Thesis (Ph. D.)--University of Chicago, 1939. / Lithoprinted. "List of references": p. 17-19.

O objetivo deste estudo foi avaliar os efeitos cardiovasculares da infiltração maxilar usando lidocaína 2% associada à epinefrina 1:100.000, articaína 4% associada à epinefrina 1:100.000 e 1:200.000 em diferentes etapas da consulta odontológica para realização de procedimento restaurador. Vinte voluntários receberam, aleatoriamente, 1,8 ml dos três anestésicos locais. A pressão arterial sistólica, diastólica e média e a freqüência cardíaca foram avaliadas pelos métodos oscilométrico e fotopletismográfico em sete etapas da consulta odontológica. A análise estatística dos parâmetros cardiovasculares através dos testes ANOVA e Tukey não mostrou diferenças significativas entre as três soluções anestésicas. Houve diferença estatisticamente significante para os parâmetros cardiovasculares entre as diferentes etapas clínicas da consulta odontológica. A variação dos parâmetros cardiovasculares é semelhante para as soluções de articaína e lidocaína associadas à epinefrina e é influenciada pelas etapas da consulta odontológica. / The aim of this study was to evaluate cardiovascular effects by maxillary infiltration using 2% lidocaine with 1:100.000 epinephrine, 4% articaine with 1:100.000 and 1:200.000 epinephrine in different stages of dental appointment for restorative procedures. Twenty healthy patients randomly received 1,8 ml of the three local anesthetics. Systolic blood pressure, average blood pressure, diastolic blood pressure and heart rate were evaluated by the oscillometric and photoplethysmograph methods in seven stages of the appointment. Statistical analysis by ANOVA and Tukey tests of cardiovascular parameters did not show significant differences between the anesthetic associations. There were significant differences for the parameters among different clinical stages of the dental appointment. The variation of cardiovascular parameters is similar for articaine and lidocaine solutions and it is influenced by the stages of the dental appointment.

O objetivo dessa pesquisa foi avaliar o tempo de latência e duração pulpar anestésica da dose de 1,8ml das seguintes soluções anestésicas locais: cloridrato de articaína 4% associado à epinefrina 1:100.000 (ART 100) e 1:200.000 (ART 200) e cloridrato de lidocaína 2% associado à epinefrina 1:100.000 (LIDO 100) no bloqueio convencional do nervo alveolar inferior. A amostra do experimento consistiu de vinte pacientes normorreativos, submetidos a três consultas para tratamento restaurador de baixa complexidade em três dentes posteriores inferiores. Os períodos de latência e duração da anestesia local na polpa dentária foram monitorados com um estimulador pulpar elétrico (Vitality Scanner Model 2006®-SybronEndo, CA, EUA). Para análise e comparação dos resultados da latência e duração pulpar das três soluções anestésicas locais foi utilizado o teste paramétrico ANOVA e o teste auxiliar de Bonferroni com nível de significância fixado em 5% (p<0,05). Em relação ao período de latência pulpar não houve diferença estatisticamente significante entre nenhuma das três soluções anestésicas locais utilizadas (p > 0,05). Já em relação ao período de duração pulpar houve diferença estatisticamente significante entre ART 100 e LIDO 100 (p=0,000) e entre ART 200 e LIDO 100 (p=0,000). Portanto, a latência das duas soluções de articaína foram similares à solução de lidocaína, mas ambas apresentaram duração de ação anestésica maior do que a solução de lidocaína. / The aim of this study was to evaluate the time of onset and duration of pulp anesthetic dose of 1.8 ml of local anesthetic solutions following: 4% hydrochloride articaine associated with epinephrine 1:100.000 (ART 100) and 1:200.000 (ART 200) and 2% hydrochloride of lidocaine associated with epinephrine 1:100.000 (LIDO 100) in alveolar nerve block lower. The sample of the experiment consisted of twenty healthy patients, underwent three appointments for restorative treatment of low complexity in three subsequent lower teeth. The periods of onset and duration of local anesthetic in dental pulp were monitored with an electric stimulator pulp (Vitality Scanner®, Model 2006 - SybronEndo, CA, USA). To analyze and compare the results of onset and duration of the three pulp solutions local anesthetic was used parametric ANOVA test and the test of Bonferroni help with significance level set at 5% (p < 0.05). For the period of onset there was no statistically significant difference between any of the three approaches used local anesthetic (p> 0.05). Already in relation to the duration of pulp statistically significant difference between ART 100 and LIDO 100 (p = 0000) and between ART 200 and LIDO 100 (p = 0000). Therefore, the onset of the two solutions of articaine were similar to the solution of lidocaine, but both showed duration of anesthetic action superior to the solution of lidocaine.

