Biomedical subjects

S P Sutera

Publications and source records attributed to S P Sutera.

At least 19 recordsLinked to original sources

PubMed1998

Platelet adhesion and aggregation in pulsatile shear flow: effects of red blood cells.

An in vitro test system was developed to examine the effects of red blood cells (RBC) on shear-induced platelet adhesion (SIPAD) and platelet aggregation (SIPAG). Suspensions of human platelets labeled with Mepacrine and suspended in citrated plasma were exposed to single, continuous or repetitive (120-300x) one second shear stress pulses of varying amplitude (15-100 dyn/cm2) in a cone-plate viscometer in the presence or absence of fresh, untreated (intact) RBC or glutaraldehyde (GLA)-fixed, rigid, adenosine diphosphate (ADP)-depleted (GLA)-RBC. SIPAG was expressed as percent loss of single platelets. SIPAD was assessed by measuring the amount of Mepacrine-related fluorescent material remaining on glass disks in the plate of the viscometer after washing with EDTA-saline to remove platelet aggregates. Intact RBC were twice as effective as GLA-RBC in potentiating SIPAG at all shear stress levels. Potentiation of SIPAD by intact RBC was markedly less than that observed with GLA-RBC at stresses below 50 dyn/cm2. These findings are consistent with the concept that while both physical and chemical (ADP) mechanisms are substantially involved in potentiation by RBC of SIPAG, RBC support SIPAD largely by enhancement of platelet transport from the bulk flow to the bounding surfaces. The findings also indicate that it is feasible to assess SIPAD and SIPAG in the same flow system simultaneously. A less complicated version of the method described here should prove useful in the evaluation of patients with platelet functional disorders, and in the evaluation and monitoring of antiplatelet agents.

Blood Platelets↗

PubMed1996

Effect of chronic oral pentoxifylline administration on murine erythrocyte deformability.

BACKGROUND: Pentoxifylline has been reported to increase radiation sensitivity in vivo. We sought to evaluate whether this effect is mediated by changes in murine erythrocyte flexibility. METHODS: Pentoxifylline was administered via liquid or solid diet to young adult male CF-1 mice for 1-6 weeks. After 1, 3, and 6 weeks of drug administration, plasma levels of pentoxifylline and major derivatives were measured and erythrocyte deformability was assessed by rheoscopy, a technique which permits direct measurement of individual cellular dimensions. RESULTS: Contrary to prior reports, we found no discernible effect of the drug on erythrocyte deformability. CONCLUSIONS: The beneficial effect of pentoxifylline administration on radiation sensitivity in tumor-bearing mice is mediated by other mechanisms.

Administration, Oral↗

PubMed1996

Pierce-Donachy pediatric VAD: progress in development.

BACKGROUND: Despite the successful use of ventricular assist devices in adults over the past 15 years, relatively little has been done to develop similar devices for pediatric patients. Consequently, no such device is currently available. A review of clinical data suggests that the majority of patients in need of a pediatric ventricular assist device, either for postcardiotomy cardiogenic shock or as a bridge to cardiac transplantation, are neonates weighing 3 to 5 kg. Attempts to "scale down" an adult blood pump to make an appropriate device for these patients have been difficult due to the lack of sufficiently small, commercially available valves and the tendency for thrombus to develop in these small pumps. METHODS: We report on progress in the development of the Pierce-Donachy pediatric ventricular assist device, which incorporates 10-mm-diameter bileaflet valve prototypes. Particle image velocimetry is used to quantify the velocity field inside the pump. RESULTS AND CONCLUSIONS: Particle image velocimetry velocity maps demonstrate the complexity of the flow patterns in these pumps and suggest that improved flow patterns may result from the use of valves with improved hemodynamic performance. Animal tests to determine whether improved flow patterns and better "washing" of the pump's blood-contacting surfaces will reduce thrombus formation are underway.

Animals↗

PubMed1996

Evidence for acute renal cortical vasoconstriction after uninephrectomy.

The rate of progression of chronic renal failure (CRF) is similar for many diseases, suggesting a common, perhaps intrinsic, renal signal for its progression. The remnant nephron hypothesis of Bricker suggests that CRF may be the result of persistent compensatory renal growth (CRG). Normally, CRG after unilateral nephrectomy (uniNx) ceases within 1 week. Knowledge of the signals that initiate CRG may therefore shed light on the signals responsible for ongoing CRF. The signals responsible for the initiation of compensatory renal growth after uniNx are unknown. Hemodynamic changes in the remaining renal artery have been observed, but there are as yet no data for the main renal compartment which undergoes hypertrophy, the superficial renal cortex. The noninvasive technique of laser-Doppler flowmetry allows the continuous and independent monitoring of blood velocity and blood volume. The product of the two signals is proportional to tissue blood flow per unit volume of the tissue observed. Under controlled conditions in adult male Sprague-Dawley rats, renal cortical blood velocity increased by 22% within 5 min after uniNx and remained elevated at this level for 60 min. Renal cortical blood volume decreased throughout the experiment. Their product, renal cortical blood flow, increased briefly by 14% 5 min after uniNx but decreased over the time of observation in parallel with renal cortical blood volume. The simultaneous increase in blood velocity and decrease in blood volume in the superficial renal cortex acutely after uniNx suggest that vasoconstriction is an early event in compensatory renal growth.

Acute Disease↗

PubMed1992

Concurrent increases in regional hematocrit and blood flow in diabetic rats: prevention by sorbinil.

These studies were undertaken to investigate the relationship between regional hemodynamic and hemorheological changes in the microvasculature of diabetic rats. Diabetes was induced in male Sprague-Dawley rats by injection of streptozotocin (55 mg/kg body wt). Control rats were injected with vehicle (sodium citrate buffer). A subgroup of diabetic rats was treated with an aldose reductase inhibitor (sorbinil) added to the diet in an amount to provide a daily dose of approximately 0.2 mmol.kg-1.day-1. Three weeks later all animals were anesthetized with thiobutabarbital sodium (Inactin, 100 mg/kg injected intraperitoneally) for assessment of blood flow (by injection of 15 microns microspheres) and regional hematocrit (determined by isotope-dilution techniques using 51Cr-labeled red blood cells and 125I-labeled bovine serum albumin) in selected tissues. The hematocrit in arterial blood samples was identical (approximately 46%) in controls and in diabetics. Regional hematocrits were much lower than arterial hematocrits in control rats and ranged from approximately 20% in ocular tissues, sciatic nerve, diaphragm, and skin to approximately 30% in brain, skeletal muscle, heart, and fat. Hematocrits of diabetic rats were markedly increased in ocular tissues, sciatic nerve, and skin but not in brain, heart, or skeletal muscle. These increases in regional hematocrit were associated with increases in blood flow and were largely prevented by sorbinil. Diabetes induced significant decreases in the mean transit times for whole blood and erythrocytes in all tissues examined except brain, retina, and skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗

PubMed1991

Discordant effects of nisoldipine on coronary vascular resistance and permeability changes during reflow after ischemia in isolated rabbit hearts.

Effects of a low dose (5 nM) of nisoldipine on vascular and ventricular function were assessed in isolated rabbit hearts during 2 h of reperfusion after 40 min of global, zero-flow ischemia. External detection of bolus injections of 125I-BSA and pressure data generated during the experiment provided repeated estimates of albumin permeation and vascular hemodynamics (resistance, vascular volume, and fractional rate of intravascular washout of 125I-BSA (k01]. In control hearts perfused continuously for 3.5 h, vascular resistance, vascular volume, LVEDP, and k01 remained constant, while maximum +dP/dt and -dP/dt increased 25% above baseline values, and estimates of albumin permeation increased 1.7 x baseline. Addition of 5 nM nisoldipine to the perfusate after the baseline period produced sustained decreases in vascular resistance (16% vs mean baseline value) without significantly affecting any other parameter. Postischemic perfusion of hearts increased vascular resistance and vascular volume approximately 50% above baseline, decreased k01 by 25% (intravascular washout of 125I-BSA was prolonged), and increased albumin permeation approximately 5 x baseline. While LVEDP remained elevated 3 x baseline, maximum +dP/dt and -dP/dt recovered 100% of baseline values (75-80% of untreated control values at comparable time points). Addition of 5 nM nisoldipine to the perfusate prior to ischemia prevented the increased vascular resistance during reflow, prevented the decrease in k01 and the increase in vascular volume, but did not affect the increased albumin permeation and, in general, did not affect the rate of recovery of left ventricle function. These results indicate that a low dose of nisoldipine preserves postischemic coronary vascular hemodynamics, but has little or no effect on the increased vascular leakage of albumin.

Animals↗

PubMed1991

Reduction of the surface-volume ratio: a physical mechanism contributing to the loss of red cell deformability in malaria.

Plasmodia and other intraerythrocytic parasites reduce the deformability of the red cells they infect. One mechanism potentially responsible for this reduction in deformability is the decrease in the surface:volume (S/V) ratio of the red cell which occurs with parasite growth. To examine this hypothesis, normal red cells were allowed to phagocytize polylysine-coated latex spheres 1.0 to 2.9 microns in diameter. Deformability decreased progressively with spheres of increasing size, consistent with the decreasing S/V ratios of those cells (from an initial length:width [L/W] ratio of 2.398 +/- 0.549 for normal red cells to 1.559 +/- 0.249 for red cells containing 2.92 microns latex spheres at 40 dynes per cm2, p less than 0.001). Nevertheless, red cells containing latex spheres 2.0-2.9 microns in diameter remained deformable and continued to tank tread, in contrast to red cells containing Plasmodium falciparum parasites of that size, which are not deformable and do not tank tread. The progressive decrease in S/V produced by the latex spheres is consistent with their effect on the L/W ratio. However, the total loss of deformability observed with red cells containing parasites of similar or smaller size cannot be explained on these grounds alone. It suggests an additional mechanism, such as calcium-induced crosslinking of the red cell cytoskeleton.

Erythrocyte Deformability↗

PubMed1991

Accurate determination of mean cell volume by isotope dilution in erythrocyte populations with variable deformability.

Variations in erythrocyte deformability and morphology lead to artifacts in electronic determinations of mean cellular volume (MCV) by the aperture-impedance method. The micropipette-aspiration technique loses accuracy when applied to severely aberrant cells such as dense sickle cells. A new light-scattering technique requires that the cells be capable of undergoing isovolumetric sphering. In contrast, the isotope-dilution (ID) method measures absolute mean volume and is free of artifacts associated with abnormal deformability or morphology. It does not depend on any algorithms or correction factors and does not subject the cells to any stringent processing, not even centrifugation. The ID method can be used to determine the mean volume of red cells in hypo- or hypertonic media or in the presence of pharmacologic agents. It requires no more than a 1-ml aliquot of suspended cells at a hematocrit of at least 30%. The cells can be readily recovered, washed, and reused. Using EDTA labeled with 57Co as an extracellular space marker we have used ID to determine the MCV of fractionated normal human red blood cells (RBC), unfractionated RBC containing SS hemoglobin, and RBC from four other mammalian species. In the case of human RBC obtained from eight normal donors, we obtained mean MCV values (+/- SD) of 83.6 +/- 3.0, 87.5 +/- 3.9, and 76.5 +/- 5.3 fl for unfractionated and top and bottom 10% density fractions, respectively. The value 83.6 is significantly lower than the generally accepted range of 89-91 indicated by electronic analyzers calibrated against spun microhematocrits. The discrepancy of about 7% can account for the difference between mean cell hemoglobin concentration (MCHC) data determined by a calibrated Coulter Counter and corresponding data obtained with paired samples using a cyanmethemoglobin procedure specified in NCCLS Standard H15-A and corrected for trapped plasma.

Anemia, Sickle Cell↗

PubMed1991

Calcium and the malaria parasite: parasite maturation and the loss of red cell deformability.

In the studies reported here, we examined the role of calcium in the maturation of the human malaria parasite Plasmodium falciparum, and in the loss of red cell deformability associated with parasite maturation. P. falciparum alters the permeability of its host red cell, which normally maintains submicromolar cytoplasmic concentrations of calcium. Infection of the red cell and parasite maturation produce a 30-fold increase in calcium uptake. Both parasite maturation and the loss of red cell deformability are blocked by EGTA (by extracellular-free calcium concentrations less than or equal to 35 microM) and by other calcium antagonists. The loss of red cell deformability that occurs with parasite maturation is accompanied by alterations in the cytoskeletal proteins of parasitized red cells similar to those produced by the calcium ionophore A23187 (reductions in bands 2.1 [ankyrin], 4.1, and 5 [actin]). These results establish that parasite development and the loss of red cell deformability are calcium-dependent. They suggest that parasite-induced changes in the calcium permeability of the red cell activate endogenous transglutaminase activity by raising the free calcium concentration of the red cell cytoplasm.

Animals↗

PubMed1991

Intraerythrocytic parasites and red cell deformability: Plasmodium berghei and Babesia microti.

In the studies reported here, we examined the effects of two intraerythrocytic parasites (Plasmodium berghei and Babesia microti) on the deformability of their host red cells. Red cell deformability was assessed by three criteria: 1) the prevalence of tank-treading (the tank-tread-like movement of the red cell membrane around its cytoplasmic contents), 2) elongation under fluid shear stress (the steady-state length: width ratio), and 3) the time required for the red cell to reduce its steady-state elongation by 63.2% after the abrupt release of the shear stress (the characteristic shape-recovery time). Trophozoite-stage parasites of both species reduced the prevalence of tank-treading. Ring- and trophozoite-stage parasites of both species reduced steady-state elongation, and ring-stage P. berghei prolonged the shape-recovery time. These results suggest that altered red cell deformability is a common feature of infection with intraerythrocytic parasites.

Animals↗

PubMed1990

Extensional recovery of an intact erythrocyte from a tank-treading motion.

Normal human erythrocytes suspended in shear flow are stretched into quasi ellipsoidal forms while their membranes rotate smoothly (tank-treading). Following abrupt cessation of shear the cells recover their discoidal shapes approximately exponentially, in the manner of a Kelvin-Voigt (K-V) solid. To test the hypothesis that the recovery process is membrane-controlled, the effects of initial deformation, cytoplasmic viscosity and membrane surface-to-volume ratio were studied. It was concluded that the membrane dynamics dominates the transient shape recovery, and that the characteristic recovery time is dependent on the initial deformation. Hence, the usual simplified analysis based on retraction of a plane sheet of K-V material with constant moduli appears to be an inadequate treatment of transient whole cell recovery.

Biomechanical Phenomena↗

PubMed1989

Mechanisms underlying atriopeptin-induced increases in hematocrit and vascular permeation in rats.

Infusion of atriopeptin into humans and animals induces diuresis, natriuresis, hemodynamic changes, and an increase in arterial hematocrit. The objective of the present study was to elucidate the mechanism(s) responsible for the increase in hematocrit in rats given atriopeptin-24 (AP-24). Infusion of AP-24 for 30 minutes increased large vessel and total vascular hematocrits by 10-15% while decreasing microvascular hematocrits by 9-26% in numerous tissues. Regional vascular permeation by [131I] bovine serum albumin was markedly increased (2-5.6-fold) in many tissues, consistent with a 16% decrease in plasma volume. AP-24 infusion had no effect on extracellular fluid volume or the volume of circulating red cells. Vascular resistance was decreased and was associated with a significant increase in blood flow in many, but not all, tissues. In the atrium and in the small and large intestine the percentage decrease in microvascular hematocrit exceeded the increase in blood flow. These observations indicate that the increase in large vessel hematocrit induced by AP-24 infusion 1) is accompanied by a decrease in (microvascular) hematocrit in many tissues, 2) reflects an increase in overall (i.e., total vascular hematocrit), and 3) is the consequence of a decrease in plasma volume resulting from a marked increase in the rate of vascular permeation by plasma constituents in multiple tissues.

Animals↗

PubMed1989

Myocyte contracture, vascular resistance, and vascular permeability after global ischemia in isolated hearts from alloxan-induced diabetic rabbits.

Coronary vascular hemodynamics, albumin permeation, and myocyte contractility were assessed in isolated hearts from 6-mo alloxan-induced diabetic (ALX-D) rabbits during 3 h of reperfusion after 40 min of global no-flow ischemia. Residue-detection data, generated during the single passage of a bolus of 125I-labeled bovine serum albumin (125I-BSA) through the coronary vasculature, were used to estimate indices of vascular function, including the mean transit time of 125I-BSA, the fractional rate of intravascular clearance of 125I-BSA, and 125I-BSA permeation of coronary vessels. During reflow after ischemia in hearts from control rabbits, vascular resistance increased approximately three times that at baseline, left ventricular end-diastolic pressure (LVEDP) increased 8-10 times, and maximum +dP/dt recovered 0.4 times baseline, whereas the fractional rate of washout of intravascular 125I-BSA decreased to less than one-half of baseline values (was prolonged 2-fold), and albumin permeation and mean-transit time were increased 3 and 5 times baseline, respectively. In hearts from diabetic rabbits, vascular resistance was similar to the control group before ischemia but increased only one-third as much during reflow after ischemia. Increases in LVEDP during reflow were approximately 50% lower than controls, and +dP/dt recovered approximately 2.5 times more than in control hearts. 125I-BSA permeation in diabetics was similar to controls before ischemia, but during reflow increased 6 times (approximately 2 times controls). Washout of intravascular 125I-BSA was prolonged approximately 20% versus baseline during 3 h of reflow in hearts from diabetic rabbits. Thus, ALX-D in the rabbit delayed ischemia-reperfusion injury to myocytes and vascular smooth muscle cells while increasing vascular albumin permeation.

Animals↗

PubMed1989

Deduction of intrinsic mechanical properties of the erythrocyte membrane from observations of tank-treading in the rheoscope.

Measurements of the dimensions and membrane rotational frequency of individual erythrocytes steadily tank-treading in a Rheoscope are used to deduce the surface shear viscosity (eta m) and the shear elastic modulus (mu m) of the membrane. Previously published algorithms (Trans-Son-Tay et al., Biophys. J. 46: 65, 1984, and 51: 915, 1987) plus an assumed area-conserving membrane velocity field (Secomb and Skalak, Q. J. Mech. Appl. Math. XXXV 2: 233, 1982) are applied to calculate eta m as a function of the second invariant of the surface strain rate and mu m as a function of the second invariant of membrane strain. The results indicate density-related increases in membrane stiffness and viscosity, shear-thinning viscous behavior, and strain-stiffening elastic behavior.

Algorithms↗

PubMed1988

Vascular flow resistance in rabbit hearts: "apparent viscosity" of RBC suspensions.

Isovolumically beating, isolated hearts from male New Zealand rabbits were perfused retrograde via the aorta at a paced rate of 180 to 200 beats per minute. Perfusions were effected at arterial pressures (AP) ranging from 10 to 80 mm Hg. Perfusions (Krebs-Henseleit buffer + 1% BSA + insulin, 100 microliters/liter; same + 40% sheep RBC; same + 40% bovine RBC) were dosed with 15 mM papaverine to induce maximum vasodilation. In each case normalized flow rate (per unit heart mass) varied linearly with AP but all linear regressions extrapolated to a positive, zero-flow value of AP. Normalized flow resistance, defined as the slope of the line fitted to the pressure-drop vs normalized flow (per unit of dry heart weight) data, was not affected by the change from sheep to bovine RBC in the maximally dilated hearts. Data from RBC-free perfusions were inserted in Poiseuille's law to compute an effective geometric factor for the organ vasculature. This is turn was used to calculate apparent viscosities of the RBC suspensions. These were indistinguishable for the different RBC suspensions and fell between 0.5 and 0.6 of the respective high shear-rate values measured in a cone-plate viscometer, thus agreeing with the findings of S.R.F. Whittaker and F.R. Winton (1933, J. Physiol. (London) 78, 339-369) for the dog hindlimb.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

A programmable, computer-controlled cone-plate viscometer for the application of pulsatile shear stress to platelet suspensions.

Described is a special purpose cone-plate viscometer that is capable of acceleration or deceleration through a step change in speed in less than 0.7s. The speed of the rotating cone is controlled by a microcomputer which can be programmed to generate speed vs time ramp functions of variable slope. Prior calibration of motor power required to shear Newtonian fluids of known viscosity at various speeds provides the basis for determination of apparent suspension viscosity and enables the viscometer automatically to compensate for changing sample viscosity during shear. The viscometer was used to carry out a series of preliminary studies in which platelet-rich plasma (PRP) was subjected to continuous and pulsatile shear stress at 37 degrees C. Shear-induced platelet aggregation (SIPAG) was significantly greater in response to pulsatile versus continuous shearing except at the lowest applied stress (10 dyn/cm2). Increases ranged from about 40 percent at a stress amplitude of 25 dyn/cm2 to nearly 55 percent at dyn/cm2. This increasing trend with stress amplitude might be interpreted as a positive correlation between SIPAG and the loading rate. Dense granule release, as indicated by serotonin release, was dependent on both stress amplitude and number of pulses even at the higher stress where SIPAG was independent of pulse number.

Blood Platelets↗

PubMed1987

Membrane stress and internal pressure in a red blood cell freely suspended in a shear flow.

Presented is an algorithm for the approximate calculation of the membrane stress distribution and the internal pressure of a steadily tank-treading red cell. The algorithm is based on an idealized ellipsoidal model of the tank-treading cell (Keller, S.R., and R. Skalak, 1982, J. Fluid Mech., 120:27-47) joined with experimental observations of projected length, width, and tank-treading frequency. The results are inexact because the membrane shape and velocity are assumed a priori, rather than being determined via appropriate material constitutive relations for the membrane; these results are, nevertheless, believed to be approximately correct, and show that internal pressure builds up slowly as cell elongation increases, rising more rapidly as the deformed cell approaches the limiting geometry of a prolate ellipsoid. The maximum shear stress resultant in the membrane was found to be below but approaching the yield point range at the highest shear rate applied.

Algorithms↗

PubMed1987

Increased ischemia-reperfusion injury to the heart associated with short-term, diet-induced hypercholesterolemia in rabbits.

The effects of increased dietary cholesterol content on coronary vascular hemodynamics and endothelial cell transport function were assessed in isolated rabbit hearts during 3.5 hours of reperfusion after 30 minutes of global, no-flow ischemia. In control hearts from rabbits fed normal chow, perfusion pressure, left ventricular end-diastolic pressure, maximum +dP/dt, and the rate of intravascular clearance of radiolabelled albumin remained constant during 5 hours of continuous perfusion, while the mean transit time of radiolabelled albumin increased 1.6 X baseline. In ischemic hearts from rabbits fed normal chow, perfusion pressure increased 59% during reperfusion while left ventricular end-diastolic pressure and maximum +dP/dt returned toward control levels. The rate of intravascular clearance of radiolabelled albumin decreased 36%, and the mean transit time of albumin increased approximately 3 X baseline. Ischemia-reperfusion injury to the cardiac vasculature and musculature was markedly increased in hearts of rabbits fed chow supplemented with 2% cholesterol for 2-3 weeks compared to rabbits fed the same diet for a longer duration (5-16 weeks) or rabbits fed normal chow. Prior to ischemia, permeation of the coronary vasculature by albumin was increased twofold in rabbits fed cholesterol for 2-3 weeks while myocyte contractile function was normal relative to chow-fed controls or the group fed cholesterol for 5-16 weeks. These effects of acute cholesterol feeding precede occlusive atherosclerotic coronary artery disease and occur at plasma cholesterol concentrations one third of those in rabbits fed cholesterol for the longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