Orientador: Elizete Aparecida Lomazi da Costa Pinto / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T22:39:31Z (GMT). No. of bitstreams: 1 Fernandes_VanessaPaciniInaba_M.pdf: 849519 bytes, checksum: f4dae55b9aff4fa63a90c060178a1915 (MD5) Previous issue date: 2009 / Resumo: Distúrbios da motilidade do trato digestório podem estar envolvidos na fisiopatologia da constipação funcional. Retarde no esvaziamento gástrico tem sido observado em associação à constipação funcional e a relação de causa e efeito entre as condições não está definida. O objetivo desse estudo foi avaliar a motilidade gástrica antes da remoção da impactação fecal e após a regularização do hábito intestinal em crianças com constipação funcional. Casuística e métodos: Crianças (N= 22; 18 meninos, 10±2,2 anos) com constipação funcional e escape fecal retentivo, início da constipação aos 6,8±1,6 anos, acompanhadas no ambulatório de gastropediatria do Hospital das Clinicas da Universidade de Campinas. Estudo prospectivo, desenvolvido no período de 2000 a 2003. Os sintomas gastrintestinais foram registrados e estudos de esvaziamento gástrico foram conduzidos antes da remoção da impactação fecal (EG1) e após a regularização do hábito intestinal (EG2). O esvaziamento gástrico foi avaliado por método cintilográfico usando volumes individualizados de água. O T ½ do esvaziamento gástrico foi obtido para todos os pacientes nos dois momentos. Resultados: Vinte e um pacientes relataram sintomas gastrintestinais ao início do estudo, mais comumente dor abdominal após a ingestão de alimentos. A maioria dos pacientes relatou melhora desses sintomas com o tratamento da constipação. Não houve diferença significativa entre as médias de T ½ do esvaziamento gástrico nos tempos EG1 (32,8 ± 24,8 minutos) e EG2 (25,8 ±10,5 minutos), realizados com intervalo de 12 ± 5 semanas, p=0,09. Houve correlação positiva entre o tempo para recuperação da constipação e EG1(R=0,61, p=0,01) e EG2 (R=0,58, p=0,01). Conclusão: Pacientes pediátricos com constipação funcional crônica grave apresentaram tempo de esvaziamento gástrico prolongado ao início do tratamento e após a regularização do hábito intestinal. O tempo para recuperação da constipação correlacionou-se positivamente com os valores de esvaziamento gástrico. Palavras-chave: constipação funcional, impactação fecal, escape fecal retentivo, esvaziamento gástrico, cintilografia / Abstract: Gastrointestinal motility disorders may be at the basis of constipation. Gastric emptying delay has been reported in constipated patients and a causality relation is still not outlined. The objective of this study was to evaluate pre- and post-treatment gastric emptying values and dyspeptic symptoms in a group of children with functional constipation and fecal retention. Methods: Twenty-two children (eighteen boys, median age 10±2.2 years) with chronic constipation, fecal retention and soiling were seen in a tertiary pediatric gastroenterology clinic. Gastric emptying (GE) T1/2 was measured by scintigraphy before fecal impaction removal (GE1) and repeated (GE2) when patients recovered regular bowel movements (12±5 weeks after GE1). Patients were followed until complete relieve of constipation (11.6 ± 5.7 months). Gastric half-emptying time of a liquid meal (water) was measured using a radionuclide technique, reference value t ½ 12 ± 3 minutes. Results: Twenty-one children reported symptoms related to food ingestion, which were completely relieved after resuming regular bowel movements. Mean GE1 was 32.8 ± 24.8 minutes and mean GE2 was 25.8 ±10.5 minutes. There was no significant difference between GE1 and GE2 (p=0,09). There was significant correlation between mean time to resume regular bowel movements and gastric emptying values GE1 (R=0,61, p=0,01) and GE2 (R=0,58, p=0,01). Conclusion: The results of the present study indicate that slow gastric emptying is a common feature among children with chronic constipation and fecal impaction, and that this correlates with a slow response to therapy. Resuming of satisfactory bowel function did not result in normalization of gastric emptying studies. Key words: functional constipation, fecal retention, soiling, gastric emptying, scintigraphy / Mestrado / Pediatria / Mestre em Saude da Criança e do Adolescente

No description available.