O presente trabalho teve como objetivo avaliar e comparar a reatividade vascular de agentes vasoconstritores presentes nas soluções anestésicas locais (Adrenalina - vasoconstrição e vasodilatação; Felipressina - vasoconstrição), nas doses de 80, 160, 320, 640 e 1280ng (adrenalina) ou 0,25; 0,5; 1; 2 e 4 x10-3UI (felipressina), em leito arterial mesentérico deratos normotensos, diabéticos, hipertensos renais um-rim, um-clip (1R-1C) e hipertensos1R-1C-diabéticos. E correlacionar tal reatividadecom expressão de RNAm dos receptores 1A e 2- adrenérgicos, V1A para vasopressina e AT1A, AT1Be AT2 para angiotensina II visando verificar se a hipertensão arterial e o diabetes mellitus provocam alteração em modelo indutivo e isogênico. Ratos Wistar pesando 110-160g, foram anestesiados com mistura de quetamina e xilazina (50+10mg/ml/kg de peso), tiveram seu abdômen aberto e receberam um clip de prata com abertura 0,25mm na artéria renal esquerda, removendo-se cirurgicamente o rim direito (ratos 1R-1C). Após 14 dias, receberam injeção subcutânea de estreptozotocina (50 e 60mg/kg de peso) para indução do diabetes mellitus sendo a glicemia testada pela veia caudal previamente aos experimentos (diabéticos). Após 30-42 dias da implantação do clip, todos os grupos foram novamente anestesiados e implantou-se cânula de polietileno (PE-50) na artéria carótida esquerda para registro direto da pressão arterial. Após registro da pressão os animais tiveram a artéria principal mesentérica exposta e canulada. O leito arterial mesentérico foi então isolado e colocado em banho com solução nutritiva de Krebs a 37ºC. O cateter foi conectado ao sistema de registro computadorizado (PowerLab®) utilizando software específico (Chart 5Pro ®). Analisaram-se: a pressão máxima (vasoconstrição) e mínima (vasodilatação), o tempo necessário para atingir esse valor, duração total da resposta, integral e integral sobre a linha de base. Os dados foram submetidos à análise de variância de medidas repetidas (ANOVA), seguida do teste de Holm-Sidak (distribuição normal) ou de Mann-Whitney (nãoparamétrico), quando apropriado, nível de significância de 5%. Todas as respostas máximas de vasoconstrição apresentaram comportamento dose-dependente, contudo, para os quatro grupos estudados, a resposta vasoconstritora para adrenalina foi significativamente superior à felipressina (p<0,05). Diabetes e hipertensão reduziram a resposta vasoconstritora da adrenalina e da felipressina, valores de integral sobre a linha de base, respectivamente para grupo controle, diabético, hipertenso e hipertenso-diabético: 2462±465; 1511±236; 2542± 5456 e 3749±819mmHg.s (p<0,05) para adrenalina e 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0,05) para felipressina. Tanto o diabetes quanto a hipertensão, associadas ou não, aumentaram significativamente o tempo para atingir a pressão máxima de vasoconstrição e a duração (p<0,05). As artérias mesentéricas de ratos diabéticos, hipertensos e diabéticos-hipertensos apresentaram expressão significativamente aumentada dos receptores 1Aadrenérgico, AT1B e AT2 para angiotensina II (p<0,05), enquanto receptor AT1A estava com a expressão aumentada apenas nos grupos diabéticos. A expressão do receptor 1A-adrenérgico é discrepante com os achados funcionais, o que pode ser justificado pela fase crônica da doença em que a PCR foi realizada. É possível correlacionar os dados obtidos com a menor atividade vasoconstritora da felipressina observada clinicamente. A maior sensibilidade às moléculas vasoconstritoras pode explicar a maior tendência de pacientes diabéticos desenvolverem hipertensão. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em pacientes hipertensos e diabéticos, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações. / The main goal of this study wasto evaluate and compare vasoconstrictor agents present in local anesthetic solutions (Epinephrine - vasoconstriction and vasodilation, Felypressin - vasoconstriction) vascular reactivity on mesenteric artery bed of normotensive, diabetic, renal hypertensive one-kidney-one-clip (1K1C) and hypertensive 1K1C diabetic rats. Dosagesstudied were 80, 160, 320, 640 and 1280ng (epinephrine) or 0,25; 0,5;1; 2 and 4 x 10-3UI (felypressin). Also, we aimed to correlate artery response with RNAm expression of 1A and 2-adrenoceptors, V1A vasopressin receptor and AT1A, AT1B e AT2 angiotensin receptors, in order to verify if arterial hypertension and diabetes can lead to alterations on a inductive and isogenic model. Wistar male rats weighing 110-160g were anaesthetized with a mixture of ketamine and xylazine (50+10mg/ml/kg), had their abdominal cavity opened and a silver clipwith 0.25-mm gap was implanted in the main left kidney artery, the right kidney was surgically removed (1K1C-rats). After 14 days, they received a subcutaneous injection of streptozotocin (50 and 60 mg/ml/kg) for inducing diabetes, whereas the glycemia was tested via the tail vein prior to surgery (diabetic rats). Around 30-42 after the clip was implanted, all the groups were anaesthetized again and a polyethylene (PE-50) cannula was implanted on the left carotid artery for direct arterial pressure register. After registering the pressure, the animals had their main mesenteric artery exposed and cannulated. The mesenteric artery bed was then isolated and transferred to a bath with Krebs nutritive solution at 37ºC. The catheter was connected to the computer register system (PowerLab®) using a specific software (Chart 5Pro ®). The following parameters were analyzed: maximum (vasoconstriction) and minimal pressure (vasodilating), the amount of time necessary to achieve this number, total duration of the reaction, integral and integral over baseline. The data was submitted to analysis of variance of repeated measures (ANOVA), followed by a Holm-Sidak (normal distribution) test or Mann Whitney (parametrics) test when suitable, with a significance level of 5%. All maximum vasoconstriction results presented dosage-dependant behavior, however, for the four groups tested, the vasoconstrictive result for epinephrine was significantly superior to felypressin (p<0,05). Diabetes and hypertension significantly reducedepinephrine and felypressin vasoconstrictor responses, integral above baseline, respectively, for control, diabetic, hypertensive and hypertensive-diabetic groups:2462±465; 1511±236; 2542± 5456 e 3749±819 mmHg.s (p<0.05, epinephrine) and 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0.05, felypressin). Both diabetes and hypertension, associated or not, significantly increased time necessary to achieve maximum vasoconstrictor response and its duration (p<0,05). Diabetic, hypertensive and hypertensive-diabetic mesenteric arteries presented 1A-adrenoceptor, AT1B and AT2 angiotensin II-receptor gene expression significantly increased when compared with control group (p<0,05), while AT1Areceptor presented this pattern only in diabetic groups.1A-adrenoceptor gene expression did not confirm functional data, probably due to chronic disease state in wich PCR was performed. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em ratos hipertensos e diabéticos não tratados, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.Its possible to correlate our datawith reducedvasoconstrictor activity of felypressinin clinical use. Increased sensibility and receptor population for vasoconstrictor endogenous molecules could explain diabetic populations tendency to develop arterial hypertension. Our results suggest that epinephrine is more potent than felypressin and both vasoconstrictors presents reduced effects on diabetic and hypertensive patients, what reinforces vasoconstrictor associated with local anesthetic use in this population.

