RESUMO
The effect of a selective thrombin inhibitor, (2R, 4R)-4-methyl-1-[N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]- L-arginyl]-2-piperidinecarboxylic acid (MCI-9038), on the fibrinolysis induced by t-PA and u-PA was studied in vitro and in vivo. MCI-9038 remarkably reduced the lysis time of the plasma clot generated by the addition of calcium chloride to the plasma at the concentration ranging from 0.01 to 0.3 microM. Heparin also reduced the plasma clot lysis time with a lower effect than MCI-9038. The fibrin crosslinkage in the plasma clot was inhibited by MCI-9038 or heparin. MCI-9038 potently inhibited the factor XIIIa generation from factor XIII by thrombin. The effect on the in vivo thrombolysis was studied on the arterial thrombosis generated by the endothelial cell injury of the rabbit carotid artery by acetic acid. t-PA dissolved the thrombi with the infusion at 0.96 mg/kg over 2 h without a significant activation of a systemic fibrinolysis. u-PA dissolved the thrombi with the infusion at 180,000 and 360,000 IU/kg over 2 h. At a dose of 0.48 mg/kg t-PA or 90,000 IU/kg u-PA, the thrombi were not dissolved, but the combined use of MCI-9038 at 1.2 mg/kg over 2 h effectively dissolved the thrombi. Thus, combination of MCI-9038 with plasminogen activators accelerated thrombolysis of an experimental thrombosis in rabbits.
Assuntos
Fibrinólise/efeitos dos fármacos , Trombina/antagonistas & inibidores , Animais , Cloreto de Cálcio/farmacologia , Fator XIII/metabolismo , Fibrina/metabolismo , Heparina/farmacologia , Humanos , Cinética , Ativadores de Plasminogênio/metabolismo , Coelhos , Trombose/sangue , TransglutaminasesRESUMO
We studied the precise role of the fracture haematoma in healing by the experimental transplantation of the haematoma at two days and four days after fracture of the rat femur to subperiosteal and intramuscular sites. We used bone marrow and peripheral blood haematomas for control experiments. The transplanted two-day fracture haematoma produced new bone by endochondral ossification at the subperiosteal site, but not at the intramuscular site. Four-day fracture haematoma produced new bone formation at both subperiosteal and intramuscular sites. These results suggest that fracture haematoma has an inherent osteogenetic potential.
Assuntos
Fraturas Ósseas/fisiopatologia , Hematoma/fisiopatologia , Osteogênese/fisiologia , Animais , Fraturas Ósseas/patologia , Hematoma/patologia , Masculino , Músculos/cirurgia , Periósteo/cirurgia , Ratos , Ratos Endogâmicos , Transplante de Tecidos , Cicatrização/fisiologiaRESUMO
Electrophysiological and muscle histochemical studies of denervated muscle were performed simultaneously in order to determine the relationship between fibrillation potentials and muscle fiber type. Fibrillation potentials recorded in the soleus muscle 2 weeks after resection of the sciatic nerve revealed a lower firing rate than in the extensor digitorum longus (EDL) muscle of the same rats. The majority of muscle fibers stained for adenosine triphosphatase (ATPase) activity after preincubation at pH 9.4, 4.6, and 4.3 in the soleus muscle were type 1 fibers, while most of those in the EDL were of type 2. Moreover, one of the rats, which demonstrated no fibrillation potentials in the soleus muscle, was found to have no type 2A or 2B fibers histochemically, in the same soleus muscle. These findings suggest that fibrillation potentials may not originate in type 1 fibers.
Assuntos
Músculos/fisiologia , Potenciais de Ação/fisiologia , Animais , Eletromiografia , Masculino , Denervação Muscular , Músculos/citologia , RatosAssuntos
Fraturas Ósseas , Hematoma , Osteogênese , Cicatrização , Animais , Fraturas Ósseas/patologia , Hematoma/patologia , Masculino , Osso Parietal , Periósteo , Ratos , Ratos EndogâmicosAssuntos
Infarto do Miocárdio/complicações , Obstrução do Fluxo Ventricular Externo/complicações , Idoso , Cateterismo Cardíaco , Ecocardiografia , Feminino , Sopros Cardíacos/diagnóstico , Sopros Cardíacos/diagnóstico por imagem , Humanos , Infarto do Miocárdio/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagemRESUMO
We attempted induction of the conflict behavior by the locus pattern, thumping and conditioning under hypothalamic stimulation in rabbits. Flight was classified as continuous and non-continuous. Thumping was elicited post stimulus. Conditioning responses were obtained during the autonomic-somatic responses, continuous run and non-continuous run. All drugs were administrated orally. Dosage of each drug used in this experiment was calculated by determining the dosage which caused the same degree of muscle relaxation and sedative action in mice (see, Fig. 1) or general behavior in rabbits. Diazepam 5 mg/kg, chlordiazepoxide 10 mg/kg and nitrazepam 1 mg/kg caused non-continuous flight in the smooth run, but chlorpromazine 5 mg/kg induced continuous run with snarling. Methamphethamine 5 mg/kg induced continuous run and autonomic-somatic tonus pattern, and phenobarbital-Na 30 mg/kg depressed the animal to the stage of flight. Diazepam, chlordiazepoxide and phenobarbital-Na inhibited thumping, while chlorpromazine, nitrazepam and methamphethamine increased the incidence of thumping. Chlorpromazine transformed the non-continuous run into autonomic-somatic responses of conditioning. Diazepam transformed the non-continuous run into a continuous one. Phenobarbital-Na transformed the non-continuous run into autonomic-somatic responses. Methamphethamine transformed the non-continuous run into a withdrawal response. It would thus appear that the non-continuous flight, thumping and the non-continuous run conditioning are forms of conflict in behavior which can be applied to study of emotional response with psychotropic drugs.
Assuntos
Condicionamento Psicológico/efeitos dos fármacos , Conflito Psicológico , Emoções/efeitos dos fármacos , Hipotálamo/fisiologia , Psicotrópicos/farmacologia , Animais , Clordiazepóxido/farmacologia , Clorpromazina/farmacologia , Diazepam/farmacologia , Relação Dose-Resposta a Droga , Estimulação Elétrica , Reação de Fuga/efeitos dos fármacos , Hipnóticos e Sedativos , Masculino , Metanfetamina/farmacologia , Camundongos , Nitrazepam/farmacologia , Fenobarbital/farmacologia , CoelhosRESUMO
An attempt was made to induce conflict behavior in rabbits by conditioning under hypothalamic electrical stimulation. Behavioral analysis was performed using our newly devised technique which employs the use of a vibration apparatus fixed to head and waist, and a recording of various behavior. Conditioning was carried out by sensory stimuli flight behavior. Reinforcement was as follows: the CS used was flickering light photic (10 Hz, 10 musec.,) and acoustic (250 Hz, 15 dB) and UCS electrical stimulation (100 Hz, 1 msec., not exceeding 2 v) in the medial hypothalamic area and peri-fornix. The restrained animals were placed on a table in an acoustically isolated room with a discrete monotonous background noise. CRs were obtained within a short time as were responses: (1) During the autonomicsomatic responses, (2) continuous run and (3) non-continuous run. Data obtained during the non-continuous run represent a conflict-induced type of behavior which may be applied in studies related to the psychopharmacological actions of drugs.
Assuntos
Condicionamento Clássico/fisiologia , Medo/fisiologia , Hipotálamo/fisiologia , Animais , Estimulação Elétrica , Habituação Psicofisiológica , Masculino , Métodos , Modelos Psicológicos , Estimulação Física , Coelhos , Reforço Psicológico , RespiraçãoRESUMO
To examine whether a decrease in cytosolic Ca2+ affects fibrillation potentials, we studied effects of dantolene on these potentials in denervated rat muscle. Administered intraperitoneally, dantrolene sodium (12-22 mg/kg) abolished fibrillation potentials and subthreshold oscillating potentials over 2.5-6 h without affecting excitability of the muscle to electrical stimulation. Fibrillation potentials reappeared 36-96 h after administration of dantrolene. We suggest that cytosolic Ca2+ has a specific role in generating fibrillations.
Assuntos
Dantroleno/farmacologia , Denervação Muscular , Relaxantes Musculares Centrais/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/inervação , Animais , Temperatura Corporal/efeitos dos fármacos , Estimulação Elétrica , Eletromiografia , Eletrofisiologia , Masculino , Músculo Esquelético/fisiologia , Ratos , Ratos WistarRESUMO
Myoelectric signals were detected from the tibialis anterior muscle of 5 subjects with a quadrifilar needle electrode while the subjects generated isometric forces that increased linearly with time (10% of maximal voluntary contraction/s) up to maximal voluntary level. Motor unit firing rates were studied as a function of force throughout the full range of muscle force output. The relationship between force and firing rate was found to contain three distinct regions. At recruitment and near maximal force levels, firing rates increased more rapidly with force than in the intermediate region. Furthermore, in the regions with rapid increases, the rate of change of firing rate was correlated to the recruitment threshold, with higher recruitment threshold motor units displaying greater rates of change. In the intermediate region, all motor units had similar rates of change of firing rate. A weak positive correlation was found between initial firing rate and recruitment threshold. Firing rates of motor units at any instant were found to be ordered according to the recruitment order: at any given time in the contraction motor units with lower recruitment thresholds had higher firing rates than units with higher recruitment thresholds. Firing rates of all motor units were observed to converge to the same value at maximal forces. Mechanisms underlying motor unit recruitment and firing rate modulation are discussed in the context of a conceptual model.
Assuntos
Neurônios Motores/fisiologia , Potenciais de Ação , Adulto , Limiar Diferencial , Humanos , Perna (Membro) , Contração Muscular/fisiologia , Músculos/inervação , Recrutamento NeurofisiológicoRESUMO
Despite advances in the study of exercise for acute myocardial infarction (AMI) patients, few studies on exercise for post-AMI heart rupture patients have been reported. We assessed three cases of heart rupture (of the left ventricular free wall in two cases and of the ventricular septum in one case) in post-AMI patients who underwent three-graded exercise. Two of the three patients were operated on, whereas one patient was managed conservatively for heart rupture. Two of the three cases had also suffered cerebral infarction post-AMI. The exercise program was composed of three grades, slow level walking (grade 1), mild reconditioning and activities of daily living (ADL) exercises (grade 2), and optional endurance training using machines below 75% of predicted maximal heart rate (grade 3). Electrocardiograms and blood pressure were monitored during all exercises. All patients had muscle weakness, poor endurance capacity, as well as low cardiac function (28-47% of left ventricular ejection fraction). Two patients underwent grades 1 and 2 exercise programs, and the other performed grades 1, 2, and 3 exercise programs over a 3- to 10-wk period. We observed improvement in the double product, work capacity, and ADL without congestive heart failure, ischemic attack, or serious arrhythmias. However, the youngest patient, who underwent the grade 3 exercise program, died from a cardiac event 10 mo after onset of AMI. We conclude that post-AMI heart rupture patients should undergo delayed, gradual, low-level graded exercise (4-6 metabolic equivalents), with monitoring of blood pressure and electrocardiograms to improve work capacity, ADL, and the quality of life. However, daily activity and exercise intensity should be promptly supervised for those with severely deteriorated cardiac functions to prevent sudden cardiac event.
Assuntos
Terapia por Exercício , Ruptura Cardíaca Pós-Infarto/reabilitação , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Eletrocardiografia , Teste de Esforço , Terapia por Exercício/métodos , Feminino , Ruptura Cardíaca Pós-Infarto/etiologia , Ruptura Cardíaca Pós-Infarto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Resistência Física/fisiologia , Avaliação da Capacidade de TrabalhoRESUMO
MCI-2016 showed little influence on coagulation (APTT) and fibrinolysis (plasma clot lysis activated by urokinase) at doses (concentrations) as high as 300 mg/kg, p.o. or 8.6 X 10(-4) M. Hemolytic action of MCI-2016 was only observed at the concentrations above 2 mM. The drug also showed no influence on blood glucose level (30-300 mg/kg, p.o.). Effects of MCI-2016 on hemorheological properties were studied either in vitro or ex vivo. Above the doses (concentrations) of 100 mg/kg, p.o. and 10 microM, MCI-2016 suppressed the mechanical hemolysis and accelerated the membrane filtration rate. These effects of MCI-2016 were superior to those of cinepazide, Ca-hopantenate, meclofenoxate and pentoxyfylline. MCI-2016 also inhibited platelet aggregation induced by collagen with the IC 50 of 35 to 60 microM (rabbit and human platelets). Secondary aggregations of ADP and epinephrine were also inhibited by MCI-2016. As for reference drugs, bencyclane showed inhibitory patterns similar to MCI-2016. Other drugs examined exhibited little effect. In summary, it may be suggested that MCI-2016 exhibits beneficial influences in the clinical fields of cerebrovascular diseases.