A descriptive study was conducted comparing the blood pressure and heart rate responses to position change among hypovolemic and normovolemic subjects. A convenience sample of 32 men and women from an emergency room with complaints of diarrhea, vomiting, vaginal or rectal bleeding for $\ge$12 hours duration were recruited. The normovolemic group consisted of a convenience sample of 30 men and women from the community. Data analysis included a mixed design analysis of variance. Compared to supine baseline measurements, between group changes in the systolic, diastolic, and mean arterial blood pressure were not statistically significant (p $>$.05). Once the subject stood, heart rate increased statistically significant in both groups (p $<$.05). The data suggest orthostatic hypotension can be considered when the supine resting heart rate is $\ge$87 beats per minute, and if upon standing, heart rate increases by $\ge$19.33 or is $\ge$110 beats per minute. Heart rate measurements should be taken at one minute after standing.

L'apéline est le ligand endogène du récepteur APJ, un membre de la superfamille des récepteurs couplés aux protéines G. Le système apélinergique est apparu comme une cible prometteuse associée à plusieurs processus physiologiques. Notre intérêt s'est porté particulièrement sur les rôles liés au système cardiovasculaire et à la modulation de la douleur. Nous posons l'hypothèse que la synthèse d'analogues de l'apéline-13 nous permettrait d'identifier d'une part des composés plus stables et d'autre part les voies de signalisation impliquées dans la modulation de la douleur, les effets hypotenseurs et cardioprotecteurs de notre cible. Ces outils pharmacologiques contribueront ultimement à concevoir un agent thérapeutique pour le traitement de la douleur chronique et des maladies cardiovasculaires. Les données de relations structure-fonction de l'apéline-13 révèlent la présence de deux pharmacophores distants importants. Le fragment N-terminal Arg[indice supérieur 2]-Pro[indice supérieur 3]-Arg[indice supérieur 4]-Leu[indice supérieur 5] semble primordial pour l'affinité, alors que la Phe[indice supérieur 13] C-terminale serait cruciale pour l'internalisation du récepteur et les effets hypotenseurs. Afin de mieux comprendre les relations structure-fonction de l'apéline-13, nous avons synthétisé près d'une centaine d'analogues linéaires et macrocycliques. Les composés ont été évalués pour leurs capacités à lier APJ, à inhiber la formation d'AMPc, à recruter les β-arrestines et à activer les protéines Gα[indice inférieur i/o]. Une variété de modifications chimiques a été introduite en C-terminal, nous conduisant à la découverte de composés de haute affinité et puissance. Deux analogues, 1Nal[indice supérieur 13] et 2Nal[indice supérieur 13], se sont distingués pour leurs différences d'effets analgésiques dans un modèle in vivo de douleur tonique. Ces derniers présentent une intéressante divergence de sélectivité fonctionnelle suggérant que l'effet analgésique serait associé à un biais favorisant le recrutement des β-arrestines par rapport à l'inhibition de l'accumulation d'AMPc. Un autre volet du projet dédié à l'investigation de la stabilité plasmatique de l'apéline-13 nous a permis d'identifier son profil de dégradation protéolytique in vitro et in vivo. L'évaluation des demi-vies plasmatiques des analogues de l'apéline-13, modifiés à des positions clés, a révélé l'importance de l'acide aminé C-terminal dans la stabilité plasmatique. Enfin, une étude préliminaire de SAR par une approche macrocyclique novatrice du ligand endogène nous a conduit à un composé induisant un effet hypotenseur deux fois supérieur à celui de l'apéline-13. Un autre macrocycle a, quant à lui, démontré une sélectivité fonctionnelle inédite, n'activant pas la voie AMPc mais provoquant le recrutement de la β-arrestine2. Cette classe de molécules, potentiellement plus stables, a un grand potentiel pour nous aider à identifier les voies de signalisation liées aux effets physiologiques d'intérêts, et représente surtout un premier pas vers un futur agent thérapeutique.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Orientador: Daniela Ponce / Coorientador: André Luis Balbi / Banca: Paqual Barreti / Banca: Eliane Maria Vasconcellos de Macedo / Resumo: A Hemodiálise Prolongada (HDP) é opção de suporte renal para pacientes críticos com lesão renal aguda (LRA) e instabilidade hemodinâmica. O tempo de HDP pode variar de 6 a 18h e as intercorrências mais comuns são hipotensão e coagulação de sistema. Este foi um estudo prospectivo do tipo ensaio clínico com objetivo de avaliar e comparar as intercorrências dialíticas ocorridas durante diferentes durações de HDP (sessões de 6 e 10h) em pacientes críticos com LRA. Foram incluídos pacientes maiores de 18 anos com LRA associada à sepse, internados em Unidade de Terapia Intensiva, em uso de noradrenalina na dose de 0,3 a 0,7 ug/kg/min. Os pacientes foram alocados em dois grupos de modo aleatório, o grupo 1 (G1) foi submetido a sessões de 6 h e o grupo 2 (G2) a sessões de 10h. Para análise dos dados foi utilizado o programa SAS for Windows, versão 9.2. As comparações das variáveis contínuas entre os grupos foram realizadas através do teste t Student e teste de Mann-Whitney, e para as variáveis categóricas, os testes do Qui-Quadrado e teste exato de Fisher. Para as comparações das variáveis por sessões foi utilizado o modelo misto de análise de medidas repetidas no tempo com ajuste para Tukey. Foi considerado o nível de significância de 5%. Setenta e cinco pacientes foram tratados com 195 sessões de HPD durante 18 meses consecutivos. A idade média foi de 61,8±15,1 anos, predomínio de sexo masculino (70,6%), o principal foco infeccioso foi abdominal (42,6%) e o Sequential Organ Failure Assessment (SOFA) 13,6±2,7. A prevalência de hipotensão, coagulação de sistema, hipofosfatemia e hipocalemia foi de 82,6, 25,3, 20 e 10,6%, respectivamente. O G1 foi composto de 38 pacientes tratados por 100 sessões, enquanto o G2 foi composto de 37 pacientes tratados por 95 sessões. Ao se comparar as características clínicas e laboratoriais, os grupos apresentaram-se semelhantes quanto à predominância do sexo ... / Abstract: Extended daily dialysis (EDD) has emerged as an alternative to CRRT in the management of hemodynamically unstable AKI patients, mainly in developed countries. This trial aimed to evaluate and compare the dialytics complications occurred during different durations of EDD sessions (6 vs.10h) in critically ill AKI patients. We included patients older than 18 years with AKI associated with sepsis admitted to the intensive care unit in use of norepinephrine dose ranged from 0.3 to 0.7 ucg/kg/min. Patients were divided into two groups randomly, group 1 (G1) was performed to sessions of 6 h and group 2 (G2) of 10h. Seventy - five patients were treated with 195 sessions EDD for 18 consecutive months. Age was 61.8 ± 15.1 years, predominantly male (70.6 %), the main focus of infection was abdominal (42.6 %) and SOFA was 13.6 ± 2.7. The prevalence of hypotension, filter clotting, hypokalemia, and hypophosphatemia was 82.6, 25.3, 20 and 10.6%, respectively. The G1 was composed of 38 patients treated with 100 sessions, whereas G2 consisted of 37 patients treated with 95 sessions. The two groups were similar in male predominance (65.7 vs. 75.6%, p = 0.34), age (63.614 vs. 59.915.5, p=0.28), and SOFA (13.12.4 vs. 14.23.0, p=0.2). There was no significant difference between the two groups in the prevalence of hypotension, filter clotting (81.5 vs. 83.7%, p=0.8 e 23.6 vs. 27%, p=0.73; respectively), hypokalemia and hypophosphatemia (13.1 vs. 8.1%, p=0.71 and 18.4 vs. 21.6%, p=0.72; respectively). However, the ... / Mestre