O presente trabalho teve como objetivo associar modelos indutivos de diabetes e hipertensão, analisar e comparar o efeito de agentes vasoconstritores presentes nas soluções anestésicas locais, injetados por via intravenosa nas doses de 80, 160, 320, 640 e 1280ng (adrenalina) ou 0,125; 0,25; 0,5; 1; 2 e 3 x10-3UI (felipressina), sobre a pressão arterial de ratos normotensos, diabéticos, hipertensos renais um-rim, um clip (1R-1C) e hipertensos1R-1C-diabéticos, além de verificar a glicemia após injeção de doses correspondentes a 20 e 80% da resposta pressora máxima. Ratos Wistar machos pesando 110-160g, foram anestesiados com mistura de quetamina e xilazina (50+10mg/ml/kg de peso), tiveram seu abdômen aberto e receberam um clip de prata com abertura 0,25mm na artéria renal esquerda, removendo-se cirurgicamente o rim direito (ratos 1R-1C). Após 14 dias, receberam injeção subcutânea de estreptozotocina (50 e 60mg/kg de peso) para indução do diabetes mellitus sendo a glicemia testada pela veia caudal previamente aos experimentos (diabéticos). Após 28 dias da implantação do clip, todos os grupos foram novamente anestesiados e implantaram-se cânulas de polietileno (PE-50) na artéria carótida esquerda e veia jugular direita, para registro direto da pressão arterial e injeção de drogas, respectivamente. Animais controle sofreram cirurgia sem implantação do clip (normotensos). O cateter arterial foi conectado ao sistema de registro computadorizado (PowerLab®) utilizando software específico (Chart 5Pro®). A pressão arterial registrada durante os primeiros 5 minutos foi considerada como valor basal. Analisaram-se: a integral da resposta, menor resposta hipotensora, maior resposta hipertensora, duração e intervalo de tempo para atingir respostas máxima e mínima, em todos os grupos, para cada dose injetada dos dois vasoconstritores. No dia seguinte, foi medida a glicemia inicial e após a injeção das doses de 160 e 640ng (adrenalina) ou 0,25 e 2 x10-3UI (felipressina). Os dados foram submetidos à análise de variância de medidas repetidas (ANOVA), seguida do teste de Holm-Sidak (distribuição normal) ou de Mann-Whitney (paramétrico), quando apropriado, nível de significância de 5%. A felipressina, ao contrário da adrenalina, não apresentou ação hipotensora além de apresentar menor efeito hipertensor global e maior duração da resposta. Animais diabéticos e hipertensosdiabéticos apresentaram menor resposta hipotensora à adrenalina, maior resposta hipertensora e respostas significativamente mais duradouras, evidenciando maior sensibilidade aos efeitos deste vasoconstritor. Animais hipertensos apresentaram aumento da integral das respostas, especialmente com grandes doses, evidenciando maior sensibilidade aos efeitos da administração exógena de adrenalina. Nos animais hipertensos-diabéticos a resposta pressora à felipressina foi potencializada. Animais diabéticos e hipertensos-diabéticos apresentaram resposta hiperglicêmica após injeção de 640ng de adrenalina, enquanto apenas o grupo de hipertensos-diabéticos apresentou elevação da glicemia após injeções de ambas as doses de felipressina. Os resultados apontam, de modo geral, para um aumento da sensibilidade aos agentes vasoconstritores na presença simultânea de hipertensão e diabetes. Além disso, somente os hipertensos-diabéticos tiveram elevação da glicemia após injeção de doses baixas de felipressina (0,25mUI). Entretanto, a felipressina demonstrou menores picos hipertensivos, apesar de sua longa duração, nos grupos estudados, o que a coloca como um possível vasoconstritor a ser utilizado em portadores de cardiopatias, incluindo diabéticos. / The present study was designed to induce arterial hypertension associated with diabetes mellitus, analyze and compare the effects of vasoconstrictors drugs, presents in anesthetic cartridge, injected by intravenous route (IV), in doses of 80, 160, 320, 640 and 1280ng (epinephrine) or 0,125; 0,25; 0,5; 1; 2 e 3x10-3UI (felypressin) on arterial pressure (AP) of normotensive, diabetic, one-kidney,one-clip (1K-1C) hypertensive and 1K-1C hypertensive-diabetic rats. The blood glucose levels were determined after IV injection of both drugs in doses that produced 20 and 80% of maximal pressure response. Male Wistar rats weighing 110-160g were anesthetized with a ketamine and xylazine mixture (50+10mg/ml/kg de peso). After abdominal incision, a silver clip with 0.25-mm