, further augmenting area constriction at times of peak flow. Pressure drop results are found to compare well to an experimentally based theoretical curve, despite the assumption of laminar flow.     

迷走神经与乙酰胆碱对缩窄的犬冠状动脉节段阻力的影响

在麻醉开胸犬,用电起搏维持心率恒定,研究了电刺激颈迷走神经(VNS)及冠状动脉内注入乙酰胆碱(ACh)对缩窄的冠状动脉的节段阻力及血流量的影响。在左旋支主干造成不同程度的冠状动脉缩窄。分别测定左旋支血流量(CBF_(cx))、主动脉压和主旋支远端冠状动脉压,记录心电图。实验发现,在冠状动脉临界狭窄和重度狭窄时,VNS 或冠脉给ACh 引起心外膜大冠状动脉阻力及冠状动脉主旋支总阻力增大,CBF_(cx)减少;随着缩窄程度加重,这些改变也愈明显,然而,心肌内小冠状动脉阻力却无显著改变。     

Catecholamines and regional hemodynamics during isovolemic hemodilution in anesthetized pigs.

The effects of stepwise isovolemic hemodilution on systemic and regional hemodynamics, oxygen flux, and circulating catecholamines were studied in six pigs anesthetized with midazolam and fentanyl. Reduction of the hematocrit from 28 to 9% resulted in doubling of the cardiac output, mainly due to an increase in stroke volume. Regional blood flows, measured using the radioactive microsphere technique, showed an increase in blood flow to all organs except liver (hepatic artery fraction) and adrenals, with a redistribution of cardiac output in favor of heart and brain (increase in blood flow 420 and 170%, respectively). Oxygen flux to most organs did not decrease until hematocrit decreased to 9%, while total body oxygen consumption was well maintained. Left ventricular oxygen consumption increased, but because left ventricular blood flow also increased, left ventricular extraction ratio did not increase. Circulating catecholamines did not play any role in these regulatory mechanisms.     

Numerical solution of unsteady blood flow through an indented tube with atherosclerosis

The unsteady blood flow through an indented tube with atherosclerosis in the presence of mild stenosis has been studied numerically by finite difference method. The effects of hematocrit, frequency parameter, height of stenosis, parameter determining the shape of the constriction on velocity field, volumetric flow rate, pressure gradient of the fluid in stenotic region and wall shear stress at the surface of stenosis are obtained and shown graphically.     

Rheology of embryonic avian blood

Shear stress, a mechanical force created by blood flow, is known to affect the developing cardiovascular system. Shear stress is a function of both shear rate and viscosity. While established techniques for measuring shear rate in embryos have been developed, the viscosity of embryonic blood has never been known but always assumed to be like adult blood. Blood is a non-Newtonian fluid, where the relationship between shear rate and shear stress is nonlinear. In this work, we analyzed the non-Newtonian behavior of embryonic chicken blood using a microviscometer and present the apparent viscosity at different hematocrits, different shear rates, and at different stages during development from 4 days (Hamburger-Hamilton stage 22) to 8 days (about Hamburger-Hamilton stage 34) of incubation. We chose the chicken embryo since it has become a common animal model for studying hemodynamics in the developing cardiovascular system. We found that the hematocrit increases with the stage of development. The viscosity of embryonic avian blood in all developmental stages studied was shear rate dependent and behaved in a non-Newtonian manner similar to that of adult blood. The range of shear rates and hematocrits at which non-Newtonian behavior was observed is, however, outside the physiological range for the larger vessels of the embryo. Under low shear stress conditions, the spherical nucleated blood cells that make up embryonic blood formed into small aggregates of cells. We found that the apparent blood viscosity decreases at a given hematocrit during embryonic development, not due to changes in protein composition of the plasma but possibly due to the changes in cellular composition of embryonic blood. This decrease in apparent viscosity was only visible at high hematocrit. At physiological values of hematocrit, embryonic blood viscosity did not change significantly with the stage of development.     

Assessment of the changes in regulatory systems of human's skin blood flow during local heating

The mechanisms of thermal regulation of skin blood flow during local heating to 35, 40 and 45 'C have been studied by the method of laser Doppler flowmetry in healthy volunteers. To estimate the state of microvascular bed the continuous wavelet-transform spectral analysis has been used. The amplitudes of fluxmotions in the range of blood flow active modulation significantly increase during local heating to 35 degrees C. The amplitudes of blood flow oscillations in the ranges of cardiorhythm and respiratory rhythm increase during local heating to 40 degrees C. The high amplitude oscillations in the range of myogenic activity are maintained. The amplitude of oscillations in the range of endothelial activity distinctly decreases and the oscillations in the range of neurogenic activity are inhibited. Local heating to 45 degrees C results in a significant decreasing of the oscillation amplitudes in the range of myogenic activity, and the amplitudes of cardio- and respiratory spectral components amount to their peak values among the temperatures of local heating under study.     

The "black hole" phenomenon in ultrasonic backscattering measurement under pulsatile flow with porcine whole blood in a rigid tube

The "black hole" phenomenon was further investigated with porcine whole blood under pulsatile flow conditions in a straight rigid tube 120 cm long and of 0.95 cm diameter. A modified Aloka 280 commercial scanner with a 7.5 MHz linear array was used to collect the radio frequency (RF) signal of backscattering echoes from the blood inside the tube. The transducer was located downstream from the entrance and parallel to the longitudinal direction of the tube. The experimental results showed that higher hematocrits enhanced the black hole phenomenon, leading to a more apparent and larger diameter black hole. The black hole was not apparent at hematocrits below 23%. The highest hematocrit used in the experiment was 60%. Beat rates of 20, 40 and 60 beats per minute (bpm) were used, and the black hole became weaker in amplitude and smaller in diameter when the peak flow velocity was increased at each beat rate. These results are consistent with the suggestion in previous work that the black hole arises from insufficient aggregation of red blood cells (RBCs) at the center of the tube because of the low shear rate. At 20 and 40 bpm, the peak flow velocity ranges were 10 approximately 25 cm/s and 18 approximately 27 cm/s, respectively. The black hole was very clear at the minimal peak flow velocity but almost disappeared at the maximal velocities for each beat rate. At 60 bpm, experiments were only performed at one peak flow velocity of 31 cm/s and the black hole was clear. The results showed that the black hole was more pronounced at higher beat rates when the peak velocity was the same. This phenomenon cannot be explained by previous hypotheses. Acceleration seems to be the only flow parameter that varies at different beat rates when peak velocities are the same. Therefore, the influence of acceleration on the structural organization and orientation of RBC rouleaux might be another factor involved in the formation of the black hole in addition to the shear rate. As the entrance length was changed from 110 to 15 diameters (D) in seven steps at the hematocrit of 60%, it was found that a position farther downstream yielded a black hole with a greater contrast relative to the surrounding region, while the backscattering power at the central hypoechoic zone did not increase with increasing entrance length.     

Effect of hypovolemia on forearm vascular resistance control during exercise in the heat.

To determine the influence of hypovolemia on the control of forearm vascular resistance (FVR) during dynamic exercise, we studied five physically active men during 60 min of supine cycle ergometer exercise bouts at 35 degrees C in control (normovolemic) and hypovolemic conditions. Hypovolemia was achieved by 3 days of diuretic administration and resulted in an average decrease in plasma volume of 15.9%. Relative to normovolemia, hypovolemia caused an attenuation of the progressive rise in forearm blood flow (P less than 0.05) and an increase in heart rate (P less than 0.05) during exercise. Because mean arterial blood pressure during hypovolemic exercise was well maintained, the attenuation of forearm blood flow was due entirely to a relative increase in FVR. At the onset of dynamic exercise, FVR was increased significantly in control and hypovolemic conditions by 13.2 and 27.1 units, respectively. The increase in FVR was significantly different between control and hypovolemic conditions as well. We attributed the increased vasoconstrictor bias during hypovolemia to cardiopulmonary baroreceptor unloading and/or an increased sensitivity to cardiopulmonary baroreceptor unloading. We concluded that reduced blood flow to the periphery during exercise in the hypovolemic condition was caused entirely by an increase in vascular resistance, thereby preserving arterial blood pressure and adequate perfusion to the organs requiring increased flow.     

Mechanical behavior of the erythrocyte in microvessel stenosis

The passage of red blood cells (RBCs) through capillaries is essential for human blood microcirculation. This study used a moving mesh technology that incorporated leader-follower pairs to simulate the fluid-structure and structure-structure interactions between the RBC and a microvessel stenosis. The numerical model consisted of plasma, cytoplasm, the erythrocyte membrane, and the microvessel stenosis. Computational results showed that the rheology of the RBC is affected by the Reynolds number of the plasma flow as well as the surface-to-volume ratio of the erythrocyte. At a constant inlet flow rate, an increased plasma viscosity will improve the transit of the RBC through the microvessel stenosis. For the above reasons, we consider that the decreased hemorheology in microvessels in a pathological state may primarily be attributed to an increase in the number of white blood cells. This leads to the aggregation of RBCs and a change in the blood flow structure. The present fundamental study of hemorheology aimed at providing theoretical guidelines for clinical hemorheology.     

Some factors affecting tissue Po2 in the carotid body.

In the carotid body (CB) of the anesthetized cat tissue Po2 (Pto2) measured with a micro O2 electrode averaged about 65 mmHg at normal arterial pressure (mean = 96 mmHg). Pto2 correlated significantly with the hematocrit of the arterial blood but not with % saturation. When arterial pressure was reduced (mean = 58 mmHg) by bleeding Pto2 fell significantly. Phentolamine injection (1 mg/kg iv) at the reduced pressure caused Pto2 to rise significantly. At normal arterial pressure blowing moistened O2 over the CB did not affect Pto2 if the electrode tip was about 90 mum into the CB. At a reduced pressure (and blood flow) the sensitive depth increased to about 301 mum, and to about 600 mum when flow was stopped. We concluded that a) the increased chemoceptor discharge usually seen with hemorrhage is due to reduced Pto2; b) the reduction in Pto2 is probably due to reduced blood flow which is, in turn, caused partly, at least, by sympathetic nervous system activity; c) O2 content, rather than Po2, may determine chemoreceptor discharge rate; and d) there are no barriers in the CB which are impermeable to O2.     

Ultrasonic evaluation of erythrocyte aggregation dynamics

The dynamics of aggregation and disaggregation of blood of varying hematocrit in oscillatory flow in a distensible horizontal tube was determined by measuring the developing echo intensity of the blood samples with a 10 MHz B-mode ultrasonic scanner. Early aggregation could be detected within 10 sec. of stoppage of flow. The rate of echo intensity buildup and thus, presumably the rate of aggregation when flow was stopped was inversely related to hematocrit, as was the rate of echo intensity reduction when flow was resumed. Polycythemic blood of 60% hematocrit showed no echo intensity increase over 5 min. Increasing the shear stress when flow was resumed resulted in rapid decreases in aggregation. In all cases, disaggregation following flow resumption was faster than aggregation following flow stoppage.     

Effect of hematocrit on wall shear rate in oscillatory flow: do the elastic properties of blood play a role?

Porcine blood was used to examine the relationship between hematocrit levels and wall shear rate patterns in straight and curved artery models under fixed oscillatory flow conditions characteristic of larger arteries. It is demonstrated that porcine blood models both the viscous and elastic components of the 2 Hz complex viscosity of human blood quite accurately over a broad range of shear rates (1-1000 s-1) and hematocrits (20%-80%). For a fixed oscillatory flow waveform (Poiseuille peak shear rate = 168 s-1; mean shear rate 84 s-1), increases in hematocrit produced a decrease in the peak wall shear rate in both the straight and curved artery models and a corresponding decrease in wall shear rate reversal on the inside wall of the curved artery model. The same trends were also observed for oscillatory flows of aqueous glycerin solutions of increasing viscosity in the range of viscosity of the blood samples tested. Aqueous glycerin solutions produced wall shear rate waveforms of the same magnitude and shape as the porcine blood. This indicates that variations in the shear rate, and therefore the shear stress, were caused primarily by changes in the viscous and not the elastic properties of blood. The results suggest that simple Newtonian fluids may be sufficient for in vitro determination of the first order effects to be expected of human blood flow in large vessels having complex geometries and shear rates in or above the range of the present study.     

The influence of the sympathetic innervation on the skin microvascular tone and blood flow oscillations

The influence of the sympathetic innervation on the tone of resistive vessels and blood flow oscillations was studied using laser Doppler flowmetry and skin thermography in 18 healthy subjects (before and after reflex cold and heat tests and local thermal testing), 42 patients with denervation syndromes caused by median nerve damage, and 10 patients with an acute stage of aseptic inflammation after radius fracture. The blood flow oscillations in the range of neurogenic sympathetic influences (0.02–0.052 Hz) supported by low-frequency sympathetic rhythms are an essential component of neurovascular interrelations. The importance of these oscillations is determined by their contribution to an increase in tissue perfusion owing to a decrease in the peripheral resistance and also by the leveling of drastic changes in blood flow and stabilization of microhemodynamics upon pronounced changes in the stationary tone. The high-and low-frequency (tonic and oscillatory, respectively) sympathetic rhythmic activities are expressed in two ways: (1) a synchronous increase or decrease in their amplitudes and (2) frequency dominance. The reactivity of the vessel smooth muscles is an important factor in maintaining the blood flow oscillations. Denervation decreases the oscillation amplitude in the neurogenic range. Under the conditions of local “inflammatory sympatholysis,” reflex tonic effects, rather than oscillatory ones, of the sympathetic impulses are mainly suppressed. An isolated evaluation of the blood flow oscillations in the neurogenic sympathetic range cannot be a measure of sympathetic activity. In studies on its functional state and evaluation of the neurogenic tone (NT) of resistive vessels, it is necessary to take into account the parameters of both stationary and oscillatory components of the NT.     

Cardiac edema in dogs: distribution of renal blood flow and glomerular filtrate.

The injection of Freund's adjuvant into the pericardial sac of 29 dogs resulted in chronic pericardial tamponade with persistent sodium retention. Micropuncture, clearance, and radioactive microsphere experiments were initiated 6--13 days after pericardial injection and 60 min after pericardiocentesis. Pericardiocentesis increased sodium excretion (from 12.2 to 41.3 microequiv./min) and mean arterial pressure (+ 20 mmHg (1 mmHg = 133.322 Pa)). Central venous pressure decreased 6.5 mmHg, as did hematocrit (from 45.7 to 39.8%) and plasma protein concentration (from 5.88 to 5.15 g%). Pericardiocentesis had no significant effect on renal blood flow (RBF), nor plasma flow. Redistribution of glomerular filtrate was suggested by the observation that superficial nephron glomerular filtration rate increased (from 91 to 108 nL/min) while glomerular filtration rate remained unaltered. Determination of intrarenal distribution of RBF revealed that cortical blood flow also distributed superficially. A significant increase in the fraction of RBF perfusing zone 1 (outer cortex) and a decrease in fractional perfusion of zones 2, 3 and 4 (juxtamedullary cortex) were observed in each experiment following pericardiocentesis. RBF distribution examined in a series of six animals prior to and during the development of pericardial tamponade showed the opposite effect. These results indicate that pericardiocentesis causes redistribution of both glomerular filtrate and RBF to superficial nephrons. The development of pericardial tamponade was associated with increased fractional juxtamedullary blood flow. These changes may have been the result of altered blood pressure, hematocrit, plasma protein concentration, or altered renal resistance.     

Rheological properties of the blood influencing selectin-mediated adhesion of flowing leukocytes

We studied how the rheological properties of blood influenced capture and rolling adhesion of leukocytes as well as their margination in the bloodstream. When citrated, fluorescently labeled blood was perfused through glass capillaries coated with P-selectin, leukocytes formed numerous rolling attachments. The number of attached leukocytes increased as the hematocrit was increased between 10% and 30% and was essentially constant from 30% to 50%. In EDTA-treated blood, adhesion was absent, and the flux of marginated cells varied little with increasing hematocrit. However, the velocity of marginated leukocytes increased monotonically, whereas the volumetric flow rate was constant, implying that the flow velocity profile became blunted and wall shear rate increased. Thus increasing hematocrit promoted attachment for a given total flow rate, without increasing margination, even though wall shear rate and blood viscosity increased. Blood was diluted to 20% hematocrit with plasma, 40-kDa dextran (to reduce red blood cell aggregation), or 500-kDa dextran (to enhance aggregation). Increasing aggregation correlated with increasing leukocyte adhesion and with more slow-flowing leukocytes near the wall. Thus flowing erythrocytes promote leukocyte adhesion, either by causing margination of leukocytes or by initiating and stabilizing attachments that follow.