Plasmodium falciparum maturation abolishes physiologic red cell deformability.

Normal red cells deform markedly as they pass through the spleen and the peripheral capillaries. In these studies, the effects of Plasmodium falciparum infection and maturation on the deformability of parasitized red cells exposed to fluid shear stress in vitro were examined by means of a rheoscope. Red cells containing the early (ring) erythrocytic stage of the parasite have impaired deformability at physiologic shear stresses, and recover their normal shape more slowly. Red cells containing more mature parasites (trophozoites or schizonts) exhibit no deformation under the same conditions. These results provide a mechanism to explain the ability of the spleen to remove parasitized red cells from the circulation of both immune and nonimmune hosts.

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.

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.

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.

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.

Mathematical model of the velocity field external to a tank-treading red cell.

The velocity field external to a stationary ellipsoidal particle with continuously rotating surface motion driven by a surrounding shear flow is calculated. The configuration is intended to model the so-called "tank-treading" behavior of mammalian erythrocytes (red cells) when suspended in shear flow. The boundary-value problem posed is based on the model developed by Keller & Skalak (7) and is solved by adapting Jeffrey's general solution (9) for the Stokes flow about a rigid, freely rotating ellipsoid immersed in an unbounded viscous flow. Streamlines and velocity profiles in the plane of symmetry are obtained by numerical computations. The flow pattern reveals two free stagnation points near the ends of the particle and the streamlines branching from these points delineate a region of closed streamlines surrounding the particle and two recirculating wakes extending to infinity both upstream and downstream of the particle. The presence of the wakes suggests a mechanism for enhanced diffusion of smaller solute particles in the surrounding fluid.

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.

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.

[Acute experimental pancreatitis in the opossum. The role of prior truncular vagotomy on the inflammatory response]. / Pancreatitis aguda experimental en el opossum. Rol de la vagotomía troncular previa en la respuesta inflamatoria.

BACKGROUND: Acute pancreatitis (AP) is a common cause of admission to the emergency room. Its etiopathogeny is poorly understood. The pancreatic inflammatory response in this process is unclear. The influence of the autonomic nervous system is a controversial issue. AIMS: To demonstrate the effects of truncular vagotomy on AP due to duodenal distention in the South American opossum. PLACE OF APPLICATION: Department of experimental surgery (Churruca-Visca Hospital) INEUCI (Neuroscience Institute, CONICET, UBA). POPULATION: Male and female South American opossum divided into: a control group (7 animals); group A: truncular vagotomy and pyloroplasty seven days after the onset of AP (7 animals). Group B: truncular vagotomy and pyloroplasty 30 days after provoking AP (7 animals). Group C: truncular vagotomy and pyloroplasty 45 days after the onset of AP (7 animals). METHODS: Acute pancreatitis was caused by duodenal distention of the second portion by inserting a Foley catheter through a gastrostomy. CONCLUSIONS: The method of provoking AP is original. The influence of autonomous nervous system is being underestimated in most of the literature available.

[Acute pancreatitis of uncommon etiology: a physiopathologic approach]. / Pancreatitis agudas de etiologías poco frecuentes: una aproximación fisiopatogénica.

A review of 73 cases of acute pancreatitis (A.P.) of *A in frequent etiology is critically analyzed. The patients were allocated to the following categories: post ingestion of a large meal, dyslipemic, post ERCP, post operative, pregnancy, and puerperium linked., post urlian parotiditis, post stress, idiopathic, drug associated, post traumatic. In each of the above groups those hypotheses that are currently primarily accepted as been mainly concerned with the etiopathogenesis of the inflammatory episode were given preference. One factor upon which the authors has put special emphasis is that of frequent involvement of the nervous system through different types of autonomic are reflexes. This pathogenic mechanism is surprisingly disregarded in the literature. The interrelation ship between the severity of an AP episode and the background provided by the "pancreon" secretory activity is also emphasized. The mortality rate of the whole series was of 7 cases (9.6%). The groups that disclosed the highest rates were related to abdominal surgery (50%) and to dyslipemia (17%).

Rheoscopic investigation of red cell deformability in sickle cell anemia.

Adequate erythrocyte deformability is crucial to microvascular function. In sickle cell anemia, a significant fraction of the circulating red cells lose deformability and assume highly abnormal shapes when exposed to low plasma oxygen tension (PO2). The loss of deformability is believed to induce blockage of flow in capillaries with consequent painful crisis or organ infarcts. The deformability of sickle erythrocytes at graded levels of PO2 were investigated in the rheoscope, a viscometric device consisting of transparent counter-rotating cone and plate. Quantitative indices of deformability obtained from still photographs and videotape recordings of cells subjected to shear flow were: fraction of all suspended cells capable of deformation, steady-state elongation, and time course of transient shape recovery following abrupt flow cessation. Suspensions of unfractionated cells were first equilibrated against gas mixtures (O2, N2, CO2) with PO2 = 160, 40 or 20 mm Hg at room temperature and then sheared under the same atmosphere. Results obtained with blood samples from ten pediatric patients being treated at St. Louis Children's Hospital show strong donor-to-donor variations and significant impairment of deformability in the unsickled members of the cell populations relative to normal controls.