<div><b>Background:</b> Bradycardia and hypotension are complications commonly occurring during general anesthesia in small animals. Intraoperative hypotension has been found to be associated with adverse postoperative consequences. </div><div><br></div><div><b>Objectives: </b>The objectives of his study were first, to determine the incidence of bradycardia, hypotension, and bradycardia with hypotension in dogs undergoing general anesthesia, and second, to identify the risk factors associated with these three complications. The third objective was to evaluate the relationship between these three intraoperative complications and the recovery quality in these dogs.</div><div><br></div><div><b>Methods and Materials:</b> A retrospective cohort study was performed using anesthetic records from 250 dogs undergoing general anesthesia between May 23, 2018 and October 1, 2018 at the Purdue University Veterinary Teaching Hospital. Intraoperative bradycardia was defined as heart rate < 60 beats/min for at least two consecutive readings at 5 minutes apart. Hypotension was defined as mean arterial pressure (MAP) < 60 mmHg or a systolic arterial pressure (SAP) < 80 mmHg for at least two consecutive readings. A univariate analysis followed by multiple logistic regression was performed to build the model for bradycardia, hypotension, and bradycardia with hypotension. The relationships between the three complications and the recovery quality were analyzed using the Pearson’s chi-square test.</div><div><br></div><div><b>Results:</b> The study found that out of the 250 dogs, 114 (45.6%) developed bradycardia, 113 (45.2%) developed hypotension, and 32 (12.8%) dogs developed bradycardia with hypotension. The use of dexmedetomidine-based tranquilizers/sedatives, longer duration of anesthesia, and subjection to orthopedic and neurologic surgical procedures were all identified as risk factors for the dogs to develop bradycardia. The use of acepromazine-based tranquilizers/sedatives, young and old age dogs, and dogs subjected to neurologic surgery were associated with the development of intraoperative hypotension. When the length of the anesthesia increased, the chance for developing bradycardia with hypotension increased. There was no significant association between these intraoperative complications and the recovery quality.</div><div><b><br></b></div><div><b>Conclusions:</b> We found a high incidence of bradycardia or hypotension while a much lower incidence of bradycardia with hypotension in the anesthetized dogs. The risk factors for bradycardia were the use of dexmedetomidine-based tranquilizers/sedatives, the longer duration of anesthesia, and the performance of orthopedic surgery and neurosurgery. The risk factors for hypotension included the use of acepromazine-based tranquilizers/sedatives, the older or younger age of dogs, and the performance of neurosurgery. The risk factor for bradycardia with hypotension was the longer duration of anesthesia. While these adverse events developed intraoperatively, we could not identify a direct influence of these complications on the recovery quality. </div><div><br></div>

Pre-hypertension (pre-HT) (Blood Pressure (BP) ≥120/80mmHg to ≤ 140/90mmHg) increases the risk of developing hypertension (HT). BP reductions following acute exercise are known as post exercise hypotension (PEH). BP and perhaps PEH shows a daily circadian rhythm. Purpose: To compare the magnitude of PEH after morning and evening aerobic exercise in adults with pre-HT. Hypothesis: The magnitude of PEH will be larger after evening versus morning exercise. Participants: Pre-HT men and women 50-65 years old. Study Design: Participants engaged in cycling exercise (60% VO2max) on two occasions: 1.5 and 11 hours following waking. Cardiovascular function was assessed for 30 minutes pre and one hour post exercise. Results: 1) Systolic PEH responses affected by TOD differed by gender. 2) Baseline Heart Rate Variability and its response to exercise differed gender but not TOD. The inconsistent significant gender and TOD differences of PEH and its mechanisms suggest that this group.

Aerobic exercise is recommended as a lifestyle intervention to reduce blood pressure (BP) in individuals with elevated BP (SBP/DBP >120/80 mmHg). However, the BP response is highly variable after both acute (SBP/DBP: –27 to 9/-8 to 7mmHg) and chronic aerobic exercise (-20 to 9/ -11 to 11.3mmHg). We attempt to identify those who are resistant or responsive to training based on their responses to acute (one-bout) exercise. 17 prehypertensive (120 to 139/80 to 89mmHg) males and females (45-60yrs) underwent acute exercise assessments before and after an 8-week walking/jogging program. The magnitude of change in BP after acute exercise significantly correlated (r=.89, p < .01) with the magnitude of change in resting BP after the training. The antihypertensive mechanisms (total peripheral resistance, baroreflex sensitivity) for acute exercise were not correlated to those for chronic exercise. Central cardiovascular controls may link BP reductions after both acute and chronic exercise.

Aerobic exercise such as cycling is known to elicit a post-exercise hypotensive (PEH) response. However, it is not known if swim exercise produces a similar effect in normotensive individuals. We tested the hypothesis that an acute bout of swimming would elicit a PEH response that is less compared to an equivalent bout of cycling. 10 trained and 11 untrained normotensive (SBP/DBP < 120/80 mmHg) individuals (23±1 years) underwent 30 min intensity-matched cycling and swimming sessions to assess changes in BP and cardiovascular responses. While PEH was similar between modalities within groups, the magnitude and temporality of change in BP following swimming was significantly different (p < 0.01) between groups, with untrained participants showing a significant PEH response. Attenuation of PEH in trained individuals was reflective of a significant increase in sympathetic outflow and slower vagal reactivation, suggesting training in an aquatic environment leads to alterations in post-exercise BP regulatory mechanisms.

Pre-hypertension (pre-HT) (Blood Pressure (BP) ≥120/80mmHg to ≤ 140/90mmHg) increases the risk of developing hypertension (HT). BP reductions following acute exercise are known as post exercise hypotension (PEH). BP and perhaps PEH shows a daily circadian rhythm. Purpose: To compare the magnitude of PEH after morning and evening aerobic exercise in adults with pre-HT. Hypothesis: The magnitude of PEH will be larger after evening versus morning exercise. Participants: Pre-HT men and women 50-65 years old. Study Design: Participants engaged in cycling exercise (60% VO2max) on two occasions: 1.5 and 11 hours following waking. Cardiovascular function was assessed for 30 minutes pre and one hour post exercise. Results: 1) Systolic PEH responses affected by TOD differed by gender. 2) Baseline Heart Rate Variability and its response to exercise differed gender but not TOD. The inconsistent significant gender and TOD differences of PEH and its mechanisms suggest that this group.

Aerobic exercise is recommended as a lifestyle intervention to reduce blood pressure (BP) in individuals with elevated BP (SBP/DBP >120/80 mmHg). However, the BP response is highly variable after both acute (SBP/DBP: –27 to 9/-8 to 7mmHg) and chronic aerobic exercise (-20 to 9/ -11 to 11.3mmHg). We attempt to identify those who are resistant or responsive to training based on their responses to acute (one-bout) exercise. 17 prehypertensive (120 to 139/80 to 89mmHg) males and females (45-60yrs) underwent acute exercise assessments before and after an 8-week walking/jogging program. The magnitude of change in BP after acute exercise significantly correlated (r=.89, p < .01) with the magnitude of change in resting BP after the training. The antihypertensive mechanisms (total peripheral resistance, baroreflex sensitivity) for acute exercise were not correlated to those for chronic exercise. Central cardiovascular controls may link BP reductions after both acute and chronic exercise.