<p>  </p> <p>The world has experienced an unprecedented change in the systems responsible for food production, distribution, and commercialization with concurrent changes in diets. In developed and developing countries, the shift in consumption patterns has moved towards a Western diet pattern which has been linked to negative health outcomes including obesity, diabetes and associated non-communicable diseases. Traditional African diets have previously been associated with protective effects against the development of the above-mentioned conditions. Yet, the underlying reasons for this is not clear. One dietary factor that may contribute to its protective effect is the principal available carbohydrate, starch, which in traditional African staples is considered to contain slowly digestible carbohydrates (SDCs) and some amount of resistant starch (RS). We reported that traditional African staple starchy foods (sorghum and millet) had markedly slower gastric emptying than introduced modern starchy foods (rice, pasta and potatoes). This response was attributed to activation of enteroendocrine cells of the small intestine (L-cells) with potential to trigger physiological, hormonal, and neurological processes that affect digestion time and perception of hunger; effect known as the ileal brake. Moreover, at least in mice models, consumption of SDCs has shown to have beneficial effects on the rate and type of fuel (e.g. carbohydrate vs fat) used for metabolic processes.</p> <p>The first thesis study compared the effect of diets (cohorts in the USA and Kenya) on gastric half-emptying time and metabolic fuel utilization in healthy adults. Our findings showed that gastric emptying time was not different between cohorts and that diet did not influence gastric emptying time; however, calculated respiratory exchange ratio (RER) (which is a measure of metabolic fuel utilization at the cellular level, e.g. carbohydrate vs fat) and metabolic flexibility (which is the ability to switch between metabolic fuel sources upon demand or need) was higher for the Kenyan cohort. Multivariant models were developed and corrected for multicollinearity of some diet variables. Carbohydrate and protein in multivariate model 1; total fiber, added sugars and starch in multivariate model 2; and diet quality (measured as the Healthy Eating Index based on 2015-2020 dietary guidelines, or HEI-2015) in multivariate model 3, were significantly and independently correlated with RER and metabolic flexibility.   </p> <p>The second study assessed if slow gastric emptying and improve metabolic fuel utilization could be induced through SDC supplementation. The objective of this study was to determine if continual consumption of SDC for 21 days delayed the rate of gastric emptying, moderated postprandial glycemic response, decreased hunger, and/or improved metabolic fuel utilization in subjects with low diet quality (HEI-2015<65). Our results indicated that supplementation with SDC did not slow gastric emptying time or acute measures of metabolic fuel utilization; however, continuous consumption of SDC had a modest but significant effect on improving metabolic flexibility and decreasing hunger scores. </p> <p>The last two chapters of this thesis focused on the use of a low-cost, high-pressure, high temperature extruder suitable for processing in Africa of whole grain pearl millet (<em>Pennisetum glaucum</em>). In Africa, emerging, entrepreneurial companies are increasingly gaining share of local markets by manufacturing and distributing high-quality locally sourced processed foods made with indigenous grains. Whole pearl millet is particularly susceptible to development of rancidity. The objective of our third study was to assess the use of the extruder on the stability and sensory attributes of whole grain pearl millet extruded flours to be used for instant thin and thick porridges. Findings showed that extrusion fully gelatinized the starch in pearl millet and prevented hydrolytic rancidity in the instant flour products. However, extrusion cooking did not stop oxidative rancidity. We concluded that while extrusion cooking is a versatile technology for whole grain processing, refinement of extrusion conditions used in the experiment and the evaluation of other unit operations (e.g. steeping, germination) in combination with extrusion cooking may improve the sensory properties of final products.</p> <p>Finally, extrusion cooking has been showed to promote the formation of beneficial amylose-lipid complexes (ALCs). The objective of the last study was to evaluate the formation of ALCs in whole grain pearl millet extruded flours, characterize their composition, and assess their ability to slowly digest <em>in vitro</em>. Extrusion promoted the formation ALCs and these flours exhibited a slow enzymatic digestion <em>in vitro</em>. The findings from this thesis provide insights into the role of diets and metabolic fuel utilization, and improvement of processed pearl millet foods in Africa.</p>

A intolerância gástrica em recém-nascidos prematuros constitui um grande desafio no cuidado neonatal, levando ao uso prolongado de nutrição parenteral e cateteres venosos centrais, aumentando a taxa de infecções neonatais graves e o tempo internação hospitalar dessas crianças. O atraso na maturação da função motora é apontado com o fator determinante da intolerância alimentar dessa faixa etária e a presença de resíduos gástricos a sua principal manifestação clínica. Estudos em adultos mostraram que a velocidade de esvaziamento gástrico é volume dependente, mas em recém-nascidos prematuros este fator não foi adequadamente estudado. O objetivo desse estudo foi avaliar a correlação entre velocidade de esvaziamento gástrico e volume gástrico (em recém-nascidos humanos e ratos), avaliar a influência de fatores pré, peri e pós-natais no esvaziamento gástrico (em recém-nascidos humanos) e estudar os mecanismos fisiológicos que poderiam explicar o efeito do volume na velocidade de esvaziamento gástrico (em ratos). No estudo em humanos, foi realizada a medida da velocidade de esvaziamento gástrico de 20 crianças com idade gestacional entre 28 e 32 semanas através de ultrassonografia, realizada antes e depois da infusão da dieta por sonda orogástrica no primeiro mês de vida. No estudo animal, foi avaliada a velocidade de esvaziamento gástrico de 89 ratos com idade entre 1 e 21 dias através em diferentes tempos de separação materna. Em ambos estudos foi utilizado método de ultrassonografia para estimativa dos valores de esvaziamento gástrico. No modelo animal foram realizadas também medidas de força de contração muscular para diferentes graus de estiramento da parede gástrica. A velocidade de esvaziamento gástrico mostrou correlação importante com o volume gástrico em humanos ((R2 = 0,66 p<0,01) e em ratos (R2 = 0,43 p<0,01) e as crianças com mais de uma semana de vida esvaziam em média 50% do volume oferecido nos primeiros 30 minutos após o término da mamada. As medidas in vitro em ratos mostraram que a contração muscular gástrica induzida por agonista foi diretamente proporcional ao grau do estiramento da parede gástrica e foram mediadas através da via ROCK-2. Em recém-nascidos humanos e ratos o volume gástrico é fator determinante da velocidade de esvaziamento gástrico. Nos ratos, o esvaziamento gástrico não é dependente da idade, mas sim do volume gástrico através da ativação da via ROCK-2, estimulada pelo estiramento da parede gástrica. Em humanos, tipo de leite, uso de ventilação mecânica, tipo de parto, uso de corticosteroide antenatal, uso de antibióticos e/ou antifúngicos, uso de fototerapia não influenciaram a velocidade de esvaziamento gástrico. / Feeding intolerance in preterm infants is a major challenge in neonatal care, leading to a prolonged use of parenteral nutrition and central venous catheters, increasing the rate of severe neonatal infections and the length of hospital stay of these infants. The delay in the maturation of motor function is indicated with the determinant factor of the feeding intolerance of this age group and the presence of gastric residuals its main clinical manifestation. Studies in adults have shown that the rate of gastric emptying is volume dependent. But in preterm infants, this factor has not been adequately addressed. The objective of this study was to evaluate the correlation between gastric emptying rate and gastric volume (in human and rat neonates), to evaluate the influence of pre, peri and postnatal factors on gastric emptying (in human newborns) and to study the physiological mechanisms that could explain the effect of volume on gastric emptying rate (in rats). In the human study, the gastric emptying rate of 20 children with gestational age between 28 and 32 weeks was measured by ultrasonography performed before and after infusion of the diet by gavage in the first month of life. In the animal study, the gastric emptying rate of 89 rats aged 1 to 21 days through at different times of maternal separation was evaluated. In both studies, an ultrasound method was used to estimate gastric emptying values. In the animal model muscle strength measurements were also performed for different degrees of gastric wall stretching. Gastric emptying rate showed a significant correlation with the gastric volume in humans ((R2 = 0.66 p <0.01) and in rats (R2 = 0.43 p <0.01) and in the 30 minutes after feeding 50% of the volume had been emptied. In vitro measurements in rats showed that gastric muscle contraction induced by agonist was directly proportional to the degree of gastric wall stretching and were mediated via upregulation of ROCK-2 activity. In human and rat neonates, the gastric volume is a determinant of gastric emptying rate. In rats, gastric emptying is unrelated to postnatal age but dependent on gastric volume, through the activation of the ROCK-2 pathway, wall strain-induced. In humans, milk type, use of mechanical ventilation, type of delivery, use of antenatal corticosteroids, use of antibiotics and/or antifungals, phototherapy use did not influence gastric emptying rate.

A intolerância gástrica em recém-nascidos prematuros constitui um grande desafio no cuidado neonatal, levando ao uso prolongado de nutrição parenteral e cateteres venosos centrais, aumentando a taxa de infecções neonatais graves e o tempo internação hospitalar dessas crianças. O atraso na maturação da função motora é apontado com o fator determinante da intolerância alimentar dessa faixa etária e a presença de resíduos gástricos a sua principal manifestação clínica. Estudos em adultos mostraram que a velocidade de esvaziamento gástrico é volume dependente, mas em recém-nascidos prematuros este fator não foi adequadamente estudado. O objetivo desse estudo foi avaliar a correlação entre velocidade de esvaziamento gástrico e volume gástrico (em recém-nascidos humanos e ratos), avaliar a influência de fatores pré, peri e pós-natais no esvaziamento gástrico (em recém-nascidos humanos) e estudar os mecanismos fisiológicos que poderiam explicar o efeito do volume na velocidade de esvaziamento gástrico (em ratos). No estudo em humanos, foi realizada a medida da velocidade de esvaziamento gástrico de 20 crianças com idade gestacional entre 28 e 32 semanas através de ultrassonografia, realizada antes e depois da infusão da dieta por sonda orogástrica no primeiro mês de vida. No estudo animal, foi avaliada a velocidade de esvaziamento gástrico de 89 ratos com idade entre 1 e 21 dias através em diferentes tempos de separação materna. Em ambos estudos foi utilizado método de ultrassonografia para estimativa dos valores de esvaziamento gástrico. No modelo animal foram realizadas também medidas de força de contração muscular para diferentes graus de estiramento da parede gástrica. A velocidade de esvaziamento gástrico mostrou correlação importante com o volume gástrico em humanos ((R2 = 0,66 p<0,01) e em ratos (R2 = 0,43 p<0,01) e as crianças com mais de uma semana de vida esvaziam em média 50% do volume oferecido nos primeiros 30 minutos após o término da mamada. As medidas in vitro em ratos mostraram que a contração muscular gástrica induzida por agonista foi diretamente proporcional ao grau do estiramento da parede gástrica e foram mediadas através da via ROCK-2. Em recém-nascidos humanos e ratos o volume gástrico é fator determinante da velocidade de esvaziamento gástrico. Nos ratos, o esvaziamento gástrico não é dependente da idade, mas sim do volume gástrico através da ativação da via ROCK-2, estimulada pelo estiramento da parede gástrica. Em humanos, tipo de leite, uso de ventilação mecânica, tipo de parto, uso de corticosteroide antenatal, uso de antibióticos e/ou antifúngicos, uso de fototerapia não influenciaram a velocidade de esvaziamento gástrico. / Feeding intolerance in preterm infants is a major challenge in neonatal care, leading to a prolonged use of parenteral nutrition and central venous catheters, increasing the rate of severe neonatal infections and the length of hospital stay of these infants. The delay in the maturation of motor function is indicated with the determinant factor of the feeding intolerance of this age group and the presence of gastric residuals its main clinical manifestation. Studies in adults have shown that the rate of gastric emptying is volume dependent. But in preterm infants, this factor has not been adequately addressed. The objective of this study was to evaluate the correlation between gastric emptying rate and gastric volume (in human and rat neonates), to evaluate the influence of pre, peri and postnatal factors on gastric emptying (in human newborns) and to study the physiological mechanisms that could explain the effect of volume on gastric emptying rate (in rats). In the human study, the gastric emptying rate of 20 children with gestational age between 28 and 32 weeks was measured by ultrasonography performed before and after infusion of the diet by gavage in the first month of life. In the animal study, the gastric emptying rate of 89 rats aged 1 to 21 days through at different times of maternal separation was evaluated. In both studies, an ultrasound method was used to estimate gastric emptying values. In the animal model muscle strength measurements were also performed for different degrees of gastric wall stretching. Gastric emptying rate showed a significant correlation with the gastric volume in humans ((R2 = 0.66 p <0.01) and in rats (R2 = 0.43 p <0.01) and in the 30 minutes after feeding 50% of the volume had been emptied. In vitro measurements in rats showed that gastric muscle contraction induced by agonist was directly proportional to the degree of gastric wall stretching and were mediated via upregulation of ROCK-2 activity. In human and rat neonates, the gastric volume is a determinant of gastric emptying rate. In rats, gastric emptying is unrelated to postnatal age but dependent on gastric volume, through the activation of the ROCK-2 pathway, wall strain-induced. In humans, milk type, use of mechanical ventilation, type of delivery, use of antenatal corticosteroids, use of antibiotics and/or antifungals, phototherapy use did not influence gastric emptying rate.