gap was implanted in the main left renal artery and right kidney was removed (1K-1C rats). Fourteen days after, some animals received subcutaneous injection of streptozotocin (50 and 60mg/kg weight) to induce diabetes mellitus. Tail blood glucose was tested before experiments (diabetics rats). Four weeks after clip implantation all rats were anesthetized again and a catheter (PE50) was inserted into the left carotid artery and right jugular vein, respectively to obtain a direct arterial pressure register and to inject drugs. Control groups were submitted to surgery procedures without clip installation (normotensive). The arterial catheter was then connected to the transducer and to the computer register system (PowerLab®) using a Chart 5 Pro® software. The AP registered in the first five minutes was considered as a basal value. The following parameters were registered: integral of complete response, minimal hypotensive response, maximal hypertensive response, response length (duration) and duration of time to attain maximum and minimum responses, in all animals groups, to every injected dose of both vasoconstrictor drugs. In the next day blood glucose levels were determined initially and after venous injection of 160 e 640ng (adrenaline) or 0,25 an 2 x10-3UI (felipressin). Data were analyzed by one and two ways repeated measures ANOVA followed by Holm-Sidak (normal distribution) or Mann-Whitney (parametric) test, when appropriated. The significance level was 5%. Felypressin didnt show hypotensive effects and produced lower hypertensive responses with prolonged time lengths when compared with epinephrine. The hypotensive response to epinephrine was reduced in diabetic and hypertensive-diabetic rats, and the hypertensive responses were higher and prolonged. These results together suggest increased sensibility to the pressure effects of epinephrine. Hypertensive rats showed increased integral of pressures responses, especially in higher doses, also suggesting increased sensibility to epinephrine. Felypressin responses were potentiated in hypertensive-diabetic group. Diabetic and hypertensive-diabetic rats showed increased blood glucose levels after 640ng epinephrine injection, whereas only hypertensive-diabetic rats had increased values of blood glucose after felypressin injections, at both doses. These results together indicate increased sensibility to both drugs in diabetes association with arterial hypertension. Felypressin presented less hypertensive peak and longer length of activity in all studied groups, what suggests that felypressin, in the concentration used in dental anesthetic solutions, may be a secure vasoconstrictor drug in cardiac patients, including diabetics.

O presente trabalho teve como objetivo analisar e comparar o efeito de agentes vasoconstrictores presentes nas soluções anestésicas locais, injetados por via intravenosa nas doses de 80, 160, 320, 640 e 1280 ng (adrenalina) ou 0.5, 1, 2, 3 e 4 UI (felipressina), sobre a pressão arterial de ratos, hipertensos renais um-rim, um clip (1R-1C) e 1R-1C tratados com atenolol, comparando com animais nomotensos de mesmo peso e lote. Ratos Wistar machos pesando 150g, foram anestesiados com mistura de igual quantidade de quetamina e xilazina (1mL da mistura/kg), tiveram seu abdômen aberto e receberam um clip de prata com abertura 0,25mm na artéria renal esquerda, removendo-se cirurgicamente o rim direito (ratos 1R-1C). Alguns desses animais, depois de 14 dias, tiveram sua pressão sistólica indireta registrada pela pletsmografia de cauda e começaram a receber tratamento com atenolol (90 mg/kg/dia) por gavage (1R-1C tratados). Após 28 dias da implantação do clip, todos os grupos foram novamente anestesiados e implantaram-se cânulas de polietileno (PE-50) na artéria carótida esquerda e veia jugular direita, para registro direto da pressão arterial e injeção de drogas, respectivamente. Animais de mesmo lote e peso serviram como controle (normotensos). O catéter arterial foi então conectadas ao sistema de registro computadorizado (PowerLab®) utilizando software específico (Chart 5Pro ®). A pressão arterial (PA) e frequência cardíaca (FC) registradas durante os primeiros 5 minutos, foram consideradas como valores basais. Analisaram-se: a menor resposta hipotensora, maior resposta hipertensora, freqüência cardíaca média e duração da resposta, nos três grupos de animais, para cada dose injetada dos dois vasoconstrictores. Os dados foram submetidos à análise de variância de medidas repetidas (ANOVA), seguida do teste de Holm-Sidak ou de Mann-Whitney, quando apropriado, a um nível de significância de 5%. A felipressina, ao contrário da adrenalina, não apresentou ação hipotensora; por outro lado, ambas apresentaram respostas hipertensoras de magnitude semelhante nos 3 grupos de animais, notando-se tendência para menores respostas nos animais tratados com atenolol. A felipressina provocou queda de FC significativa (p<0,01) nos animais normotensos e tratados, causando aumento de FC nos hipertensos apenas com as maiores doses, enquanto que a adrenalina provocou aumento de FC dose-dependente nos normotensos e hipertensos, sem promover alteração da FC nos ratos tratados. A duração da resposta hipertensora provocada pela felipressina foi significativamente maior que a provocada pela adrenalina (p<0,01) em todos os grupos de animais, indicando possível efeito vasoconstrictor prolongado. Os resultados permitem afirmar que a felipressina apresenta ações semelhantes à adrenalina, com resposta hipertensora mais prolongada, nas populações de animais analisadas. Em função das doses e da via empregada nesse estudo, pode-se sugerir que a felipressina é bastante segura para populações hipertensas ou que estejam recebendo atenolol. / The present study was designed to analyze and compare the effects of some vasoconstrictors, injected by intravenous route in the doses of 80, 160, 320, 640 and 1280 ng (epinephrine) or 0.5, 1, 2, 3 and 4 IU (felypressin) upon the arterial pressure of normotensive, 1K-1C hypertensive and 1K-1C rats treated with atenolol. Male Wistar rats weighting 150g were anesthetized with a mixture of equal proportion of ketamine and xylazine by intraperitonial injection (1mL/kg) and 1K1C hypertension was surgically induced by means of partial constriction of the main left renal artery with a silver clip with a 0.25-mm gap. The right kidney was surgically removed. Fourteen days after surgical procedures arterial pressure (AP) was indirectly measured (tail cuff method) to monitor the development of hypertension. Only 1K1C rats with AP more than 150mm Hg were included in the protocol and received by gavage (1mL/d), for the next 14 days, atenolol (90 mg/kg/day). The treatments were carried out always between 8 and 9 AM. Four weeks after the surgical procedure all rats were anesthetized again with the same mixture and a catheter (PE50) was inserted into the left carotid artery and right jugular vein, respectively to obtain a AP register and to inject drugs. The arterial catheter was then connect to the transducer and to computer register system (PowerLab®) using a Chart 5 Pro® software. The AP and heart rate (HR) registered in the first five minutes were considered basal values. The following parameters were registered: minimal hypotensive response, maximal hypertensive response, mean HR and response lenght (duration), in all animals groups, to every injected dose of epinephrine and felypressin. The data were analyzed by two ways repeated measures ANOVA followed by Holm-Sidak or Mann-Whitney test, when appropriated. The significance level was 5%. Epinephrine, but not felypressin, presents some hypotensive action with the lowest doses. However, both of them present hypertensive responses of same magnitudes in all groups, with non-significant reduced responses noted in the 1K-1C atenolol group. The HR was significantly lowered by felypressin in the normotensive and 1K-1C atenolol group; this vasoconstrictor agent produced elevated HR in hypertensive rats only with the greatest doses. Epinephrine caused dose-dependent increases in HR in normotensive and 1K-1C without modifying the HR of 1K-1C atenolol treated rats. The felypressin response length were significantly longer than that produced by epinephrine in all groups (p<0,01), indicating a prolonged vasoconstrictor effect. Our results suggest that felypressin has equipotent pressure responses when compared with epinephrine, showing greater extent of action. Considering the administration route, the doses used in this study and the concentration in local anesthetics cartridges, we suggest that felypressin was safe enough to be one of the vasoconstrictors of choice in hypertensive subjects and in those who received atenolol as a medication to lower their pressure.

The vivid memory of an emotional event, as well as memory for incidental details associated with the arousing event, has been referred to collectively as a “flashbulb memory”. An important aspect of flashbulb memory in people is that an emotional event enhances memory of contextual details, such as the weather, or clothes one was wearing at the time of the event. Therefore, an emotional event not only produces a detailed memory of the event, itself, but also enhances memory for contextual details that would otherwise not be remembered. The first goal of this work is to describe the development of my animal model of flashbulb memory, including a discussion of the importance of the timing between an emotional event and incidental, contextual cues. The second goal is to address the time-dependent neuroendocrine processes involved in stress-induced memory enhancement in rats. The involvement of brain structures, namely the hippocampus and amygdala, and hormones, including corticosterone and epinephrine, that interact to produce a composite memory of the contextual cues occurring in close temporal proximity to an emotional event are discussed. The results of Experiment 1 validate the animal model of flashbulb memory whereby an emotional event (predator exposure) produced memory for context cues that, under control conditions, would be forgotten. This memory enhancement only occurred when the emotional event was close in temporal proximity to training in the task. Experiment 2 provided evidence that epinephrine administration close in time to training mimicked the context memory formation induced by brief predator exposure, while propranolol, a β-adrenergic antagonist, as well as CPP, an NMDA receptor antagonist, blocked this effect. The results of Experiment 3 revealed that propranolol, CPP, and dexamethasone also blocked the brief predator stress-induced context memory formation. The results of Experiment 4 revealed that cannulated animals infused with aCSF (control) did not show evidence of predator stress-induced memory, therefore methodological issues within this experiment are addressed. Finally, the results of Experiment 5 revealed that adrenalectomy eliminated the predator stress-induced context memory compared to sham operated animals, suggesting that endogenous stress hormones are required for stress-induced context memory formation. Further, adrenalectomized rats supplemented with epinephrine before training did show evidence of context memory enhancement suggesting that epinephrine eliminated the memory impairment produced by adrenalectomy, and was sufficient to enhance memory in the absence of corticosterone. Overall this approach has provided insight into the time-dependent neuroendocrine processes involved in the formation of flashbulb, and potentially traumatic, memories in people.

Around the time of birth, the lung switches from a secretory- to a liquid absorptive organ to enable the fetus to transit from an intra-uterine to an air-breathing environment. This study concerns hormonal control of the liquid reabsorptive mechanism in the fetal lung which allows this transition to take place. Thyroidectomy in the fetal sheep at 118 days gestation (term = 147 days) prevented the development of adrenaline- or cyclic AMP-sensitivity which, in euthyroid fetuses, resulted in the capacity to absorb lung liquid from 130 days onwards. Studies in which T₃ and T₄ were infused to thyroidectornized fetal sheep showed that T₃ was required for the normal evolution of the reabsorptive response. However, infusion of this hormone to immature fetuses (110 days) did not advance the gestation at which adrenaline-sensitive absorption is first seen. Co-infusion of T₃ and hydrocortisone showed that these 2 hormones have a powerful synergistic effect on the absorption mechanism. Within a few hours of infusion of these 2 hormones to immature fetuses, a reabsorptive response to adrenaline similar to that normally seen in mature fetuses was observed. This response was fully reversible on withdrawal of T₃ and hydrocortisone infusion, and the hormonal effect was blocked by the protein synthesis inhibitor, cyclohexirnide. These findings suggest that the normal rise in T₃ and cortisol seen in the fetus in late gestation is responsible for maturation of the liquid absorption mechanism which allows the fetus to make a transition to an independent air-breathing existence. These observations may be of significance in the clinical management of infants born prematurely, who may have had insufficient pre-natal exposure to T₃ and cortisol.

No presenta resumen. / Revisión por pares

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19609号 / 医博第4116号 / 新制||医||1015(附属図書館) / 32645 / 京都大学大学院医学研究科医学専攻 / (主査)教授 岩井 一宏, 教授 小杉 眞司, 教授 瀬原 淳子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM