RESUMO
Current motion capture techniques all have shortcomings when applied to the 3D quantitative evaluation of thumb base motion. Dynamic CT might overcome these shortcomings but, so far, robustness of this technique in more than one specimen has not yet been demonstrated. The aim of the current study is to further evaluate the use of dynamic CT for quantification of thumb motion in a larger cadaveric study using a protocol which is feasible in a clinical context. A dynamic CT scan was acquired from six cadaveric human forearms, while a motion simulator imposed thumb opposition. After image acquisition and segmentation, carpal bone motion was quantified using helical axes. To enable comparisons between specimens, intersection points of the instantaneous helical axis with an anatomically defined plane were determined. Precision of the dynamic CT method, measured as variation in distances between silicon nitride beads between frames of a dynamic scan, was 0.43mm (+/-0.09mm) when fixed to the skin and 0.13mm (+/-0.04mm) when embedded into the bone. Absolute deviation between known and measured distances were not larger than 0.34mm. We could demonstrate and quantify that thumb opposition is associated with motion at the trapeziometacarpal and scaphotrapezotrapezoidal joints. High consistency in motion patterns between specimen were found, while the radiation dose was limited. We conclude that dynamic CT can be used to visualize and quantify 3D thumb kinematics, making it a promising method to explore kinematics in vivo.
Assuntos
Polegar/fisiologia , Fenômenos Biomecânicos , Ossos do Carpo/diagnóstico por imagem , Ossos do Carpo/fisiologia , Humanos , Movimento/fisiologia , Polegar/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: The respective roles of the dorsoradial (DRL) and anterior oblique (AOL) ligaments in stability of the highly mobile trapeziometacarpal (TMC) joint remain disputed. Earlier publications have pointed to the AOL as the key stabilizing structure; yet, more recent publications have challenged the stabilizing role of the AOL, favoring the DRL as the main TMC joint stabilizer. We executed an anatomical study of the ligaments, including detailed dissection to quantify the length, width, and thickness of the AOL and DRL and tested the material properties of these ligaments. METHODS: Thirteen fresh frozen cadaveric thumbs from 9 specimens were used. Length, width, and thickness of the AOL and DRL were measured on magnetic resonance imaging and/or after dissection. Next, the first metacarpal and trapezium were isolated together with both ligaments, and both bones were cut sagittally to isolate a first metacarpal-AOL-trapezium and first metacarpal-DRL-trapezium complex from each thumb. These samples were subjected to cyclic loading in displacement-controlled tests. The obtained force-displacement curves were used to calculate stiffness and hysteresis of each sample. RESULTS: Our results showed that the DRL is significantly shorter and thicker than the AOL, which is thin and ill-defined. Our results also indicate that the DRL has a higher stiffness than the AOL, making it a more likely candidate to provide joint stability. CONCLUSIONS: Although the AOL has been asserted to be the primary restraint to dorsoradial subluxation, this view has been challenged over the past 10 years by several studies. These studies have shown the AOL to be relatively weak and compliant compared with the intermetacarpal and dorsoradial ligaments and have demonstrated that the DRL is the strongest and stiffest ligament of the TMC joint. Our studies confirm these findings. CLINICAL RELEVANCE: This study indicates that the DRL is relatively stiff and thick, suggesting it should be repaired or reconstructed when disrupted to restore stability of the TMC joint.
Assuntos
Articulações Carpometacarpais/anatomia & histologia , Articulações Carpometacarpais/fisiologia , Ligamentos Articulares/anatomia & histologia , Ligamentos Articulares/fisiologia , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Cadáver , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Metacarpo/anatomia & histologia , Metacarpo/fisiologia , Pessoa de Meia-Idade , Articulação do Punho/anatomia & histologia , Articulação do Punho/fisiologiaRESUMO
Intravenous administration of piracetam to hamsters reduced the formation of a platelet-rich venous thrombus induced by a standardised crush injury, in a dose-dependent fashion with an IC50 of 68 +/- 8 mg/kg. 200 mg/kg piracetam also significantly reduced in vivo thrombus formation in rats. However, in vitro aggregation of rat platelets was only inhibited with piracetam-concentrations at least 10-fold higher than plasma concentrations (6.2 +/- 1.1 mM) obtained in the treated animals. No effects were seen on clotting tests. In vitro human platelet aggregation, induced by a variety of agonists, was inhibited by piracetam, with IC50's of 25-60 mM. The broad inhibition spectrum could be explained by the capacity of piracetam to prevent fibrinogen binding to activated human platelets. Ex vivo aggregations and bleeding times were only minimally affected after administration of 400 mg/kg piracetam i.v. to healthy male volunteers, resulting in peak plasma levels of 5.8 +/- 0.3 mM. A possible antiplatelet effect of piracetam could be due to the documented beneficial effect on red blood cell deformability leading to a putative reduction of ADP release by damaged erythrocytes. However similarly high concentrations were needed to prevent stirring-induced "spontaneous" platelet aggregation in human whole blood. It is concluded that the observed antithrombotic action of piracetam cannot satisfactorily be explained by an isolated direct effect on platelets. An additional influence of piracetam on the rheology of the circulating blood and/or on the vessel wall itself must therefore be taken into consideration.
Assuntos
Fibrinolíticos/uso terapêutico , Piracetam/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Trombose/tratamento farmacológico , Animais , Tempo de Sangramento , Cricetinae , Modelos Animais de Doenças , Fibrinogênio/metabolismo , Humanos , Técnicas In Vitro , Masculino , Contagem de Plaquetas , Ligação Proteica , Ratos , Trombose/metabolismoRESUMO
Numerous clinically relevant animal models exist for thrombosis studies. Few of these are suitable for both arteries and veins. In this investigation, an established venous thrombosis model was adapted through minimal technical adjustments to allow also the study of arterial thrombosis. A standardized subintimal crush injury was performed to carotid arteries or femoral veins of hamsters. Thrombus volumes were then quantified by direct morphometric measurements from serial microscopic sections or by on-line image analysis of light intensity changes from transilluminated vessels. The platelet-rich mural thrombus, which was established within minutes of the trauma, disintegrated during the observation period. The life cycle of the thrombus was different in arteries and veins, but significant linear correlation (p < 0.01) was found in both types of vessel between thrombus volumes measured by the two techniques. The model can consequently be used for comparative in vivo thrombosis studies in small (approximately 1-mm) arteries and veins.
Assuntos
Trombose das Artérias Carótidas/patologia , Veia Femoral , Trombose/patologia , Animais , Artérias Carótidas/patologia , Trombose das Artérias Carótidas/etiologia , Cricetinae , Modelos Animais de Doenças , Veia Femoral/patologia , Masculino , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Trombose/etiologia , TransiluminaçãoRESUMO
After a standardized trauma to carotid arteries or femoral veins of hamsters, the antithrombotic effects of two antiplatelet agents (aspirin and the glycoprotein IIb/IIIa antagonist G4120) and two anticoagulants (heparin and the direct thrombin inhibitor r-hirudin) were studied in vivo. The thrombus area volume was assessed by image analysis of the transilluminated experimental vessels. Heparin, r-hirudin, and G-4120 demonstrated a dose-dependent complete inhibition of arterial and venous thrombosis. In contrast, the antithrombotic effect of aspirin was only partial in both vessel types. A significant correlation between activated partial thromboplastin time (aPTT) at the end of the experiments and the antithrombotic effect was observed with the anticoagulant agents. However, only r-hirudin inhibited thrombus formation at a therapeutical prolongation of aPTT, while heparin required supratherapeutical amounts to achieve the same inhibition. The data confirm that the inhibition of aspirin, heparin, r-hirudin, and G-4120 on the formation of platelet-rich thrombi is independent of the blood flow rate.
Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Trombose das Artérias Carótidas/prevenção & controle , Veia Femoral , Heparina/uso terapêutico , Terapia com Hirudina , Peptídeos Cíclicos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Sulfóxidos/uso terapêutico , Trombose/prevenção & controle , Animais , Trombose das Artérias Carótidas/etiologia , Cricetinae , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Modelos Lineares , Masculino , Tempo de Tromboplastina Parcial , Trombose/etiologiaRESUMO
Platelet aggregation plays an important role in the pathogenesis in arterial thrombotic disorders. The binding of fibrinogen via the Arg-Gly-Asp (RGD) recognition sequence to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor is an essential step of platelet aggregation induced by various physiologic agonists, and RGD-containing peptides that bind to the GPIIb/IIIa receptor inhibit thrombus formation in vivo. L-cysteine, N-(mercaptoacetyl)D-tyrosyl-L-arginylglycyl-L alpha-aspartyl-cyclic (1----5)-sulfide, 5-oxide (G4120), a cyclic RGD-containing synthetic pentapeptide, inhibits adenosine diphosphate (ADP)-induced platelet aggregation with 50% inhibition (IC50) at a concentration of 0.05 microgram/mL in human plasma, 0.12 microgram/mL in hamster plasma, and 11 micrograms/mL in rat plasma. Corresponding values for the linear tetrapeptide Arg-Gly-Asp-Phe (RGDF) were 7 and 100 micrograms/mL in human and hamster plasma. The antithrombotic effects of G4120 and RGDF were evaluated in a hamster model consisting of a mural platelet-rich femoral vein thrombus induced by standardized endothelial cell damage. Bolus intravenous injection of G4120 was followed by a biphasic disappearance of G4120 from plasma with t1/2 alpha of 3.7 minutes and t1/2 beta of 63 minutes, corresponding to a plasma clearance of 5.2 +/- 0.68 mL/min. Bolus intravenous injection of G4120 inhibited ex vivo platelet aggregation with 0.5 mumol/L ADP and in vivo thrombus formation in a dose-dependent manner, with ID50 of 11 and 11 micrograms/kg, respectively. Bolus injection of RGDF inhibited in vivo thrombus formation; 43% inhibition was obtained at a dose of 30 mg/kg. Thus, this hamster platelet-rich femoral vein thrombosis model may be useful for the investigation of the antithrombotic properties of platelet GPIIb/IIIa antagonistic peptides. The cyclic synthetic peptide G4120 appears to have a very potent antithrombotic activity in vivo.
Assuntos
Fibrinolíticos/farmacologia , Peptídeos Cíclicos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Sulfóxidos/farmacologia , Sequência de Aminoácidos , Animais , Cricetinae , Modelos Animais de Doenças , Cães , Veia Femoral , Humanos , Masculino , Dados de Sequência Molecular , Oligopeptídeos/farmacologia , Peptídeos Cíclicos/farmacocinética , Agregação Plaquetária/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , Ratos , Sulfóxidos/farmacocinética , Trombose/tratamento farmacológicoRESUMO
A new in vivo method to study the size and dynamics of a growing mural thrombus was set up in the rat femoral vein. The method uses a standardized crush injury to induce a thrombus, and a newly developed transilluminator combined with digital analysis of video recordings. Thrombi in this model formed rapidly, reaching a maximum size 391 +/- 35 sec following injury, after which they degraded with a half-life of 197 +/- 31 sec. Histological examination indicated that the thrombi consisted mainly of platelets. The quantitative nature of the transillumination technique was demonstrated by simultaneous measurement of the incorporation of 111In labeled platelets into the thrombus. Thrombus formation, studied at 30 min interval in both femoral veins, showed satisfactory reproducibility overall and within a given animal. With this method we were able to induce a thrombus using a clinically relevant injury and to monitor continuously and reproducibly the kinetics of thrombus formation in a vessel of clinically and surgically relevant size.