This thesis presents studies relating to the role of the gastrointestinal tract in postprandial blood pressure regulation. The areas that have been addressed include : ( i ) the methodological approaches to the evaluation of gastric emptying, blood pressure, splanchnic blood flow, intraluminal manometry and gut hormones and ( ii ) the pathophysiological mechanisms underlying postprandial hypotension, with a particular focus on ' gastric ' and ' small intestinal ' mechanisms and their potential therapeutic relevance. All of the studies have been either published or manuscripts have been prepared for publication. While scintigraphy represents the ' gold standard ' for the measurement of gastric emptying, recent studies suggest that three - dimensional ( 3D ) ultrasonography may also allow a precise measure of gastric emptying. Concurrent scintigraphic and ultrasonographic measurements of gastric emptying of liquids were performed in healthy young volunteers. There was a good correlation and agreement between scintigraphic measurements of gastric emptying and 3D ultrasonography after ingestion of both low - and high - nutrient drinks, indicating that 3D ultrasonography, provides a valid measure of gastric emptying of liquid meals in normal subjects. Postprandial hypotension, defined as a fall in systolic blood pressure of ≥ 20mmHg,occurring within two hours of a meal is now recognised as an important clinical problem, particularly in the elderly and in patients with type 2 diabetes. The mechanisms mediating postprandial hypotension are poorly understood. The effects of variations in concentration of intraduodenal glucose on the magnitude of the fall in blood pressure were evaluated in healthy elderly subjects. Blood pressure fell, and heart rate and blood glucose increased over time during infusions, however, there was no difference in blood pressure, heart rate or blood glucose concentrations between the study days. These observations suggest that glucose induced postprandial hypotension is a load rather, than concentration, dependent phenomenon. The effect of meal composition has been reported to influence the hypotensive response to a meal and information relating to the effects of triglyceride and protein on blood pressure is inconsistent. The comparative effects of isocaloric and isovolaemic intraduodenal infusions of glucose, triglyceride and protein on the magnitude of the postprandial fall in blood pressure and rise in heart rate and superior mesenteric artery blood flow were evaluated in healthy elderly subjects. There were comparable falls in systolic blood pressure and rises in heart rate, however, the maximum fall in systolic blood pressure occurred later after triglyceride and protein and the stimulation of superior mesenteric artery blood flow was less after protein. These observations suggest that the relatively slower systolic blood pressure response after triglyceride and protein may potentially reflect the time taken for digestion of triglyceride to free fatty acids and protein to amino acids. Acarbose is an antidiabetic drug that slows both gastric emptying and small intestinal glucose absorption. The effects of acarbose, on blood pressure, heart rate, gastric emptying of, and the glycaemic, insulin, glucagon - like peptide - 1 ( GLP - 1 ) and glucosedependent insulinotropic - polypeptide ( GIP ) responses to, an oral sucrose load were evaluated in healthy elderly subjects. Acarbose attenuated the fall in blood pressure and increase in heart rate induced by oral sucrose. Acarbose slowed gastric emptying and was associated with increased retention in the distal stomach. Stimulation of GLP - 1 may contribute to the slowing of gastric emptying and suppression of postprandial glycaemia by acarbose. These findings suggest that acarbose may represent a therapeutic option for the treatment of patients with postprandial hypotension. Recent studies indicate that gastric distension attenuates the postprandial fall in blood pressure. The effects of gastric distension on blood pressure and heart rate during intraduodenal infusion of glucose at a constant load and concentration were evaluated in healthy elderly subjects. Intragastric administration of water markedly attenuated the falls in systolic and diastolic blood pressure induced by intraduodenal glucose. Heart rate increased, with and without gastric distension, in response to intraduodenal glucose infusion but not after intraduodenal saline infusion. This study suggests that gastric distension may potentially be used as a simple adjunctive treatment in the management of postprandial hypotension. Studies employing nitric oxide synthase blockers have established, in animals, that nitric oxide mechanisms are important in the regulation of splanchnic blood flow and, hence, may effect postprandial blood pressure. The role of the nitric oxide synthase inhibitor, NG - nitro - L - arginine - methyl - ester ( L - NAME ), on gastric emptying, postprandial blood pressure, plasma insulin concentration and incretin hormone ( ie GIP and GLP - 1 ) release, following an oral glucose load, were evaluated in healthy elderly subjects. L - NAME attenuated the postprandial fall in blood pressure and increase in heart rate but had no effect on gastric emptying of glucose. L - NAME attenuated the glucose - induced rise in plasma insulin but had no effect on the incretin ( GIP and GLP - 1 ) hormone response to oral glucose. The study indicates that the magnitude of the fall in blood pressure and increase in heart rate and stimulation of insulin secretion induced by oral glucose in healthy elderly subjects are mediated by nitric oxide mechanisms by an effect unrelated to changes in gastric emptying, or the secretion of GIP and GLP - 1. Studies utilising 5 - hydroxytryptamine ( 5 - HT ) infusions in animals have demonstrated regional variations in intestinal blood flow suggesting a role for 5 - HT in postprandial haemodynamic responses. The effects of the 5 - hydroxytryptamine 3 ( 5 - HT3 ) antagonist, granisetron, on the blood pressure, heart rate, antropyloroduodenal motility and glycaemic responses to intraduodenal glucose infusion were assessed in healthy elderly subjects. Granisetron had no effect on blood pressure, heart rate or antral and pyloric motor responses but modulated the duodenal motor response, to intraduodenal glucose. This study indicates that while the cardiovascular response to intraduodenal glucose does not appear to be influenced by the stimulation of 5 - HT3 receptors, this receptor may be involved in the modulation of the duodenal motor activity. / Thesis (Ph.D.)--School of Medicine, 2006.

<p>Postoperative nausea and vomiting (PONV) is still a clinical problem and its incidence is unacceptably high. After the introduction of propofol as an agent for induction and maintenance of anesthesia, it was reported that the incidence of PONV was lower. It was also proposed that propofol possesses antiemetic effects. Dopamine, serotonin and opioids may contribute to PONV. Therefore the purpose of these investigations was to evaluate if propofol has dopamine, serotonin or opioid antagonistic effects and if a subhypnotic infusion of propofol decreases the incidence of PONV. </p><p>Nausea and vomiting were induced in volunteers by a dopamine agonist, apomorphine, and by ipecacuanha which releases serotonin from the enterochromaffin cells in the gut. The effects of propofol on gastric emptying and orocecal transit time were evaluated in volunteers with the paracetamol method and by measuring the endtidal hydrogen concentration after ingestion of the trisaccharide raffinose. The effects of morphine on gastric emptying and gastric tone were studied in patients before surgery with the paracetamol method and with an electronic barostat, respectively. The effects of low dose propofol for prophylaxis of PONV were studied in 172 patients undergoing breast and abdominal surgery. Propofol prophylaxis was compared with a multidrug regimen consisting of dexamethasone and three antiemetic drugs, ondansetron, droperidol and metoclopramide. </p><p>Propofol did not abolish apomorphine-induced vomiting but reduced the number of retchings induced by ipecacuanha. Propofol sedation did not influence gastric emptying of liquids but it slightly prolonged orocecal transit time. Gastric relaxation induced by morphine was abolished by propofol but propofol did not abolish morphine-induced delay of gastric emptying. Propofol in a low dose infusion reduced the incidence of PONV but nausea and especially vomiting increased significantly after termination of the infusion. Pro- phylaxis with the multidrug regimen was very effective in preventing PONV. </p><p>These studies have shown that propofol does not have any dopamine antagonistic effect but may have a weak serotonin antagonistic effect. Propofol cannot abolish morphine-induced delay of gastric emptying. Low dose propofol infusion was effective in preventing PONV as long as the infusion was ongoing but after termination of the infusion nausea and especially vomiting substantially increased. The multidrug regimen (dexamethasone, ondansetron, droperidol, metoclopramide) was very effective in preventing PONV and can be recommended as prophylaxis in patient groups with a known high risk for PONV. </p>

