Cerebral perfusion is optimized during hemodilution by both β1- and β2-adrenergic mechanisms. Antagonism of the β2-adrenoreceptor can impair cerebral vasodilation. We hypothesized that treatment with a highly β1-specific antagonist (nebivolol) would minimize the degree of cerebral hypoxia during hemodilution. Anesthetized rats were randomized to receive vehicle or nebivolol (1.25 or 2.5 mg/kg intravenously) prior to hemodilution. In vehicle-treated rats, hemodilution increased cardiac output (CO) and regional cerebral blood flow (rCBF) while microvascular brain PO2 (PBrO2) decreased. Both nebivolol doses reduced heart rate and attenuated the CO response to hemodilution. Only the higher dose of nebivolol attenuated the rCBF response to hemodilution and caused a further reduction in PBrO2. Brain hypoxic protein levels were only increased in the high dose nebivolol group. High dose nebivolol treatment resulted in drug levels near its affinity for the β2-adrenoreceptor supporting the hypothesis that cerebral perfusion is maintained by β2-dependent mechanisms during hemodilution.

Cerebral perfusion is optimized during hemodilution by both β1- and β2-adrenergic mechanisms. Antagonism of the β2-adrenoreceptor can impair cerebral vasodilation. We hypothesized that treatment with a highly β1-specific antagonist (nebivolol) would minimize the degree of cerebral hypoxia during hemodilution. Anesthetized rats were randomized to receive vehicle or nebivolol (1.25 or 2.5 mg/kg intravenously) prior to hemodilution. In vehicle-treated rats, hemodilution increased cardiac output (CO) and regional cerebral blood flow (rCBF) while microvascular brain PO2 (PBrO2) decreased. Both nebivolol doses reduced heart rate and attenuated the CO response to hemodilution. Only the higher dose of nebivolol attenuated the rCBF response to hemodilution and caused a further reduction in PBrO2. Brain hypoxic protein levels were only increased in the high dose nebivolol group. High dose nebivolol treatment resulted in drug levels near its affinity for the β2-adrenoreceptor supporting the hypothesis that cerebral perfusion is maintained by β2-dependent mechanisms during hemodilution.

A apnéia central do sono (ACS) está associada à insuficiência cardíaca (IC). Objetivos: analisar o comportamento do sono em pacientes com IC e ACS com IAH>15 por hora e a influência dos betabloqueadores sobre o sono. Métodos: os pacientes realizaram duas polissonografias, com nitroglicerina e placebo, ambos transdérmicos. Resultados: em média, houve aumento da saturação de oxigênio e redução dos despertares e da frequência cardíaca, quando os pacientes fizeram uso de nitroglicerina. A prevalência de ACS no grupo betabloqueador foi menor do que relata a literatura. Conclusão: a nitroglicerina teve impacto positivo sobre variáveis polissonográficas. O betabloqueador reduziu a prevalência de apnéia. / The central sleep apnea (CSA) is associated to heart failure (HF). Objectives: Analyze sleeping behavior in patients with HF and CSA with AHI > 15 per hour, and the influence of beta-blocker on the sleep. Methods: patients were submitted to two sleep studies, with transdermic nitroglycerine and placebo. Results: On the average, we observed improvement in oxygen saturation and reduction in awakening episodes and in heart rate when patients slept with nitroglycerin compared to placebo. The prevalence of CSA in patients taking beta-blocker was inferior to that described in medical literature. Conclusion: Nitroglycerin had positive impact on sleep variables. Beta-blocker reduced CSA prevalence.

Heart failure is a syndrome in which the heart is unable to supply the entire body with oxygen. It is manifested in shortness of breath and exercise intolerance. One class of drugs that have proven effective in managing the progression of heart failure is β-blockers. These drugs bind to β-adrenergic receptors with high affinity, thus preventing the binding of endogenous catecholamines such as epinephrine and norepinephrine to the receptors by outcompeting them. The most common explanation of how β-blockers help manage the progression of heart failure is that by slowing the heart rate, it reduces the strain put on the heart. There may however be other ways that β-blockers help decrease morbidity and mortality of heart failure. Alternative reasons to how β-blockers aid the treatment of heart failure have been proposed based on the literature. It was found that the compensatory mechanisms intended to alleviate failure may be the main reasons that actually worsen it. Prolonged stimulation by epinephrine and norepinephrine damage the myocardium through oxidative damage, signaling for apoptosis and cardiac remodeling, as well as causing an increase in blood volume through the RAS-system. By blocking these maladaptive responses, β-blockers such as Carvedilol, Metoprolol and Nebivolol, together with other drugs such as ACE-inhibitors, and lifestyle changes help manage the progression of heart failure as well as increase the quality of life for the patients suffering from it

No description available.

