RESUMO
EXCERPT: During total joint arthroplasty, showers of bony spicules, marrow fat, and clot are carried by venous blood to the lungs, creating conditions not unlike those present in patients who have suffered traumatic long bone fractures. There is recent evidence that, like the fat embolism syndrome (FES), which often has a component of neurologic dysfunction, total joint arthroplasty and femoral nailing are associated with intraoperative brain embolization as determined by transcranial Doppler ultrasonography, and magnetic resonance brain imaging. Although there are good data demonstrating that intraoperative brain embolization occurs during total joint arthroplasties, the makeup and, even more importantly, the clinical significance of these emboli remain speculative. Brain microemboli resulting from cardiac surgery occur by the millions and may cause focal ischemia resulting in significant neurologic dysfunction. Our studies suggest that the major source of these microemboli is lipid droplets of the patient's fat that drip into the blood in the surgical field. This lipid-laden blood is aspirated and then returned to the patient via the cardiopulmonary bypass (CPB) apparatus. Our investigations have focused on the causes (microemboli), consequences (brain damage), and strategies for elimination of brain lipid microemboli resulting from salvaged blood collected during surgery.
Assuntos
Artroplastia de Substituição/efeitos adversos , Perda Sanguínea Cirúrgica , Embolia Gordurosa/etiologia , Embolia e Trombose Intracraniana/etiologia , Animais , Transfusão de Sangue Autóloga/efeitos adversos , Cimentos Ósseos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Circulação Cerebrovascular , Cães , Embolia Gordurosa/prevenção & controle , Humanos , Embolia e Trombose Intracraniana/prevenção & controle , Modelos AnimaisAssuntos
Ponte Cardiopulmonar/efeitos adversos , Transtornos Cerebrovasculares/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Barbitúricos/uso terapêutico , Temperatura Corporal , Ecocardiografia Transesofagiana , Humanos , Embolia e Trombose Intracraniana/prevenção & controle , Nimodipina/uso terapêuticoRESUMO
Non-invasion model for photochemically induced brain infarction was used to study the effect of a the new anti-ischemic drug LB ("Plaferon") in albino rats. Intensity of a local blood flow was measured so as oxygen tension in brain cortex. Square and volume of the disturbed nervous tissue region, capillary length and density of distribution of different caliber vessels were detected by means of light microscopy in serial sections of brain cortex. Preliminary introduction of LB was found to prevent formation of thrombotic infarction (the volume of cortical zone damaged is 85% lower as compared to the control). Anti-ischemic effect of LB implicates in vasodilatory action on cerebral vessels and also breaking pathogenic chain of ischemia development.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Infarto Cerebral/prevenção & controle , Embolia e Trombose Intracraniana/prevenção & controle , Neuropeptídeos/uso terapêutico , Vasodilatadores/uso terapêutico , Animais , Córtex Cerebral/patologia , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Embolia e Trombose Intracraniana/etiologia , Embolia e Trombose Intracraniana/patologia , Fotoquímica , Fármacos Fotossensibilizantes , Ratos , Rosa Bengala , Fatores de TempoRESUMO
Effects of thromboxane A2 (TXA2) synthase inhibitors (CV-4151 and ozagrel) on cerebral thrombosis and cerebral damage were examined in a rat middle cerebral artery (MCA) thrombosis model and their potencies were compared with the conventional antithrombotic agents, aspirin and ticlopidine. CV-4151 significantly inhibited photochemically induced MCA thrombosis by oral (1 and 10 mg/kg) and intravenous (1 mg/kg) administration. Ozagrel (10 mg/kg, p.o.) also inhibited it. The potency of CV-4151 was about 10 times stronger than that of ozagrel, being comparable with the inhibition of blood TXA2 generation. Aspirin (100 mg/kg, p.o.) and ticlopidine (300 mg/kg, p.o.) showed an inhibitory tendency on MCA thrombosis. Twenty-four h after photochemical stimulation, cerebral edema and cerebral infarction were observed, and the lactate content in the brain increased. CV-4151 and ozagrel prevented this edema, and the antiedema effects of the drugs were correlated with the antithrombotic effect on thrombotic MCA occlusion. CV-4151 (10 mg/kg, p.o.), furthermore, significantly reduced the infarct size and inhibited the increase in lactate content. These results indicate that TXA2 synthase inhibitors inhibit cerebral damage by inhibition of MCA occlusion with thrombosis, probably resulting from the inhibition of TXA2 generation, and their effects are superior to those of aspirin and ticlopidine. TXA2 might play an important role in cerebral damage in the MCA thrombosis model. CV-4151 might be a useful drug for the treatment of cerebral thrombosis and for the prevention of cerebral infarction.
Assuntos
Ácidos Graxos Monoinsaturados/uso terapêutico , Fibrinolíticos/uso terapêutico , Embolia e Trombose Intracraniana/prevenção & controle , Piridinas/uso terapêutico , Tromboxano A2/antagonistas & inibidores , Animais , Aspirina/farmacologia , Aspirina/uso terapêutico , Química Encefálica , Edema Encefálico/prevenção & controle , Artérias Cerebrais , Infarto Cerebral/patologia , Infarto Cerebral/prevenção & controle , Avaliação Pré-Clínica de Medicamentos , Ácidos Graxos Monoinsaturados/farmacologia , Fibrinolíticos/farmacologia , Cobaias , Embolia e Trombose Intracraniana/induzido quimicamente , Embolia e Trombose Intracraniana/tratamento farmacológico , Lactatos/análise , Ácido Láctico , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Metacrilatos/farmacologia , Metacrilatos/uso terapêutico , Fotoquímica , Potássio/análise , Piridinas/farmacologia , Coelhos , Ratos , Ratos Sprague-Dawley , Rosa Bengala/efeitos da radiação , Rosa Bengala/toxicidade , Sódio/análise , Ticlopidina/farmacologia , Ticlopidina/uso terapêuticoRESUMO
We investigated the effect of dietary docosahexaenoic acid (DHA) supplementation on the thrombolytic efficacy of recombinant tissue-type plasminogen activator (rt-PA), platelet aggregability, serum cholesterol and phospholipids. Male Wistar rats (6 weeks old) received dietary DHA supplementation (300 mg/kg per day) for 8 weeks. The rat middle cerebral artery (MCA) was occluded by a thrombus induced by photochemical reaction between rose bengal and green light which cause endothelial damage followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of photochemical reaction. The MCA blood flow was monitored using a laser Doppler flowmeter. rt-PA was administered 30 min after the middle cerebral artery had been occluded by a thrombus. This regimen produced a significant (P < 0.05) decrease in serum free-cholesterol and phospholipids levels, inhibited platelet aggregation ex-vivo induced by collagen in whole blood (P < 0.05), reduced thromboxane (TX) B2 formation (P < 0.01) in whole blood and prolonged the time for thrombotic MCA occlusion (P < 0.01) as compared with values obtained from animals on standard diet. Further, dietary DHA enhanced thrombolytic efficacy of rt-PA and reduced the size of ischaemic cerebral lesions. Our findings suggest that dietary DHA produces antithrombotic effects via metabolic conversion to non-atherogenic and non-platelet stimulant metabolites.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Isquemia Encefálica/prevenção & controle , Ácidos Docosa-Hexaenoicos/uso terapêutico , Embolia e Trombose Intracraniana/prevenção & controle , Administração Oral , Animais , Isquemia Encefálica/etiologia , Circulação Cerebrovascular/efeitos dos fármacos , Colesterol/sangue , Dieta , Ácidos Docosa-Hexaenoicos/administração & dosagem , Endotélio Vascular/lesões , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Embolia e Trombose Intracraniana/sangue , Embolia e Trombose Intracraniana/induzido quimicamente , Luz , Masculino , Fosfolipídeos/sangue , Fotoquímica , Agregação Plaquetária/efeitos dos fármacos , Ratos , Ratos Wistar , Proteínas Recombinantes/uso terapêutico , Rosa Bengala/efeitos da radiação , Rosa Bengala/toxicidade , Método Simples-Cego , Terapia Trombolítica , Tromboxano B2/sangue , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
BACKGROUND AND PURPOSE: Aspirin treatment is recognized as an advantageous adjunct to thrombolytic agents in myocardial infarct patients. In this study we examined the effects of aspirin on the rate of clot lysis and on the frequency and extent of hemorrhagic transformations in rabbit models of embolic stroke. METHODS: Rabbit models of ex vivo platelet aggregation and cutaneous template bleeding times were used to show the anticoagulant effects of aspirin in our experimental paradigm. We monitored tissue-type plasminogen activator (TPA)-induced clot lysis in two rabbit models of embolic stroke by (1) scintigraphically following the dissolution of a 99mTc-tagged clot or (2) using roentgenography to follow the disappearance of an Sn-tagged clot. RESULTS: In animals pretreated (18 hours) with a single administration of aspirin (1, 5, or 20 mg/kg IV) or 1 mg/kg per day for 3 days, the aggregation response of platelets to collagen (3.3 micrograms/mL) or arachidonic acid (0.5 mmol/L) was attenuated. High-dose aspirin also increased ear template bleeding time from 1.6 to 2.6 minutes. When aspirin (20 mg/kg) was administered 18 hours before embolism and subsequent lysis with TPA (0.3 mg/kg bolus; 3 mg/kg per hour IV), the pretreatment significantly antagonized the rate and extent of TPA-induced clot lysis by up to 70%. This was confirmed in a second embolic stroke model. The suppression of TPA-induced lysis was reversed by administration of the prostacyclin analogue iloprost (10 micrograms/kg per hour) directly into the cerebral circulation. CONCLUSIONS: We conclude that aspirin reduces the effects of TPA in embolic stroke models. This effect may be the result of a loss of endothelial prostacyclin production since the effect is reversed by iloprost.
Assuntos
Aspirina/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Embolia e Trombose Intracraniana/prevenção & controle , Animais , Aspirina/administração & dosagem , Tempo de Sangramento , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/fisiopatologia , Modelos Animais de Doenças , Injeções Intravenosas , Embolia e Trombose Intracraniana/sangue , Embolia e Trombose Intracraniana/fisiopatologia , Masculino , Agregação Plaquetária/efeitos dos fármacos , Pré-Medicação , Coelhos , Cintilografia , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/farmacologiaAssuntos
Aspirina/uso terapêutico , Embolia e Trombose Intracraniana/prevenção & controle , Poliéster Sulfúrico de Pentosana/uso terapêutico , Polissacarídeos/uso terapêutico , Idoso , Ensaios Clínicos como Assunto , Feminino , Humanos , Ataque Isquêmico Transitório/prevenção & controle , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , RecidivaRESUMO
One day during an aneurysm surgery under the preoperative administration of mannitol, the feeding artery was accidentally occluded temporarily. Since then, investigation on whether or not mannitol can prevent infarctions in ischemic brain tissues have been carried out utilizing the thalamus infarction model in dogs. Twenty dogs were divided into equal groups, the control and the mannitol group. Temporary clipping for sixty minutes was adopted as a standard for both groups. The only difference between the groups was the administration of 2 g/kg of mannitol before the arterial occlusions. In the control, six of ten dogs showed infarctions verified as histological changes on the seventh post-ischemic day. In the mannitol group only one of ten showed infarction. Each of the difference is statistically significant (P less than 0.03).
Assuntos
Embolia e Trombose Intracraniana/prevenção & controle , Manitol/uso terapêutico , Tálamo/irrigação sanguínea , Animais , Cães , EletroencefalografiaRESUMO
Whether or not mannitol can prevent infarctions in ischemic brain tissues was investigated utilizing the thalamic infarction model in dogs. Twenty dogs were divided into equal control and mannitol treatment groups. Temporary 4 vessel clipping for 60 minutes was adopted as the standard procedure for both groups. The only difference between the groups was the administration of 2 g/kg of mannitol before the arterial occlusion. In the controls, 6 of 10 dogs showed infarctions verified by histological changes at the seventh post-ischemic day. In the mannitol group only 1 dog in 10 showed infarction. The difference is statistically significant.