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Biomedical subjects

L F Mockros

Publications and source records attributed to L F Mockros.

At least 19 recordsLinked to original sources
PubMed1999

Structural origins of fibrin clot rheology.

The origins of clot rheological behavior associated with network morphology and factor XIIIa-induced cross-linking were studied in fibrin clots. Network morphology was manipulated by varying the concentrations of fibrinogen, thrombin, and calcium ion, and cross-linking was controlled by a synthetic, active-center inhibitor of FXIIIa. Quantitative measurements of network features (fiber lengths, fiber diameters, and fiber and branching densities) were made by analyzing computerized three-dimensional models constructed from stereo pairs of scanning electron micrographs. Large fiber diameters and lengths were established only when branching was minimal, and increases in fiber length were generally associated with increases in fiber diameter. Junctions at which three fibers joined were the dominant branchpoint type. Viscoelastic properties of the clots were measured with a rheometer and were correlated with structural features of the networks. At constant fibrinogen but varying thrombin and calcium concentrations, maximal rigidities were established in samples (both cross-linked and noncross-linked) which displayed a balance between large fiber sizes and great branching. Clot rigidity was also enhanced by increasing fiber and branchpoint densities at greater fibrinogen concentrations. Network morphology is only minimally altered by the FXIIIa-catalyzed cross-linking reaction, which seems to augment clot rigidity most likely by the stiffening of existing fibers.

Blood Coagulation↗
PubMed1999

Influence of a natural and a synthetic inhibitor of factor XIIIa on fibrin clot rheology.

We investigated the origins of greater clot rigidity associated with FXIIIa-dependent cross-linking. Fibrin clots were examined in which cross-linking was controlled through the use of two inhibitors: a highly specific active-center-directed synthetic inhibitor of FXIIIa, 1,3-dimethyl-4,5-diphenyl-2[2(oxopropyl)thio]imidazolium trifluoromethylsulfonate, and a patient-derived immunoglobulin directed mainly against the thrombin-activated catalytic A subunits of thrombin-activated FXIII. Cross-linked fibrin chains were identified and quantified by one- and two-dimensional gel electrophoresis and immunostaining with antibodies specific for the alpha- and gamma-chains of fibrin. Gamma-dimers, gamma-multimers, alpha(n)-polymers, and alpha(p)gamma(q)-hybrids were detected. The synthetic inhibitor was highly effective in preventing the production of all cross-linked species. In contrast, the autoimmune antibody of the patient caused primarily an inhibition of alpha-chain cross-linking. Clot rigidities (storage moduli, G') were measured with a cone and plate rheometer and correlated with the distributions of the various cross-linked species found in the clots. Our findings indicate that the FXIIIa-induced dimeric cross-linking of gamma-chains by itself is not sufficient to stiffen the fibrin networks. Instead, the augmentation of clot rigidity was more strongly correlated with the formation of gamma-multimers, alpha(n)-polymers, and alpha(p)gamma(q)-hybrid cross-links. A mechanism is proposed to explain how these cross-linked species may enhance clot rigidity.

Biomechanical Phenomena↗
PubMed1999

Partial prevention of monocyte and granulocyte activation in experimental vein grafts by using a biomechanical engineering approach.

Leukocytes interact with endothelial cells and contribute to the development of vascular diseases such as thrombosis and atherosclerosis. These processes are possibly influenced by mechanical factors. This study focused on the role of mechanical stretch in the activation of monocytes and granulocytes in experimental vein grafts. Two models were created by using rats: a nonengineered vein graft with increased tensile stress, which was created by grafting a jugular vein into the abdominal aorta, and an engineered vein graft with reduced tensile stress, which was created by restricting the vein graft into a cylindrical sheath constructed by using fixative-treated intestinal tissue. The density of activated monocytes and granulocytes, which attached to the endothelium, and the distribution of the intercellular adhesion molecule (ICAM)-1 in endothelial cells were examined using immunohistological assays. It was found that, in nonengineered vein grafts, the density of activated monocytes and granulocytes increased significantly compared to that in normal jugular veins at day 1, 5, 10 and 20. At each observation time, the cell density in the proximal region of the nonengineered vein grafts was significantly higher than that in the middle and distal regions, and the cell density in the distal region was significantly higher than that in the middle region. These changes were associated with ICAM-1 clustering at day 1 and 5 and focal ICAM-1 un-regulation at day 10 and 20. In engineered vein grafts, the density of activated monocytes and granulocytes decreased significantly compared to that in nonengineered vein grafts at all observation times, although it was significantly higher than that in normal jugular veins. At each observation time, the cell density in the proximal and distal regions was significantly higher than that in the middle region, but no significant difference was found between the proximal and distal regions. ICAM-1 clustering along endothelial cell borders was found at day 1 and 5, but no apparent focal ICAM-1 up-regulation was found at day 10 and 20. These results suggested that mechanical stretch due to exposure to increased tensile stress contributed to the activation of monocytes and granulocytes in experimental vein grafts, and this event could be partially prevented by reducing tensile stress using a biomechanical engineering approach.

Analysis of Variance↗
PubMed1997

In vitro identification of angioplasty-induced injury by use of vascular acoustic emissions.

BACKGROUND: We have developed a novel method of diagnosing stress-induced vascular injury. This approach uses the sound energy released from atherosclerotic arterial tissue during in vitro balloon angioplasty to characterize type and severity of induced trauma. METHODS AND RESULTS: Thirty-two postmortem human peripheral arterial specimens 1.0 cm long were subjected to in vitro balloon angioplasty with simultaneous acoustic emission monitoring. Specimens were examined before and after angioplasty to ascertain the extent of angioplasty-induced injury. Gross observation was used to identify dissection. A three-dimensional intravascular ultrasound reconstruction technique was used to estimate the luminal surface area of the specimen. Change in luminal surface area (postangioplasty minus preangioplasty) was used to quantify induced injury. The energy content and spectral distribution of the digitally acquired vascular acoustic emission (VAE) signals were computed. Comparisons of angioplasty-induced trauma with VAE signal characteristics were made. Dissection (mural laceration of variable depth) was observed in 15 of 32 specimens. Eleven showed no evidence of induced dissection, and 6 had preexisting intimal disruptions. The energy content of the VAE signals collected from specimens with dissection was greater than that obtained from those in which dissection was absent: 845 +/- 89.4 mJ (mean +/- SEM; n = 15) versus 128 +/- 40.8 mJ (n = 1 l; P < .001). Comparison of induced trauma and VAE signal energy demonstrated a proportional relationship (r = .87, P < .001, n = 32). CONCLUSIONS: VAE signals contain information characterizing type and severity of angioplasty-induced arterial injury. Because vascular injury is related to adverse procedural outcome, development of VAE technology as an adjunct to conventional diagnostic modalities may facilitate optimal balloon angioplasty delivery and postprocedural care.

Analysis of Variance↗
PubMed1994

Computer-assisted design of an implantable, intrathoracic artificial lung.

A semiempirical mathematical model of convective oxygen transport is used to design a new, low pressure loss, implantable artificial lung that could be used as a bridge to lung transplantation in patients with advanced respiratory failure. The mass transfer and flow friction relations pertinent to the design of a cross-flow hollow fiber membrane lung are described. The artificial lung is designed to transfer over 200 ml/min of oxygen at blood flow rates up to 5 L/min. A compact design and a blood-side pressure loss of < 15 mm Hg allows the device to be implanted in the left chest without the need for a prosthetic blood pump. Surgical implantation of the artificial lung would require the creation of inflow and outflow anastomoses. Oxygen would be supplied via an external source. Blood properties, operating conditions, and empirically determined mass transfer and flow properties are all specified and input into a computer program that numerically solves the design equations. Computer-generated values for the device frontal area, blood path length, and fiber surface area are thereby obtained. The use of this computer-assisted design minimizes the need for extensive trial-and-error testing of prototype devices. Results from in vitro tests of a prototype implantable lung indicate that the mathematical model we describe is an accurate and useful tool in the design of hollow fiber artificial lungs.

Algorithms↗
PubMed1990

An analysis of pollutant gas transport and absorption in pulmonary airways.

A mathematical model of ozone absorption, or for any soluble gas that has similar transport properties, is developed for a branching network of liquid-lined cylinders. In particular, we investigate specific flow regimes for finite length tubes where boundary layer phenomena and entrance effects exist in high Reynolds and Peclet (Pe) number airways. The smaller airways which have lower Reynolds and Peclet number flows are modelled by incorporating the detailed analysis found in [10] and modifying it for airways which have alveolated surfaces. We also consider a reacting gas and treat specific regimes where the reaction front is located at the air-liquid interface, within the liquid or at the liquid-tissue interface. Asymptotic methods are used in regions of the tracheobronchial tree where Pe much less than 1 and Pe much greater than 1. In addition, the fact that the radial transport parameter gamma much less than 1 for this toxin, and others such as nitrous oxides, is employed to simplify the analysis. The ozone concentrations, airway absorption and tissue dose are examined as a function of airway generation for several values of the governing parameters. The general result is a maximal dosing in airway generations 17 to 18 that is much larger (up to an order of magnitude) than the predictions of previous theories.

Absorption↗
PubMed1987

Thrombelastography of blood from subjects with chronic renal failure.

Blood samples from 23 subjects with chronic renal failure and 19 controls were tested using thrombelastography and other hematologic tests. The uremic subjects were divided into two groups, those who had not yet begun maintenance hemodialysis treatments (12 subjects) and those who had (11 subjects). Compared to those from control subjects, the thrombelastograms from the uremic subjects consistently indicate normal clotting times but significantly elevated amplitudes. The increased amplitudes correlate positively in the dialyzed uremic group with both platelet count and fibrinogen concentration and correlate negatively in both uremic groups with hematocrit. Thrombelastography demonstrates a hypercoagulability in these samples in vitro, despite the prolonged bleeding time that commonly occurs in uremic subjects.

Fibrinogen↗
PubMed1986

Mass transfer to fluids flowing through rotating nonaligned straight tubes.

Relatively inefficient heat/mass transfer is characteristic of tubular devices if the Reynolds number is low. One method of improving the heat/mass transfer efficiency of such devices is by inducing transverse laminar secondary circulations that are superimposed on the primary flow field; the resulting transverse velocity components lead to fluid mixing and hence augmented mass transfer in the tube lumen. The present work is a theoretical and experimental investigation of the enhanced transport in rotating, nonaligned, straight tubes, a method of transport enhancement that utilizes Coriolis acceleration to create transverse fluid mixing. This technique couples the transport advantages of coiled tubes with the design advantages of straight tubes. The overall mass balance equation is numerically solved for transfer into fluids flowing steadily through rotating nonaligned straight tubes. This solution, for small Coriolis disturbances, incorporates a third order perturbation solution for the primary and secondary flow fields. For sufficiently small Coriolis disturbances the bulk concentration increase is found to be uniquely determined by the value of a single similarity parameter. As the Coriolis disturbance is increased, however, two additional parameters are required to accurately characterize the mass transfer. In general, increasing the Coriolis accelerations results in an increase in mass transfer. There are solution regimens, however, in which increasing this acceleration can lead to a decrease in mass transfer efficiency. This interesting phenomena, which has important design implications, appears to result from velocity-weighting effects on the exiting sample. Experiments, involving the measurement of oxygen transferred into water and blood, produced data that agree with the theoretical predictions.

Biomechanical Phenomena↗
PubMed1985

Transducer system for the noninvasive recording of arterial pressure contours.

A transducer system is described that permits noninvasive recordings of the pressure-vs-time arterial profile at any palpable site on the body. A thin (30 microns) piezoelectric polymer film of polyvinylidene fluoride serves as the active element and as the mechanical coupler to the skin. The system has high frequency response and a low frequency cut-off of 0.16 Hz. The active element and its support provides a good mechanical impedance match with the skin. The transducer housing resembles a thick wrist watch and is strapped in place. The complete system is designed to record as many as four simultaneous profiles on a subject. Comparisons of the noninvasive transducer records with records taken with an indwelling catheter indicate congruence of the two signals and the first and second derivatives of the two signals, both when the transducer is applied directly to the skin and when a layer of fat is interposed between the skin and the transducer. The system provides a simple atraumatic means of periodically screening and/or monitoring cardiovascular changes in large populations of subjects and would provide a means of tracking changes induced by therapeutic programs.

Arteriosclerosis↗
PubMed1983

The effects of prostacyclin on the coagulation of whole blood.

The effects of prostacyclin (PGI2) on mechanical properties of forming clots were investigated by testing human blood samples on a Thrombelastograph. Concentrations greater than 50 ng/ml (blood) caused a biphasic development of clot stiffness. During the first phase, PGI2 partially inhibited the platelet involvement in coagulation causing initial clot formation at a normal time but with reduced clot stiffness. The second phase occurred after neutralization of PGI2 activity and was characterized by recovery of platelet activity to produce a final clot with normal shear modulus. The duration of the inhibitory effects depended on PGI2 concentration and hematocrit. With a normal hematocrit, a PGI2 concentration of 60 ng/ml caused an inhibition for about 40 min whereas a concentration of 100 ng/ml caused inhibition for about 75 min.

Blood Coagulation↗
PubMed1982

Effect of pulsatility on oxygen transport to the human arterial wall.

Oxygen transfer in fully-developed, pulsating, laminar flow in rigid and distensible tubes was simulated as part of a study of vessel-wall hypoxia and atherogenesis. The model used for the computations is based on dimensions and flows in the human thoracic aorta. The pulsatile velocity fields employed are based on those of Womersley with the modification that the radial convection is written relative to the moving wall. Womersley-type pulsatility, superposed on an axial Poiseuille flow, was found to negligibly affect oxygen transport to the wall. Caution should be exercised, however, in extending this conclusion to the complex pulsatility in actual living vessels.

Aorta, Thoracic↗
PubMed1978

Effect of platelet count and hematocrit on the coagulability of heparinized blood.

The coagulability of heparinized blood is shown to be a function of platelet and red cell concentrations. Thrombelastrographic tests were conducted on celite-activated fabricated whole blood samples with heparin concentrations ranging from zero to 1.46 units per ml of plasma, hematocrits from zero to 50% and platelet counts from zero to 300,000/mm3. The thrombelastograph provides three useful parameters of coagulability in native and heparinized blood: clot time, rate of clot stiffening and final clot stiffness. Of these, only the clot time is determined with the common clotting tests, while the rate and final clot stiffness are measures of clot quality that are found to be particularly sensitive to thrombocytopenia. The test results indicate (i) increases of platelet concentration produce the expected decrease in clot time, increase in rate of stiffening, and increase in final stiffness; (ii) increases of the red cell concentration from zero to 20% hematocrit, produce nonlinear increases in clotability, while further increases beyond 20% hematocrit produce no additional effects if the heparin concentration is less than 1.2 units/ml. Quantative relations are derived between the thrombelastographic variables, heparin concentration, and platelet concentration for those samples with hematocrits greater than 20%. These data indicate further experiments for the study of possible interaction between cellular blood elements and heparin.

Animals↗