Postoperative nausea and vomiting (PONV) is still a clinical problem and its incidence is unacceptably high. After the introduction of propofol as an agent for induction and maintenance of anesthesia, it was reported that the incidence of PONV was lower. It was also proposed that propofol possesses antiemetic effects. Dopamine, serotonin and opioids may contribute to PONV. Therefore the purpose of these investigations was to evaluate if propofol has dopamine, serotonin or opioid antagonistic effects and if a subhypnotic infusion of propofol decreases the incidence of PONV. Nausea and vomiting were induced in volunteers by a dopamine agonist, apomorphine, and by ipecacuanha which releases serotonin from the enterochromaffin cells in the gut. The effects of propofol on gastric emptying and orocecal transit time were evaluated in volunteers with the paracetamol method and by measuring the endtidal hydrogen concentration after ingestion of the trisaccharide raffinose. The effects of morphine on gastric emptying and gastric tone were studied in patients before surgery with the paracetamol method and with an electronic barostat, respectively. The effects of low dose propofol for prophylaxis of PONV were studied in 172 patients undergoing breast and abdominal surgery. Propofol prophylaxis was compared with a multidrug regimen consisting of dexamethasone and three antiemetic drugs, ondansetron, droperidol and metoclopramide. Propofol did not abolish apomorphine-induced vomiting but reduced the number of retchings induced by ipecacuanha. Propofol sedation did not influence gastric emptying of liquids but it slightly prolonged orocecal transit time. Gastric relaxation induced by morphine was abolished by propofol but propofol did not abolish morphine-induced delay of gastric emptying. Propofol in a low dose infusion reduced the incidence of PONV but nausea and especially vomiting increased significantly after termination of the infusion. Pro- phylaxis with the multidrug regimen was very effective in preventing PONV. These studies have shown that propofol does not have any dopamine antagonistic effect but may have a weak serotonin antagonistic effect. Propofol cannot abolish morphine-induced delay of gastric emptying. Low dose propofol infusion was effective in preventing PONV as long as the infusion was ongoing but after termination of the infusion nausea and especially vomiting substantially increased. The multidrug regimen (dexamethasone, ondansetron, droperidol, metoclopramide) was very effective in preventing PONV and can be recommended as prophylaxis in patient groups with a known high risk for PONV.

This thesis presents studies relating to the role of the gastrointestinal tract in postprandial blood pressure regulation. The areas that have been addressed include : ( i ) the methodological approaches to the evaluation of gastric emptying, blood pressure, splanchnic blood flow, intraluminal manometry and gut hormones and ( ii ) the pathophysiological mechanisms underlying postprandial hypotension, with a particular focus on ' gastric ' and ' small intestinal ' mechanisms and their potential therapeutic relevance. All of the studies have been either published or manuscripts have been prepared for publication. While scintigraphy represents the ' gold standard ' for the measurement of gastric emptying, recent studies suggest that three - dimensional ( 3D ) ultrasonography may also allow a precise measure of gastric emptying. Concurrent scintigraphic and ultrasonographic measurements of gastric emptying of liquids were performed in healthy young volunteers. There was a good correlation and agreement between scintigraphic measurements of gastric emptying and 3D ultrasonography after ingestion of both low - and high - nutrient drinks, indicating that 3D ultrasonography, provides a valid measure of gastric emptying of liquid meals in normal subjects. Postprandial hypotension, defined as a fall in systolic blood pressure of ≥ 20mmHg,occurring within two hours of a meal is now recognised as an important clinical problem, particularly in the elderly and in patients with type 2 diabetes. The mechanisms mediating postprandial hypotension are poorly understood. The effects of variations in concentration of intraduodenal glucose on the magnitude of the fall in blood pressure were evaluated in healthy elderly subjects. Blood pressure fell, and heart rate and blood glucose increased over time during infusions, however, there was no difference in blood pressure, heart rate or blood glucose concentrations between the study days. These observations suggest that glucose induced postprandial hypotension is a load rather, than concentration, dependent phenomenon. The effect of meal composition has been reported to influence the hypotensive response to a meal and information relating to the effects of triglyceride and protein on blood pressure is inconsistent. The comparative effects of isocaloric and isovolaemic intraduodenal infusions of glucose, triglyceride and protein on the magnitude of the postprandial fall in blood pressure and rise in heart rate and superior mesenteric artery blood flow were evaluated in healthy elderly subjects. There were comparable falls in systolic blood pressure and rises in heart rate, however, the maximum fall in systolic blood pressure occurred later after triglyceride and protein and the stimulation of superior mesenteric artery blood flow was less after protein. These observations suggest that the relatively slower systolic blood pressure response after triglyceride and protein may potentially reflect the time taken for digestion of triglyceride to free fatty acids and protein to amino acids. Acarbose is an antidiabetic drug that slows both gastric emptying and small intestinal glucose absorption. The effects of acarbose, on blood pressure, heart rate, gastric emptying of, and the glycaemic, insulin, glucagon - like peptide - 1 ( GLP - 1 ) and glucosedependent insulinotropic - polypeptide ( GIP ) responses to, an oral sucrose load were evaluated in healthy elderly subjects. Acarbose attenuated the fall in blood pressure and increase in heart rate induced by oral sucrose. Acarbose slowed gastric emptying and was associated with increased retention in the distal stomach. Stimulation of GLP - 1 may contribute to the slowing of gastric emptying and suppression of postprandial glycaemia by acarbose. These findings suggest that acarbose may represent a therapeutic option for the treatment of patients with postprandial hypotension. Recent studies indicate that gastric distension attenuates the postprandial fall in blood pressure. The effects of gastric distension on blood pressure and heart rate during intraduodenal infusion of glucose at a constant load and concentration were evaluated in healthy elderly subjects. Intragastric administration of water markedly attenuated the falls in systolic and diastolic blood pressure induced by intraduodenal glucose. Heart rate increased, with and without gastric distension, in response to intraduodenal glucose infusion but not after intraduodenal saline infusion. This study suggests that gastric distension may potentially be used as a simple adjunctive treatment in the management of postprandial hypotension. Studies employing nitric oxide synthase blockers have established, in animals, that nitric oxide mechanisms are important in the regulation of splanchnic blood flow and, hence, may effect postprandial blood pressure. The role of the nitric oxide synthase inhibitor, NG - nitro - L - arginine - methyl - ester ( L - NAME ), on gastric emptying, postprandial blood pressure, plasma insulin concentration and incretin hormone ( ie GIP and GLP - 1 ) release, following an oral glucose load, were evaluated in healthy elderly subjects. L - NAME attenuated the postprandial fall in blood pressure and increase in heart rate but had no effect on gastric emptying of glucose. L - NAME attenuated the glucose - induced rise in plasma insulin but had no effect on the incretin ( GIP and GLP - 1 ) hormone response to oral glucose. The study indicates that the magnitude of the fall in blood pressure and increase in heart rate and stimulation of insulin secretion induced by oral glucose in healthy elderly subjects are mediated by nitric oxide mechanisms by an effect unrelated to changes in gastric emptying, or the secretion of GIP and GLP - 1. Studies utilising 5 - hydroxytryptamine ( 5 - HT ) infusions in animals have demonstrated regional variations in intestinal blood flow suggesting a role for 5 - HT in postprandial haemodynamic responses. The effects of the 5 - hydroxytryptamine 3 ( 5 - HT3 ) antagonist, granisetron, on the blood pressure, heart rate, antropyloroduodenal motility and glycaemic responses to intraduodenal glucose infusion were assessed in healthy elderly subjects. Granisetron had no effect on blood pressure, heart rate or antral and pyloric motor responses but modulated the duodenal motor response, to intraduodenal glucose. This study indicates that while the cardiovascular response to intraduodenal glucose does not appear to be influenced by the stimulation of 5 - HT3 receptors, this receptor may be involved in the modulation of the duodenal motor activity. / Thesis (Ph.D.)--School of Medicine, 2006.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 6 uppsatser.