Orientador: Lourenço Bozzo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piraciacaba / Made available in DSpace on 2018-07-21T20:13:07Z (GMT). No. of bitstreams: 1 Bozzo_RicardodeOliveira_M.pdf: 5946295 bytes, checksum: a06ba57aa14f5358b8cdc21ddea8845d (MD5) Previous issue date: 1996 / Resumo: A ação de uma droga antiinflamatória não-esteróide (diclofenaco sódico) foi avaliada, em diferentes perfodos de tempo, após uma incido cirúrgica na pele de ratos machos, adultos jovens, pesando mais ou menos 250 gramas cada. Os grupos experimentais receberam, 1 hora antes da incido cirúrgica, uma injeção intraperitoneal de diclofenaco sódico (Voltaren). Um grupo recebeu 2 mg/Kg de peso da droga (G2); o outro recebeu 4 mgJKg de peso da droga (G4). O grupo controle (GC) .recebeu 2 mgJKg de peso de PBS, também por injeção intraperitoneal. Uma hora após estas administrações, foi feita uma incido cirúrgica de aproximadamente 1 cm de extensao, na pele do dorso dos 72 ratos. Cada grupo de 6 ratos (2 do GC, 2 do G2 e 2 do G4) era sacrificado após um determinado perfodo de tempo ,3,6,12,24,48,72,96,120 e 168 horas após a incid,o). Os efeitos da droga na evolução do processo innamatório e da reparação foram avaliados através dos aspectos morfológicos (macro e microcóspicos). As observações macroscópicas e a nfvel de microscopia óptica mostraram que o diclofenaco sódico modifica as respostas teciduais, provocando um re tardo na evolução do processo innamatório e na cura da ledo. Estas alterações são mais evidentes a partir das 72 horas, e de maneira mais marcante no grupo G4 que nos demais. o bloqueio da biossfntese de prostaglandinas pelo diclofenaco sódico modificou a expressão macro e microscópica da ledo nos diferentes perfodos de tempo, possivelmente pela intensificaç:lo na formaç:lo de leucotrienos. Apesar da ação antiinftamat6ria do Voltaren, outros mediadores qufmicos da inftamação além das prostaglandinas, mantiveram a evolução do processo. As possfveis interações das diferentes substancias liberadas na área lesada, do momento zero até 168 horas, determinaram as alterações observadas nesta pesquisa / Abstract: Not informed. / Mestrado / Farmacologia / Mestre em Ciências

Orientador: Eduardo Dias de Andrade / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-22T04:49:23Z (GMT). No. of bitstreams: 1 Arruda_AnaMariaSoaresde_D.pdf: 3153753 bytes, checksum: 979fe0671f2a6ad1366613fe933fb33c (MD5) Previous issue date: 1996 / Resumo: o deflazacort é um antiinflamatório esteróide, que tem sido empregado em clínica médica, com a vantagem de apresentar uma menor incidência de alguns dos efeitos colaterais associados aos glicocorticóides (hiperglicemia, osteoporose). Não há dados, na literatura, a respeito de seu efeito antinociceptivo em modelos experimentais. Em vista disto, propusemo-nos estabelecer, em animais de laboratório, alguns parâmetros para a avaliação do seu efeito antinociceptivo. O deflazacort (0,075 a 2,4mg/kg, ip), foi administrado 60 minutos antes do estímulo nocivo, e seus efeitos comparados com um controle (solução salina 0,9%) ou com doses crescentes de dexametasona (1,0 a 4,Omg/kg, ip) ou indometacina 2,Omg/kg, se. Foram empregados dois modelos para se avaliar a dor (teste de contorções abdominais induzi das pelo ácido acético e teste da formalina), em camundongos, e outro método experimental para a avaliação da migração de leucócitos PMN à cavidade peritoneal, nesta mesma espécie animal. Resultados: o deflazacort diminuiu o número de contorções a partir da dose de O, 15mg/kg, enquanto que a dexametasona apresentou este efeito a partir da dose 2,Omg/kg, ambos de modo dose dependente (salina: 32,1 :t 0,96 contorções; deflazacort 0,15mg/kg: 18,8 :t 3,39 contorções; indometacina 2,Omg/kg: 13,3 :t 3,32 contorções, p<0,05). No teste da formalina, o deflazacort diminuiu o tempo total da segunda fase a partir fia dose 1,2 mg/kg, enquanto que a dexametasona foi eficaz a partir da dose de 2,Omg/kg, ambos não apresentando efeito dose dependente (salina: 246,5 :t 18,90 s; deflazacort 1,2mg/kg: 120,1 :t 21,95 s; dex}l.ffietasona 2,Omg/kg: 134,9 :t 39,38 s; indometacina 2,Omg/kg: 153,0 :t 19,21 s, p<0,05). Na migração leucocitária, p deflazacort inibiu a migração de PMN a partir da dose de 0,3mg/kg, enquanto que a dexametasona apresentou o mesmo efeito em dose igual ou superior a 3,Omg/kg (salina: 0,59 :t 0,06 xl06 PMN/rnL; deflazacort 0,3mg/kg: 0,31 :t 0,04 xl06 PMN/rnL; dexametasona 3,Omg/kg: 0,21 :t 0,04 xl06 PMN/rnL, p<0,05). Estes resultados apontam para um potente efeito antinociceptivo do deflazacort nos modelos testados, além de uma significante inibição da migração de leucócitos PMN / Abstract: The aim of this work is to stablish parameters for experimental assay to deflazacort, a glucocorticoid wich have few side effects on bone and glycemia. Two nociceptives and one of PMN accmnulation experimental models were done in order to evaluate the antinociceptive and antiinflammatory effects of deflazacort, when compared with dexamethasone and indometacin. SWISS male mice were treated with crescent doses of deflazacort (Calcort@, 0.075mg!kg to 2.4mg!kg), or dexamethasone (Decadron@, 1.0 to 4.0mg!kg), or saline 0.9% or indometacin 2.0mg!kg, 60 minutes before the nocive challenge. Acetic ~id writhing test showed that slow doses of deflazacort inhibit the acetic acidinduced stretching and writhing movements. lu fact, deflazacort were more potent that dexamethasone in this test (saline: 32.1 :t 0.96 movements in 15 ,minutes; deflazacort O, 15mg!kg: 18.8 :t 2.86 moviments; dexamethasone 2.0mg!kg: 22.2 :t 3.53 movements; indometacin 2.0mg!kg: 1~3.3 :t 3.32 movements, p<0.05). Deflazacort also were more potent in inhibit the late phase ofFormalin test (saline: 246.5 :!: 18.90 s; deflazacort 1.2mg!kg: 120.1 :!: 21.95 s; dexamethasone 2.0mg!kg: 134.9 :!: 39.38 s; indometacÍn 2.0mg!kg: 153.0 :!: 19.21 s, p<0.05). lu the model of leukocyte PMN migration, treatment with deflazacort, doses equal to or higher than 0.3mg!kg inhibited the PMN accumulation, while dexamethasone showed the same effect with doses equal to or higher than 3.0mg!kg (saline: 0.59 :t 0.06 xl06 PMN/mL; detlazacort O.3mg!kg: 0.31 :t 0.04 xl06 PMN/mL; dexamethasone 3.0mg!kg: 0.21 :!: 0.04 xl06 PMN/mL, p<0.05). These results point to a potent antinociceptive effect of detlazacort, when compared to dexamethasone, in the tested experimental models / Doutorado / Farmacologia / Doutor em Ciências

Orientador: Ennes Macari de Abreu / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-22T21:28:17Z (GMT). No. of bitstreams: 1 Farhat_MarilzaAparecidaStolf_D.pdf: 2646337 bytes, checksum: 13bae65fe572215e762981ab9811ed9b (MD5) Previous issue date: 1996 / Resumo: o presente experimento clínico teve como objetivo avaliar, comparativamente a eficácia de nimesulide e de piroxicam, no controle da dor, do trismo e do edema, após extração de terceiros molares inferiores retidos. Foram utilizados 18 pacientes saudáveis, com necessidade da remoção dos 2 terceiros molares inferiores retidos, sendo esta retenção, semelhante. Cada indivíduo foi o controle de si mesmo, recebendo 4 comprimidos de 100 mg de nimesulide, sendo 1, administrado 1 h antes da remoção do dente e os demais a cada 12 h, ou 2 comprimidos de 20 mg de piroxicam, sendo 1 administrado antes da cirurgia e o outro no dia seguinte. Todos os pacientes receberam 1 comprimido de 5,0 mg de diazepam 1 h antes da cirurgia: e 10 comprimidos de 500 mg de paracetamol a serem consumidos em casa, em caso de dor, anotando o tempo e o número de comprimidos utilizados. Os resultados obtidos demonstraram que ambas as drogas tiveram comportamento semelhante quanto ao trismo e ao edema, não havendo diferenças estatísticas entre elas, embora na análise do edema o piroxicam tenha demostrado maior eficácia do que o nimesulide no período de O - 24 h e menor no de 24 - 48 h. O nimesulide demonstrou maior eficácia do que o piroxicam no controle da dor nos períodos de O-24, 24 - 48 e 48 -72 h. A partir destes resultados, foi possível concluir que o uso do nimesulide, no pós-operatório de extrações de terceiros molares retidos, seria o mais indicado, com a menor probabilidade de aparecimento de efeitos indesejáveis / Abstract: The purpose of this study was to evaluate the efficacy of nimesulide (100 mg) and piroxicam (20 mg) in the control of pain, trismus, and swelling, after extraction of impacted lower third molars. The population comprised 18 healthy subjects who needed removal of 2 identical mandibular third molars. Each individual served as his own control as the teeth were removed in 2 sittings with either nimesulide 100 mg - 4 tablets) - one tablet 1 h before the removal of the tooth and each 12 h, or piroxicam (20 mg - 2 tablets) - one tablet 1 h before the extraction and the their in the following day. All the patients recei ved 1 h before the surgery one tabler of 5,0 mg diazepam. After the operations the patients were supplied with 10 tables of 500 mg paracetamol and asked to record the time and number of tablets intake. The results showed that both drugs had a similar effect in the swelling and trismus with no statistical difference, although in the swelling evaluation the piroxicam showed greater efficacy than the other drug in the period of O - 24 hs and less in the period of 24 - 48 hs. Nimesulide had a greater efficacy than piroxican in the control of pain in the periods of o - 24, 24 - 48 and 48 - 72 hs. It was concluded that the use of nimesulide would be more indicated than piroxicam with a minor probability of side effects / Doutorado / Farmacologia / Doutor em Ciências

Orientador : Sergio de Toledo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-03T10:11:13Z (GMT). No. of bitstreams: 1 Gurgel_BrunoCesardeVasconcelos_M.pdf: 5306561 bytes, checksum: 7b6dbd830d2cb4851e38bd0110a06fba (MD5) Previous issue date: 2003 / Resumo: o objetivo do presente estudo foi avaliar, histometricamente, a influência de uma droga antiinflamatória não esteroidal seletiva para a cicloxigenase-2, meloxicam, sobre a perda óssea inter-radicular bem como o seu efeito residual após a suspensão da administração. O experimento foi realizado em 75 ratos machos adultos Wistar com doença periodontal induzida por ligadura, divididos aleatoriamente em 5 grupos com 15 animais cada, recebendo diariamente, via subcutânea, os seguintes tratamentos: ratos nos grupos 1A e 1 B receberam o volume de 1mllkg de NaCI 0,9%, por 15 dias e 45 dias respectivamente, servindo como controle; os animais do grupo 2A e 2B receberam 3mg/kg do meloxicam, nos mesmos períodos experimentais e os do grupo 3 receberam 3mg/kg do meloxicam, cuja administração foi suspensa aos 15 dias e NaCI 0,9% administrado por mais 30 dias. A avaliação histométrica mostrou que houve uma diminuição estatisticamente significativa da reabsorção óssea interradicular para os grupos tratados com o meloxicam, tanto aos 15 dias quanto aos 45 dias após a administração da droga (P<0,05). Não se observou qualquer efeito remanescente da droga sobre a perda óssea após a suspensão da sua administração (P>0,05). Os resultados indicaram que o inibidor seletivo de COX-2 foi eficiente na diminuição da reabsorção óssea apenas durante a sua administração. A modulação da resposta do hospedeiro promovida pelo meloxicam associada a periodontite induzida pode ser considerada um possível adjunto à terapia da doença periodontal inflamatória quando utilizado de forma contínua / Abstract: The objective of this study was to evaluate, histometrically, the influence of a nonsteroidal anti-inflammatory drug, selective cyclooxygenase-2 inhibitor, on inter-radicular bone loss as well as the post-treatment etfect after administration withdrawal. This experiment was performed in 75 male, adults Wistar rats with ligature-induced periodontal disease, randomly divided in 5 groups with 15 animais each, receiving daily injections, subcutaneous, the following treatments: rats from groups 1A and 1 B received 1 ml/kg of saline solution for 15 and 45 days respectively, performing as control group; animais from group 2A and 2B received 3mg/kg of meloxicam, in the same periods and animais from group 3 also received 3mg/kg of meloxicam, whose drug administration was withdrawn on 15 days and saline solution administered for more 30 days. The histometric evaluations showed that there was a statically significant bone loss reduction for treated groups in both 15 and 45 days (P<0,05). It was not observed any statically significant remaining etfect on bone loss after drug withdrawal (P>0,05). The results indicated that the selective COX-2 inhibitor was efficient on bone loss reduction only during the continued administration. The host response modulation promoted by meloxicam associated with ligature-induced periodontitis may be considered as a possible adjunct to therapy of inflammatory periodontal disease / Mestrado / Periodontia / Mestre em Clínica Odontológica

M.Ing. (Civil Engineering) / Please refer to full text to view abstract

A dissertation submitted in partial compliance with the requirements for the Master's Degree in technology: Chiropractic, Technikon Natal, 2001. / The purpose of this study was to evaluate the relative effectiveness of manipulation versus meloxicam (a Non-Steroidal Anti-Inflammatory Drug) to determine which is more beneficial in treating osteoarthritis of the knee. This was a prospective, randomized clinical trial consisting of a population of sixty voluntary subjects, diagnosed as suffering from osteoarthritis of the knee. The patients were divided equally into two groups of thirty, with Group A receiving chiropractic manipulative therapy on eight consultations over three weeks, and Group B receiving meloxicam 7,5mg tablets once daily for three weeks. Capturing of the subjective and objective data for both groups took place on the first, fourth and eighth consultations. Subjective data was captured using the Numerical Pain Rating scale-l 01, the Visual Analogue scale, as well as the Patient -Specific functional scale. Objective data was gathered from goniometric and pressure algometer measurements. / M

Gold compounds have been used for the treatment of rheumatoid arthritis since the mid 20th century as a disease modifying anti-rheumatic drug. Auranofin, an oral anti-rheumatic drug, has been used for many years in the treatment of rheumatoid arthritis (RA). Although the drug has been successful in treating the symptoms of RA, many patients discontinue its use due to severe toxicity over long periods of continued treatment. Since the introduction of auranofin in 1985 there has been no new clinically approved gold drug. Drug discovery research is directing focus on overcoming these toxicity problems. Much of the problems related to the toxicity related to auranofin are due to its lipophilicity. As a result, three compounds (Asa-fin, Mpta-fin and Pta-fin) with varying substituents were synthesised and hence the lipophilic- hydrophilic balance was modulated. All compounds including auranofin were tested against normal cells to determine its toxicity as well as its anti-inflammatory activity. Three novel auranofin derivatives were compared to auranofin with regards to lipophilicity, toxicity and anti-inflammatory properties The lipophilicity of the three compounds were compared to auranofin using the octanol-water partition coefficient method. All the novel compounds showed variable lipophilicity compared to auranofin, with Pta-fin and Mpta-fin being more hydrophilic than auranofin. The cytotoxicity of these novel gold compounds Asa-fin, Mpta-fin and Pta-fin were compared to auranofin using primary porcine hepatocytes and chicken embryo fibroblasts cultures. A metabolic assay based on the reactivity of 3-[4,5-dimethylyhiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) with viable cells was done to measure the effect of the drugs on the growth of cultures. All three novel compounds proved less toxicity at comparable concentrations in primary porcine hepatocytes and in fibroblast proliferation, Asa-fin and Mpta-fin proved less toxic than Auranofin. The Anti-inflammatory activity of the experimental compounds was determined by testing the effects of the experimental compounds on human lymphocyte proliferation. The MTT assay was used to measure the effect of the drugs on the growth of the cell cultures. All three compounds inhibited the proliferation of human lymphocytes with Pta-fin having the least effect. The effect of these drugs was also evaluated on the reactive oxidant production by chemiluminescence and flow cytometry on resting, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) and Phorbol Myristate Acetate (PMA) stimulated human neutrophils. Oxidant production by neutrophils was measured after a 45-minute incubation period with luminol enhanced chemiluminescence. Treatment of neutrophils with auranofin and the three compounds showed that auranofin, Asa-fin and Mpta-fin had a biphasic activity on hydrogen peroxide production with higher concentrations decreasing hydrogen peroxide production, possibly leading to the anti-inflammatory action of these drugs. With Pta-fin no decrease in hydrogen peroxide was observed. Using flow cytometry three dyes specific to different reactive oxygen species were used. 2’, 7’-Dichloroflourescein diacetate (DCFH) is specific for detecting nitric oxide, Dihydrorhodamine 123 (DHR) is specific for detecting hydrogen peroxide and Hydroethidine (HE) is specific for detecting superoxide. Oxidant production was measured after a 30 minute incubation period with the relative dyes on a flow cytometer. Auranofin and Asa-fin decreased hydrogen peroxide and superoxide production. None of the drugs had an effect on nitric oxide production. The expression of the â2-integrin adhesion molecule, CR3, on resting and PMA stimulated neutrophils treated with the experimental compounds was measured by flow cytometry. CR3 expression by neutrophils was measured after 10 minute incubation in the dark with CD11b FITC monoclonal antibody. Treatment of neutrophils with auranofin and the three experimental compounds showed a decrease in CR3 expression on resting and stimulated neutrophils, however the effect was more marked in stimulated neutrophils. The Anti-inflammatory activity of the experimental compounds was determined by testing the effects of the experimental compounds on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX 2) in resting and lipopolysaccharide (LPS) stimulated human monocytes. COX 1 and 2 production was measured by flow cytometry. Treatment of monocytes with the experimental compounds showed a decrease in COX 2 production in stimulated monocytes but an increase in COX 2 production in resting monocytes. No effect on COX 1 production was observed with the experimental compounds. Prostaglandin E2 (PGE2) was measured with a Prostaglandin E2 Enzymeimmunoassay (ELISA) kit on human macrophages. Auranofin, Asa-fin, Mpta-fin and Pta-fin inhibited the production of PGE2. Auranofin and Asa-fin inhibited the PGE2 directly proportional to the drug concentration. The effect of these drugs was also evaluated on various inflammatory cytokines using an inflammatory cytokine kit and measured on a flow cytometer. The cytometric bead array (CBA) human inflammation kit was used to quantitatively measure interlukin-8(IL-8), interlukin-1â (IL-1â), interlukin-6 (IL-6), interlukin-10 (IL-10), tumour necrosis factor alpha (TNFá) and interlukin-12p70 (IL-12p70). Auranofin and Asa-fin decreased IL 10, TNFá, and IL1â in stimulated cells. No effect was observed on IL 8, IL-12p70 and IL 6. With Mpta-fin and Pta-fin, no significant effect was observed in the cytokines tested. Drug toxicity was evaluated in mice using all four compounds in BALB/c inbred mice. Aspartate transaminase (AST), gamma glutamine transferase (GGT), urea and creatine levels were measured in the test mice. The group receiving the highest dose of Asa-fin showed the greatest elevation of AST . The lowest dose of the auranofin treatment group showed the greatest elevation in GGT, however this increase was not seen in the subsequent higher dosing groups. None of the treatment groups indicated an increase in urea levels. Mpta-fin and Pta-fin showed no increase in the liver enzymes or in urea and creatine. The results of this work are indicative that novel gold compounds could play a promising role in anti arthritic applications. Asa-fin exhibited similar anti-inflammatory activity to auranofin but in vivo toxicity was high. Mpta-fin showed slightly inferior anti-inflammatory activity to auranofin but in vivo toxicity profiles were much more promising. Pta-fin showed the least anti-inflammatory activity of the three novel compounds tested with a similar in vivo toxicity profile as Mpta-fin. / Dissertation (MSc)--University of Pretoria, 2009. / Pharmacology / unrestricted

No abstract / Applied Science, Faculty of / Chemical and Biological Engineering, Department of / Graduate

Crevice corrosion experiments have been conducted on Inconel 600 and Inconel 625 exposed to two principle test solutions of 1 M NaCl and 1 M NaCl + 0.01 M Na₂S₂0₃ (Sodium Thiosulphate) at three temperatures, 22°C, 55 °C and 80°C. The crevice corrosion tests were performed in a corrosion cell which was constructed from PTFE (Polytetrafluoroethylene, Teflon) and Pyrex glass. Features of the cell included the utilization of an artificial Teflon-metal crevice and provisions to monitor crevice corrosion current, active crevice corrosion potential and active crevice pH. Additional experiments included potentiodynamic anodic polarization tests on pure Ni, Alloy 600, and Alloy 625 in bulk solution environments and in simulated crevice solutions. Crevice corrosion morphology and compositional analysis of the corrosion products was studied using a scanning electron microscope equipped with an X-ray energy dispersive spectroscopy (EDS) system. Results show that crevice corrosion rates increase with increasing temperature for Alloy 600 in both principle test solutions. X-ray EDS analysis indicated that an insoluble nickel sulphide corrosion product formed on Alloy 600 in a solution of 1 M NaCl + 0.01 M Na₂S₂0₃. For the Alloy 600, in a solution of 1 M NaCl + 0.01 M Na₂S₂0₃, initiation times were significantly reduced and crevice corrosion propagation rates enhanced, as compared to Alloy 600 in 1 M NaCl. The decrease in initiation times has been attributed to the destabilizing nature of the S₂O₃⁻² species on the passive oxide film. Enhanced propagation rates have been attributed to the presence of H₂S in the crevice solution and the formation of an adsorbed species Ni(H₂S)ads which enhances the anodic dissolution reaction. The H₂S in the active crevice solution originated from the thermodynamically favoured electrochemical reduction of the S₂0₃⁻² species in the active crevice solution. Experiments on Alloy 625, which is alloyed with molybdenum, (Mo), show that it was virtually immune to crevice corrosion as compared to Alloy 600 which is not alloyed with Mo. The resistance of Alloy 625 to crevice corrosion initiation has been attributed to the stabilizing nature of MoO₂ in the passive oxide film. For an actively corroding system, the formation of the molybdate species MoO₄⁻² may act as an anodic inhibitor and effectively enhance the repassivation of the passive film. / Applied Science, Faculty of / Mining Engineering, Keevil Institute of / Graduate

Quinacainol, 1-[2-(1,1-dimethylethyl)-4-quinolyl]-3-(4-piperidyl)-1-propanol is a class I antiarrhythmic agent provisionally subclassified as Ic. Studies were carried out in order to (1) determine the actions of quinacainol in acute myocardial ischæmia, (2) ascertain the mechanism(s) responsible for these actions, and (3) ascertain the appropriateness of its subclassification. Toxicological, hæmodynamic, and ECG effects in chronically prepared conscious rats were determined following administration of 1, 2, 4, or 8 mg/kg of quinacainol given i.v. over 10 minutes on alternate days. Toxicity referable to the heart was seen at doses of 8 mg/kg and above. In rats given 8 or 16 mgkg, arrhythmias occurred. Quinacainol had no major effects on blood pressure, unlike most class I antiarrhythmics, but lowered heart rate (not statistically significantly) and prolonged P-R interval and QRS duration. In an attempt to protect against ischæmic arrhythmias, doses of 2 mg/kg and 4 mg/kg were given. The high dose gave the best protection. It reduced the incidence of ventricular tachycardia (VT) from a control value of 80% to 30%, and reduced the incidence of ventricular fibrillation (VF) from a control value of 60% to 10%. An increase in the incidence of premature ventricular contractions was seen at both doses. Blood pressure was not adversely effected although slight bradycardic effects as well as prolongation of the P-R interval were seen at both doses. Both doses reduced S-T segment and delayed onset of elevation of S-T segment and R-wave which were induced by coronary occlusion. Sensitivity to electrical stimulation was tested in pentobarbital anæsthetised rats using ventricular electrodes. Doses of 0.5, 1, 2, and 4 mg/kg were given cumulatively as a 10 min infusion every 25 min. Quinacainol did not affect QRS duration or the Q-Tc interval but dose-dependently widened P-R interval when compared to pretreatment. Quinacainol dose-dependently increased threshold current, threshold duration, and ventricular fibrillation threshold. In addition, quinacainol elevated effective refractory period while decreasing maximum following frequency. Open-chest rats under pentobarbital anæsthesia were used to record the effects of quinacainol on epicardial intracellular potentials. Recordings were made by conventional microelectrode techniques before and after cumulative doses of 0.5, 1, 2, 4, and 8 mg/kg i.v. Quinacainol dose-dependently reduced phase zero of the action potential (AP) and AP height but did not influence other phases of the AP (with the exception of prolonging repolarization at the highest dose); actions indicative of class Ic. Effects of quinacainol on isolated rat hearts were assessed using a modified Langendorff heart preparation and were compared with those of tetrodotoxin (TTX). Quinacainol widened the P-R interval and QRS duration without having major effect on the Q-Tc interval. In addition it slowed the sinus beating rate. Quinacainol was more potent than TTX. All findings indicated that quinacainol is a potent antiarrhythmic agent with Na⁺channel blocking properties. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate