Hemodynamic Resistance Research Articles

Computer and Physical Modeling of Blood Circulation Pump Support for a New Field of Application in Palliative Surgery

One of the most popular palliative procedures performed to increase pulmonary blood flow in children with congenital heart defects is a shunt operation (Blalock-Taussig graft or Glenn procedure), which creates the new blood channel to the pulmonary artery. The main problem with this kind of surgery is poor shunt effectiveness and the lack of possibility to regulate the flow. The aim of this work is to use advanced computer simulation methods to study the effectiveness of a new idea to introduce a small axial blood pump into a Blalock-Taussig (B-T) or Glenn shunt in order to control the blood flow and prevent any increase in the graft stenosis. Physical and computer 3-D simulation based on a finite element mesh (FEM) model was applied. Studies for optimization of the shunt and hybrid shunt with pump were performed for different stages of the disease. The graft with the axial pump creates good conditions for the vascular system and pulmonary artery blood flow as well as regulating blood pressure under variable conditions caused by palliative procedures. Its use permits the afterload of the left heart ventricle to be decreased. A palliative procedure is only a temporary solution. When a child grows, while the graft size is fixed, the blood flow through this graft may be not sufficient under changing hemodynamic conditions. The use of an axial pump for regulating the blood flow volume, during palliative procedures, allows to obtain the optimal flow conditions in pulmonary artery and safely wait on the final cardiac surgery correction later. However, the use of a pump mounted inside the graft increased hemodynamic resistance, which caused the flow to decrease up to 70% in the graft when the axial pump was not working.

Pseudo-organ boundary conditions applied to a computational fluid dynamics model of the human aorta

In three-dimensional numerical studies of the aorta, it is difficult to apply proper boundary conditions at the end of each major aortic branch because of interactions between blood and organs. Organs and body parts were assumed to be likened to cylindrically shaped porous media, so-called pseudo-organs, and treated in the computational domain as forms of hemodynamic resistance. Permeability functions were determined from two-dimensional axisymmetric computations of each aortic branch and these functions were then used in an unsteady three-dimensional simulation of the complete aorta. Substantially accurate cardiac output (5.91 L/min) and blood distributions to the major branches were predicted.

DIDECMO: a new polymethylpentene oxygenator for pediatric extracorporeal membrane oxygenation.

We reviewed the performance of a new polymethylpentene oxygenator (DIDECMO, Dideco, Mirandola, Italy) in terms of clinical safety and efficiency in priming, oxygenation, and oxygenator resistance in neonatal and pediatric extracorporeal membrane oxygenation (ECMO) patients. Between March 2005 and January 2006, 14 patients required ECMO in the San Vincenzo Hospital. Of these, 8 (median age, 9 days; range, 3 days to 15 months) received normothermic ECMO for postcardiotomy heart failure after surgery for congenital heart disease. The DIDECMO oxygenator was used in all patients (median weight, 2.4 kg; range, 2 to 7 kg). According to our previous experience, all patients received the same anticoagulation management. DIDECMO is a new phosphorylcholine-coated, polymethylpentene hollow-fiber oxygenator recommended for a maximum blood flow of 2300 ml/min with a membrane surface area of 0.67 m2 and validated to be used up to 5 days. Static priming was 100 ml and mean support time 05 hours (range, 36 to 198 hours). No oxygenators were changed during support. Median pressure drop during overall assistance was 24 mm Hg. Carbon dioxide elimination was obtained with a 1:1 blood flow/air flow ratio. Neither oxygenator-related major nor minor adverse events occurred during support. In our initial experience, the new polymethylpentene DIDECMO oxygenator provided adequate gas exchange and offered technical advantages in terms of low priming volume and acceptable hemodynamic resistance despite pulsatile flow regimen. Also, we used this device for more than 8 days without any technical problems.

Three-Dimensional Rotational Angiographic Detection of In-Stent Stenosis in Wide-Necked Aneurysms Treated with a Self-Expanding Intracranial Stent

To determine the effect of Neuroform stent (Boston Scientific/Target, Fremont, CA) deployment on parent vessel lumen and detect in-stent changes in patients harboring wide-necked intracranial aneurysms treated with the stent-coil technique. Parent vessel dimensions were quantified before and after the procedure and at intermediate follow-up examinations by use of high-resolution three-dimensional rotational angiography. By use of shaded surface segmentation of the acquired volume, measurements of the parent vessel proximal to the stent (Point A), at three points within the stented vascular segment (Points B, C, and D), and distal to the stent (Point E) at each study time were compared by use of paired t tests. Correlation between degree of in-stent stenosis and reported ischemic events was estimated by use of a linear regression model. Stent and coil deployment had no immediate effect on parent vessel dimensions. At angiographic follow-up, there was no significant change in vessel size proximal to the stent. Within the stent and distal to it, however, there was a statistically significant 0.31- to 0.41-mm reduction in average diameter (P < 0.001, P < 0.011, P < 0.003, and P < 0.014 for Points B, C, D, and E, respectively). The highest degree of stenosis occurred at Point B, with an average decrease in cross sectional surface area of 2.4 mm (P < 0.001), corresponding to a 19% stenosis and 52% estimated increase in focal hemodynamic resistance by Poiseuille's law. No clinical correlation was noted with the degree of in-stent stenosis. Intracranial stenting using a soft self-expanding stent without angioplasty induced a statistically, but not clinically, significant decrease in cross sectional area. Further research and longer-term follow-up are needed to elucidate the mechanism and clinical importance of this response.

Clinical Evaluation of the Sorin Synthesis™ Oxygenator With Integrated Arterial Filter

The use of arterial line filters has long been a standard of practice in the field of cardiopulmonary bypass. Sorin Biomedica has designed an adult hollow-fiber oxygenator that not only incorporates their Mimesys® biomimicry coating technology but also has a 40-micron arterial filter as an integrated component of this unique membrane oxygenator. We did a prospective, randomized clinical trial of 54 Synthesis® coated oxygenators and compared them with 54 uncoated Monolyth Pro® oxygenators, the latter of which incorporated an external arterial line filter with a standard bypass loop There were few statistically significant differences found between the Synthesis® group and the Monolyth group with regard to pressure differentials, hemodynamic resistance, and platelet drop. The Synthesis® oxygenator did require less priming volume, but the amount was not significant. Platelet counts with the Phosphorylcholine coated Synthesis oxygenators, using crystalloid perfusates, was similar to our previously published data on platelet protection and Albumin perfusates. We conclude that the Sorin Synthesis® oxygenator appears to have better flow characteristics than the Monolyth oxygenator, with the potential for lower priming volumes. The most clinically significant benefit comes from the elimination of the arterial filter bypass loop and the avoidance of inverting the arterial filter during priming.

Performance of polymethyl pentene oxygenators for neonatal extracorporeal membrane oxygenation: a comparison with silicone membrane oxygenators

To review the performance of polymethyl pentene versus silicone oxygenators in terms of efficiency in priming and oxygenation, oxygenator resistance, requirements for coagulation proteins and consumption of blood products, for neonatal extracorporeal membrane oxygenation (ECMO) patients. Forty consecutive neonates were selected retrospectively pre- and post-introduction of the new polymethyl pentene (PMP) oxygenators. They formed two equal groups. After calculation of the sample size, data were collected from ELSO registry forms and patient records. Results were analysed using parametric and non-parametric tests. Neonatal PMP (N-PMP) oxygenators were smaller, faster and easier to prime. They were less efficient than silicone oxygenators, especially in carbon dioxide elimination, and, therefore, required higher sweeps. The preservation of coagulation proteins was significantly better, but there was no reduction in the consumption of blood products, despite having less than half the surface area and significantly lower blood path resistance. Small PMP oxygenators (Medos Hilite 800 LT) provide adequate gas exchange and offer technical advantages in terms of more efficient priming, reduced haemodynamic resistance and better control and preservation of coagulation proteins than silicone oxygenators.

Haemodynamic resistance model of monochorionic twin pregnancies complicated by acardiac twinning

An acardiac twin is a severely malformed monochorionic twin fetus that lacks most organs, particularly a heart. It grows during pregnancy, because it is perfused by its developmentally normal co-twin (called the pump twin) via a set of placental arterioarterial and venovenous anastomoses. The pump twin dies intrauterine or neonatally in about 50% of the cases due to congestive heart failure, polyhydramnios and prematurity. Because the pathophysiology of this pregnancy is currently incompletely understood, we modified our previous haemodynamic model of monochorionic twins connected by placental vascular anastomoses to include the analysis of acardiac twin pregnancies. We incorporated the fetoplacental circulation as a resistance circuit and used the fetal umbilical flow that perfuses the body to define fetal growth, rather than the placental flow as done previously. Using this modified model, we predicted that the pump twin has excess blood volume and increased mean arterial blood pressure compared to those in the acardiac twin. Placental perfusion of the acardiac twin is significantly reduced compared to normal, as a consequence of an increased venous pressure, possibly implying reduced acardiac placental growth. In conclusion, the haemodynamic analysis may contribute to an increased knowledge of the pathophysiologic consequences of an acardiac body mass for the pump twin.

Contribution of fluid shear response in leukocytes to hemodynamic resistance in the spontaneously hypertensive rat.

The mechanisms for elevation of peripheral vascular resistance in spontaneously hypertensive rats (SHR), a glucocorticoid-dependent form of hypertension, are unresolved. An increase in hemodynamic resistance caused by circulating blood may be a factor. Physiological fluid shear stress induces a variety of responses in circulating leukocytes, including pseudopod retraction. Due to high rigidity, leukocytes with pseudopods have greater difficulty to pass through capillaries. Because SHR have more circulating leukocytes with pseudopods, we hypothesize that inhibition of the leukocyte shear response by glucocorticoids in SHR impairs normal leukocyte passage through capillaries and causes enhanced resistance in capillary channels. Fluid shear leads to retraction of pseudopods in normal leukocytes, whereas shear induces pseudopod projection in SHR and dexamethasone-treated Wistar rats. The high incidence of circulating leukocytes with pseudopods results in slower cell passage through capillaries under normal blood flow and during reduced flow enhanced capillary plugging both in vivo and in vitro. SHR blood requires higher pressure (90.0+/-8.2 mm Hg) than Wistar Kyoto rat (WKY, 69.6+/-6.5 mm Hg; P<0.0001) or adrenalectomized SHR (73.5+/-2.1 mm Hg; P=0.0009) at the same flow rate in the resting hemodynamically isolated skeletal muscle microcirculation. Intravenous injection of blood from SHR, but not WKY, causes blood pressure increase in normal rats, which depends on pseudopod formation. We conclude that in addition to enhanced vascular tone, pseudopod formation with lack of normal fluid shear response may serve as mechanisms for an elevated hemodynamic resistance in SHR.

Evaluation of Mimesys® Phosphorylcholine (PC)-Coated Oxygenators during Cardiopulmonary Bypass in Adults

A new generation of coating extracorporeal circuitry with biocompatible polymers has entered the North American perfusion market. This new biomimetic coating process uses synthetic phosphorylcholine (PC) containing polymers to bond covalently to the surface of the Sorin Monolyth® oxygenator, under the brand name of Mimesys®. In part one of a three-part investigation, 160 Mimesys®-coated oxygenators were randomly evaluated against 36 uncoated oxygenators for blood flow, hemodynamic resistance, and pressure differentials. In part two, retrospective analysis of platelet data collected in this study was compared with platelet data collected from a previous investigation using uncoated Monolyth oxygenators with albumin and crystalloid perfusates. Part three examined the risk-adjusted oxygenators, compared with 71 case-matched patients treated with uncoated oxygenators. There was no difference found in the Mimesys-coated group, when compared to the control group, with regard to pressure differentials or hemodynamic resistance. However, we conclude that platelet protection with PC-coated Monolyth’s using crystalloid perfusates, was similar to platelet protection with albumin perfusates, and significantly better than uncoated Monolyths® using crystalloid perfusates.

A new method for assessing arteriolar diameter and hemodynamic resistance using image analysis of vessel lumen.

To characterize the nonuniform diameter response in a blood vessel after a given stimulus (e.g., arteriolar conducted response), frequent serial diameter measurements along the vessel length are required. We used an advanced image analysis algorithm (the "discrete dynamic contour") to develop a quick, reliable method for serial luminal diameter measurements along the arteriole visualized by intravital video microscopy. With the use of digitized images of the arteriole and computer graphics, the method required an operator to mark the image of the two inner edges of the arteriole at several places along the arteriolar length. The algorithm then "filled in" these marks to generate two continuous contours that "hugged" these edges. A computer routine used these contours to determine luminal diameters every 20 microm. Based on these diameters and on Poiseuille's law, the routine also estimated the hemodynamic resistance of the blood vessel. To demonstrate the usefulness of the method, we examined the character of spatial decay of KCl-induced conducted constriction along approximately 500-microm-long arteriolar segments and the KCl-induced increase in hemodynamic resistance computed for these segments. The decay was only modestly fitted by a simple exponential, and the computed increase in resistance (i.e., 5- to 70-fold) was only modestly predicted by resistance increase based on our mathematical model involving measurements at two arteriolar sites (Tyml K, Wang X, Lidington D, and Oullette Y. Am J Physiol Heart Circ Physiol 281: H1397-H1406, 2001). We conclude that our method provides quick, reliable serial diameter measurements. Because the change in hemodynamic resistance could serve as a sensitive index of conducted response, use of this index in studies of conducted response may lead to new mechanistic insights on the response.

Microvascular structure and function in salt-sensitive hypertension.

In many individuals with essential hypertension, dietary salt can further increase blood pressure by augmentation of an already elevated total peripheral resistance. There is little information on the microvascular changes that contribute to salt-sensitive hypertension in humans, but studies in the Dahl salt-sensitive rat have provided some knowledge of the microcirculation in this form of hypertension. These studies, most of which have used intravital microscopy or isolated vessel technology, are the focus of this review. The salt-induced exacerbation of hypertension in Dahl rats is due to a uniform increase in hemodynamic resistance throughout most of the peripheral vasculature. In the spinotrapezius muscle, this resistance increase is largely due to the intense constriction of proximal arterioles. The mechanisms responsible for this increased arteriolar tone include increased responsiveness to oxygen and a loss of tonic nitric oxide (NO) availability caused by reduced endothelial NO production and/or accelerated NO degradation by reactive oxygen species. Within the last decade, it has become increasingly clear that high salt intake can also lead to changes in microvascular structure and function in the absence of increased arterial pressure. This effect must also be considered when evaluating microvascular changes and their functional consequences in salt-sensitive hypertension.

Arterial stiffness and gradient of blood pressure at essential hypertension

The two major causes of increased large artery stiffness are aging and high blood pressure. This study was designed to assess the modifications in large artery elastic properties and their hemodynamic resistance at essential hypertension (EH). The pulse wave velocity (PWV) was evaluated in the following distance: carotid-femoral artery, femoral-posterior tibial artery and carotid-radial artery by piezoelectric detectors. The gradient of arterial pressure (AP) was analyzed in the distance: brachial-finger artery and brachial-posterior tibial artery applying auscultatory method (using acoustic system), and, simultaneously, the gradient of systolic AP was evaluated according to volume oscillations. Data were analyzed in supine position, when intravascular pressure was modified by rising and lowering the extremity referring to the heart level, and when subjects was passively tilted up to 70° with and without unilateral thigh arterial occlusion for 5 min. Group of 78 patients with EH (38-57 yrs aged men) and 31 age and gender matched controls were studied. Antihypertensive treatment, if any, was interrupted 8 days before the examination. In EH pts mean AP gradient in the distance of brachial-finger artery was increased (14.1±1.4 vs. 8.7±1.7 mmHg; P<0.02), whereas systolic and pulse pressure on tibial artery comparing to brachial artery was increased (Franc's phenomenon) and this increase was more expressed in EH pts (35.2±5.4 vs. 18.5±2.3 mmHg; P<0.02) and related (r=0.63; P<0.01) to systemic AP level. Upper extremity lowering and subjects tilting was related with less than expected (calculated hydrostatic pressure) increase of AP in distal parts. This difference disappeared on background of unilateral reactive hyperemia. At upper extremity elevation, decrease of finger AP corresponded to expected hydrostatic pressure decrease in both groups. In all analyzed distances PWV values were increased in EH pts comparing to controls (P<0.001) and were related to systemic arterial (brachial) pressure level (r=0.51-0.59; P<0.01). Modifications in regional AP caused by hydrostatic effect was related with corresponding PWV changes (r=0.8 in EH pts and r=0.72 in controls). This study suggests that alongside increased wall stiffness the hemodynamic resistance of large arteries is increased at EH and modifications in smooth muscle tone maintain important role in systemic and regional hemodynamic reactions.

Changes in flow velocity, resistance indices, and cerebral perfusion pressure in the maternal middle cerebral artery distribution during normal pregnancy

There are few longitudinal data currently available detailing the normal changes in maternal cerebral hemodynamics during human pregnancy. This lack of information limits the study of pregnancy-associated cerebrovascular adjustments and, in particular, preeclampsia, where the brain appears to be especially susceptible to ischemic and encephalopathic injury. Our objective was to define the hemodynamic changes, specifically velocity, resistance indices, and cerebral perfusion pressure, in the middle cerebral artery (MCA) distribution of the brain during normal pregnancy. Transcranial Doppler ultrasound was used to determine the systolic, diastolic and mean blood velocities in the middle cerebral arteries in non-laboring women studied longitudinally during normal gestation. The resistance index (RI), pulsatility index (PI), and cerebral perfusion pressure (CPP) were calculated using the velocity and blood pressure data. Data were analyzed using a longitudinal statistical model incorporating random patient effects and a homoscedastic (compound symmetric) variance-covariance structure over time (gestational age). The predicted mean value (Least Squares Mean), and the 5th and 95th percentiles, were defined for normal pregnancy. MCA systolic velocity decreased (24%) as did the mean velocity (17%). The diastolic velocity did not change significantly. The MCA RI decreased by 19% and the PI decreased by 25%. The MCA CPP increased by 52% between 12 and 40 weeks of gestation. The normative ranges for MCA velocity, RI, and CPP have been defined in normal human pregnancy using longitudinally collected data. By having a defined normal range, identification of abnormalities in cerebral hemodynamics during pregnancy is now possible, and this may help researchers and clinicians to elucidate etiologies and treatments for pregnancy-related pathophysiologic states such as preeclampsia

Measurement of primary haemostasis using a pressure clamp technique

With the PFA-100 ™ a sensitive and specific screening test for primary haemostasis has recently become available. An important part of the device is a capillary, providing a defined haemodynamic resistance for the perfusion of the aperture. A modified method to measure platelet function (VCP2) is presented in which the capillary essentially is replaced with an 'electronic capillary' by clamping the pressure/flow relationship. Results and conclusion: Closure time (CT) and blood volume (BV) as determined by PFA-100 ™ and VCP2 correlated well within ( r = 0.922 - 0.952) and between the two methods ( r = 0.86). The test variability (CV) of CT could be significantly reduced in the VCP2 method (collagen/epi 3.9 vs. 5.9%, p <0.05; collagen/ADP 3.3 vs. 6.9%, p <0.001), thus considerably increasing test reliability and reducing test variance. In preliminary clinical studies the VCP2 system showed comparable sensitivity for vWD and slightly less sensitivity regarding ASA ingestion. The test spectrum of VCP2 could be extended to more thrombocytopenic samples ( h 20 000/ w l) even in combination with low haematocrit levels (20%), thus perhaps permitting the determination of the bleeding risk in bone marrow hypoplasia. Additionally, the sensitivity and applicability can easily be adapted to the desired need only by software modifications.

Nitrate resistance in platelets from patients with stable angina pectoris.

Hemodynamic resistance to nitrates has been previously documented in congestive heart failure. In patients with stable angina pectoris (SAP), we have observed a similar phenomenon: decreased platelet response to disaggregating effects of nitroglycerin (NTG) and sodium nitroprusside (SNP). In blood samples from normal subjects (n=32) and patients with SAP (n=56), we studied effects of NO donors (NTG and SNP) on ADP-induced platelet aggregation and on intraplatelet cGMP. NTG and SNP inhibited platelet aggregation in patients to lesser extents than in normal subjects (P<0.01). The cGMP-elevating efficacy of NTG and SNP was diminished in platelets from patients in comparison with those from normals (P<0.001). Inhibition of the anti-aggregatory effects of NTG and SNP by ODQ, a selective inhibitor of NO-stimulated guanylate cyclase, was significantly less pronounced in patients than in normal subjects. Content of O2- was higher in blood samples from patients than in those from normal subjects (P<0. 01). In blood samples from patients with SAP, but not in normal subjects, the O2- scavenger superoxide dismutase (combined with catalase) suppressed platelet aggregation (P<0.01) and increased the extent of anti-aggregatory effect of SNP (P<0.01). In patients with SAP, platelets are less responsive to the anti-aggregating and cGMP-stimulating effects of NO donors; this may reflect both reduction in guanylate cyclase sensitivity to NO and inactivation of the released NO by O2-. The implied impairment of anti-platelet efficacy of endogenous NO (in the form of EDRF) may contribute to platelet hyperaggregability associated with angina pectoris.

Effects of Skeletal Muscle Sarcomere Length onin VivoCapillary Distensibility

The structural integrity of the capillary wall is such that capillary luminal distensibility is largely determined by support provided by the tissue in which it is located. Given that O2 flux density is greatest across the skeletal muscle capillary endothelium, any changes in capillary diameter (dc) would be expected to affect O2 diffusing capacity as well as hemodynamic resistance. We used intravital microscopy techniques to study the maximally vasodilated rat (n = 5) spinotrapezius muscle microcirculation in vivo within the physiological sarcomere length range, at high and low mean arterial pressures (MAP) systematically altered by blood withdrawal and infusion. We tested the hypothesis that in vivo capillary diameter alterations in response to changes of MAP would be reduced at extended sarcomere lengths. At 2.4-microm sarcomere length, mean dc (dc) within the spinotrapezius increased from 5.6 +/- 0.1 to 5.9 +/- 0.1 microm (P < 0.01) as MAP increased from 33 to 94 mm Hg. However, there was absolutely no change (i.e., 5.2 +/- 0.1 vs 5.2 +/- 0.1 microm) in dc in response to changes in MAP at 3.2-microm sarcomere length. Furthermore, at sarcomere lengths <2.8 microm there was a significant increase (P < 0.01) in dc (n = 40) as MAP increased, whereas dc (n = 49) remained unchanged with alterations of MAP when sarcomere length was >/=2.8 microm (P > 0.05). These data suggest that pressure-induced alterations in capillary luminal diameter and thus "in vivo capillary distensibility" are dependent upon the presiding sarcomere length. Furthermore, we conclude that the MAP-induced increases in capillary luminal diameter at the shorter sarcomere lengths are modest ( approximately 5%) and unlikely to affect O2 diffusing capacity and vascular resistance appreciably.

The role of vague nerve in the hemodynamic changes induced by acute biliary tract pressure increase.

In order to explore the mechanism of hemodynamic changes caused by high biliary tract pressure, we established an animal model of high biliary tract pressure, in which the disturbance of hemodynamics developed. The cervical or abdominal vague nerve was then blocked. It was observed that when the biliary tract pressure was increased to 16 kPa and kept for 1 h, the arterial blood pressure and cardiac output decreased immediately and parallelly (P < 0.05). When the cervical or abdominal vague nerve were blocked or the pressure of the biliary tract was decreased to zero, both indices returned to normal immediately (P > 0.05). The change of cardiac output lags a little behind that of arterial blood pressure. It suggests that the signal of biliary tract pressure increase can be sent to the cardiovascular center through vague nerve, and the balance between sympathic and parasympathic nerve was broken, which led to the weakening of cardiac contraction and decrease of cardiac output. Due to the peripheral effects of vague nerve, hemodynamic resistance of vessels decreased, which brought about redistribution of peripheral blood flow. Both were the causes of hemodynamic disturbances. After the blood pressure decreased markedly, it showed a jump to normal state when cervical vague nerve was blocked. And the amplitude of diastolic blood pressure restored more than that of systolic blood pressure. This suggests that the cardiac output and peripheral blood resistance are important factors that cause the decrease of blood pressure.

Mechanisms for increased blood flow resistance due to leukocytes

Despite the small number of leukocytes relative to erythrocytes in the circulation, leukocytes contribute significantly to organ blood flow resistance. The present study was designed to investigate whether interactions between leukocytes and erythrocytes affect the pressure-flow relationship in a hemodynamically isolated rat gracilis muscle. At constant arterial flow rate, arterial pressure was increased significantly when relatively few physiological counts of leukocytes were added to a suspension containing erythrocytes at physiological hematocrits. However, the arterial pressure after perfusion of similar numbers of isolated leukocytes without erythrocytes was only slightly increased. An increase in resistance was also observed when leukocytes were replaced with 6-micron microspheres. We propose a new mechanism for increasing the hemodynamic resistance that involves hydrodynamic interactions between leukocytes and erythrocytes. In the presence of larger and less deformable leukocytes, erythrocytes move through capillaries more slowly than without leukocytes. Therefore erythrocytes are displaced from their axial positions. Slowing and radial displacement of erythrocytes serve to increase the relative apparent viscosity attributable to erythrocytes, thereby causing a significant elevation of organ blood flow resistance.

Biomechanics of skeletal muscle capillaries: hemodynamic resistance, endothelial distensibility, and pseudopod formation.

The objective of this study was to investigate the structure of capillaries in rat skeletal muscle and their mechanical properties over a wide range of transmural pressures. Capillaries were fixed at controlled pressures and studied with intravital and electron microscopy. Capillary lumen dimensions depend on the local transmural pressure, with irregular and partially collapsed cross-sections at low transmural pressures and circular cross-sections at elevated pressures. The average circumferential wall stress is a nonlinear function of the circumferential stretch. Elevation of the transcapillary pressure serves to increase the endothelial surface area exposed to the lumen and to the basement membrane while the average endothelial thickness and cell volume decrease. The number of vesicles in the endothelium and their average size decrease with the stretching of the endothelial cell. The balance of membrane area measurements on the vesicles and on the cell surface show that the total membrane surface is conserved at all pressures, and the vesicles become unfolded during stretching of the endothelial cells. This suggests that the vesicle membrane serves as a reservoir for the increase of endothelial surface membrane area during capillary distension. Under normal or elevated capillary pressure, virtually no evidence for pseudopod formation by the endothelial cells was detected. If the capillary transmural pressure was reduced to zero in the presence of autologous plasma for periods of about 10 min, limited evidence for pseudopods in less than 10% of the capillary sections was seen. If the muscle capillaries were perfused with plasmalyte and fixed at low pressures, all capillaries exhibited pseudopod formation. Addition of plasma proteins prevented most pseudopod formations. Endothelial pseudopods are depleted of vesicles and form sheet-like projections. Once pseudopods are formed at low pressure, they cannot readily be unfolded by elevation of the capillary transmural pressure. Pseudopods appear to consist of a crosslinked actin matrix and may have a strong effect on the resistance to blood flow in capillaries. These results may be relevant with respect to capillary blood flow at low pressures.

Exercise training-induced increase in coronary transport capacity

The objective of this study was to measure effects of exercise training on coronary flow heterogeneity, microvascular transport, and hemodynamics. Five miniature swine were trained on a treadmill (ET) for 16 wk; five control pigs (C) were confined to cages for the same period. At the end of that period we used the multiple indicator dilution method to measure permeability-surface area product (PS) to EDTA over a range of flow (F) in an anesthetized, open-chest preparation. We found that the heterogeneity of flow as measured by microspheres decreased with increasing F, but that ET had no clear effect on heterogeneity. We evaluated PS from the indicator concentration curves, taking into account flow heterogeneity and variations in capillary recruitment throughout the bed. In both C and ET pigs we observed an increase in PS with F until a maximum value of PS was reached at full recruitment. This relationship between PS and F was unaltered by ET. However, hemodynamic resistance was significantly reduced by ET, and F was higher at a given perfusion pressure after training. Since PS increases with F, ET pigs had higher PS values at typical coronary artery pressures.