Biomedical subjects

C R Wilhelm

Publications and source records attributed to C R Wilhelm.

5 recordsLinked to original sources

PubMed2000

Modeling flow effects on thrombotic deposition in a membrane oxygenator.

The hypothesis that regions of low blood velocity in a membrane oxygenator, as predicted by computational fluid dynamics (CFD), would correspond with regions of clinical thrombotic deposition was investigated. Twenty heparin-coated oxygenators were sectioned following use in adult extracorporeal membrane oxygenation. The activated clotting time (ACT) was maintained at approximately 180 s via heparin infusion throughout the support period. Cross-sections were systematically photographed, and slides made to allow image projection upon a digitizing pad. Thrombotic deposition was traced to allow creation of a device cross-section image with an overlaid color scale representing thrombotic deposition frequency. A two-dimensional CFD model was developed to predict blood velocities throughout the oxygenator cross-section. Direct spatial comparisons were made between maps of CFD modeled blood speed and thrombotic deposition. Theoretical oxygenator design modification was performed within the CFD model to investigate flow paths which might minimize regions of low blood velocity. CFD results demonstrated that low velocity regions qualitatively matched regions with a high incidence of thrombotic deposition. Thrombotic deposition was also correlated to longer perfusion periods. This technique of coupling clinical data and CFD offers the potential to relate flow characteristics to thrombotic deposition and represents a potentially powerful new methodology for the optimization of oxygenator flow-related biocompatibility.

Adult↗

PubMed2000

Cocaine activates platelets and increases the formation of circulating platelet containing microaggregates in humans.

OBJECTIVE: To determine whether there is evidence of platelet activation following in vivo cocaine administration in humans, as cocaine abuse is associated with myocardial infarction and stroke, and platelet activation leading to thrombosis is a possible mechanism. SETTING: University hospital. DESIGN AND SUBJECTS: Following a randomised, double blind crossover design, 14 healthy volunteers were studied twice, receiving cocaine (2 mg/kg intranasally) once and placebo once. Flow cytometric analysis of P-selectin expression (an alpha granule membrane protein found on the surface of activated platelets), quantification of the platelet specific proteins platelet factor 4 and beta thromboglobulin, and measurement of platelet containing microaggregate and platelet microparticle (fragment) formation were used to assess platelet activation. Circulating von Willebrand factor antigen (vWF) was measured to evaluate a possible role of endothelial stimulation concurrent with platelet activation. RESULTS: There was an increase in both platelet factor 4 (mean (SD), 16 (7) to 39 (22) IU/ml, p = 0. 04) and beta thromboglobulin (70 (20) to 98 (26) IU/ml, p < 0.01) at 120 minutes following cocaine administration. Platelet containing microaggregate formation was increased at 40 minutes (from 47 (3.2)% to 54 (2.0)%, p < 0.001) and 80 minutes (55 (2.5)%, p = 0.04). Bleeding time decreased following cocaine from 10 (1) to 9 (1) minutes (p = 0.07). No changes in any of the measured variables were noted following placebo administration. CONCLUSIONS: Cocaine exposure causes platelet activation, alpha granule release, and platelet containing microaggregate formation. These data support the view that cocaine, even at the relatively low doses commonly self administered by occasional abusers, may promote thrombosis and predispose healthy individuals to ischaemic events. Platelet inhibitors should be considered early in any patient with suspected cocaine related ischaemia.

Adult↗

PubMed2000

Blood biocompatibility analysis in the setting of ventricular assist devices.

Ventricular assist devices (VADs) are increasingly applied to support patients with advanced cardiac failure. While the benefit of VADs in supporting this patient group is clear, substantial morbidity and mortality occur during the VAD implant period due to thromboembolic and infective complications. Efforts at the University of Pittsburgh aimed at evaluating the blood biocompatibility of VADs in the clinical, animal, and in vitro setting over the past decade are summarized. Emphasis is placed on understanding the mechanisms of thrombosis and thromboembolism associated with these devices.

Biocompatible Materials↗

PubMed1999

Measurement of hemostatic indexes in conjunction with transcranial doppler sonography in patients with ventricular assist devices.

BACKGROUND AND PURPOSE: Clinical thromboembolism (TE) remains an impediment to the chronic application of ventricular assist devices (VADs). Microembolic signals (MES) have been detected by transcranial Doppler ultrasound (TCD) in patients with VADs, although their origin and relation to TE remain undefined. We have investigated the hypothesis that hemostatic alterations are related to MES and that MES are associated with TE in a group of 27 VAD patients. METHODS: Indexes of coagulation, fibrinolysis, and cellular activation and aggregation were measured before and during the VAD implantation period in conjunction with TCD. Groups were defined on the basis of presence of MES, degree of MES showering, and incidence of TE. RESULTS: MES were observed in 67 (58%) of 115 of individual postoperative TCD measurements and in 21 (78%) of 27 patients. Of patients with TE, 10 (83%) of 12 had detectable MES compared with 11 (73%) of 15 patients without TE (P=0.66). MES were significantly associated with elevated thrombin generation during the implantation period, as reflected by plasma prothrombin fragment F1.2. Elevations in indexes of coagulation, platelet activation, and fibrinolysis relative to normal control subjects were found for patients with VADs with and without detected MES. CONCLUSIONS: Although no significant relation between MES and TE in VAD patients was found, the data support the hypothesis that MES are related to increased hemostatic activity in this patient group despite aggressive anticoagulant therapy.

Adolescent↗

PubMed1998

Monocyte tissue factor expression and ongoing complement generation in ventricular assist device patients.

BACKGROUND: Ongoing complement activation in patients with a ventricular assist device may contribute to observed hemostatic abnormalities and cellular aggregation by mediating leukocyte and platelet activation, formation of leukocyte-platelet conjugates, and the tissue factor pathway of coagulation. METHODS: Blood from 30 patients was collected before ventricular assist device implantation and during the implantation period. Plasma levels of thrombin-antithrombin III complexes, C3a, and SC5b-9 were measured by commercial enzyme-linked immunosorbent assay. Flow cytometry was used to measure circulating monocyte tissue factor expression and circulating monocyteplatelet and granulocyte-platelet conjugates. RESULTS: Thrombin-antithrombin III complex level and monocyte tissue factor expression peaked in the early postoperative period, with maxima occurring on postoperative days 5 and 3, respectively. Levels of C3a and SC5b-9 remained dramatically elevated over normal values for the duration of the study (6 and 5 times upper normal, respectively). Levels of monocyte-platelet conjugates were normal before implantation, decreased during the first 4 postoperative days, and then increased and remained elevated. Levels of granulocyte-platelet conjugates were elevated over the normal range before implantation and remained elevated from postoperative days 3 to 21. A positive correlation was found between levels of SC5b-9 and granulocyte-platelet conjugates (Spearman R=0.66; p < 0.001), and between levels of C3a and thrombin-antithrombin III complex (Spearman R=0.13; p=0.021). CONCLUSIONS: The data suggest a model in which complement mediates formation of leukocyte-platelet aggregates and may indirectly contribute to thrombin generation through monocyte tissue factor expression.

Adult↗