An Herzinsuffizienz sind in Deutschland weit mehr als 1 Mio. Menschen erkrankt. Ihre Häufigkeit steigt stetig an. Die Herzinsuffizienz wird als dominierende Herz-Kreislauf-Erkrankung des 21. Jahrhunderts angesehen. Die Hauptursache der Herzinsuffizienz ist die koronare Herzerkrankung besonderes nach stattgehabtem Myokardinfarkt. Sowohl für den akuten Myokardinfarkt als auch für die sich auf dieser Basis entwickelnde Herzinsuffizienz werden Veränderungen im Stoffwechsel der Sauerstoffradikale als pathophysiologisch bedeutsam angesehen. Es wird angenommen, dass als Folge der akuten Myokardischämie oxidativer Stress im Myokard hervorgerufen wird. Dieser kann über die akute Infarktphase hinaus prolongieren. Dadurch werden Mechanismen induziert (Hypertrophie und Apoptose, Störung myokardialer Signaltransduktion), die letztlich zur Herzinsuffizienz führen. Folgerichtig sollten therapeutische Maßnahmen, die zu einer Minimierung von oxidativem Stress führen, protektiv wirken. Im Rahmen dieser Arbeit wurde am Modell des Ligaturinfarktes der Ratte gezeigt, dass es in der Akutphase des Infarktes (30-36 h nach Ligatur) zu gesteigertem oxidativen Stress kommt. Dieser ließ sich anhand gesteigerter myokardialer Konzentration an Lipidperoxiden, die mit einer verminderten Konzentration antioxidativer Enzyme im Herz kombiniert war, dokumentieren. Werden solche Tiere 6 Wochen nach Ligatur untersucht, weisen sie im Herz im Vergleich zu scheinoperierten Tieren eine signifikant erhöhte Konzentration von Lipidperoxiden als Zeichen gesteigerten oxidativen Stresses auf. Parallel dazu werden typische Zeichen einer Herzinsuffizienz (Herzhypertrophie, erhöhter LVEDP, verminderte Kontraktilität) beobachtet. Wurden solche Tiere beginnend nach der akuten Myokardphase mit dem ACE-Hemmer Ramipril und dem Beta-Blocker Metoprolol behandelt - von beiden ist bekannt, dass sie protektiv in den Stoffwechsel der Sauerstoffradikale eingreifen können - wurde ein geringerer myokardialer oxidativer Stress beobachtet, der mit einer verminderten Ausprägung der morphologischen und funktionellen Herzinsuffizienzzeichen einherging. Die kombinierte Gabe von Beta-Blocker und ACE-Hemmer erwies sich dabei sowohl in der Reduktion von oxidativem Stress als auch in ihrem Einfluss auf Herzfunktion und Morphologie den Einzeltherapien überlegen. Als wesentlich für die Reduktion von oxidativem Stress durch Beta-Blockade und ACE-Hemmung wurde die kompensatorische Zunahme des enzymatischen antioxidativen Schutzes im Herz (GSH-Px, SOD) ausgewiesen. / In Germany, more than 1 million people suffer from heart failure and the incidence is continuously growing. Consequently, heart failure is accepted to be the dominant disease of the heart and circulatory system in the 21st century. The main reason for heart failure is coronary heart disease in general, and especially myocardial infarction (MI). Changes in the oxygen radical metabolism are thought to be essential in the pathogenesis of myocardial infarction and heart failure as its important consequence. It is supposed that, as a result of myocardial ischemia, oxidative stress arises in the heart, which can activate and prolong mechanisms (hypertrophy, apoptosis, disturbed signal transduction) well documented to result in heart failure. Consequently, treatment, which reduces the myocardial oxidative stress, should be beneficial. Using the model of ligature infarction in rats, our study shows increased myocardial oxidative stress in the acute phase of MI (30-36 h after ligature) documented by increased concentration of lipid peroxides (LPO) combined with reduced activity of the antioxidative enzymes. When the animals were analyzed 6 weeks after ligature in comparison to sham operated animals, increased oxidative stress and in parallel typical signs for heart failure (myocardial hypertrophy, increased LVEDP, reduced contractility) were observed. Treatment of the animals starting after acute myocardial infarction with the ACE-inhibitor Ramipril and the beta-blocker Metoprolol - both are known to interfere protectively with the oxygen radical metabolism - reduced the myocardial oxidative stress and the morphological and functional signs of failing heart. This effect was most impressive after combined treatment with Metoprolol and Ramipril. The elevated enzymatic antioxidative defense (GSH-Px, SOD) which we found in the heart after beta-blockade and ACE inhibition could be the reason.

No description available.

Background: Surgical stress during resection surgery for colon cancer has previously been shown to be associated with adverse postoperative outcomes. Statin and beta-blocker treatment have been shown to lower postoperative complications and mortality, and been hypothesized to reduce the surgical stress response, although this correlation has not been studied clinically. Aim: To investigate whether perioperative beta-blocker and/or statin treatment reduce the postoperative C-reactive protein (CRP) response. Material and methods: All patients who underwent right sided hemicolectomy or sigmoid resection for cancer at Örebro University Hospital during 2012-2017 were included in this study. Initially, any treatment with statins, beta-blockers or both were compared to those with no treatment. After initial analyses, four treatment groups were compared regarding postoperative CRP response, namely no treatment, statin, beta-blocker, and combination treatment. Comparisons regarding complications were also performed for the four groups. Results: A total of 260 patients were included in this study. The no treatment group had a lower peak postoperative CRP than the treatment group, when comparing any treatment versus no treatment. There were no significant differences in postoperative CRP within the four treatment groups. There was no significant difference in complication rate between any of the treatment groups when compared to no treatment. Conclusion: Treatment with statin or beta-blocker therapy does not reduce the postoperative CRP response. A combination of both treatments demonstrated a trend towards a reduction regarding postoperative CRP response compared with the two treatments individually assessed. Larger studies are needed to verify the results of this study.

A hipertensão arterial pulmonar (HAP) é caracterizada pelo aumento da resistência vascular pulmonar (RVP). Em decorrência, há elevação da pós-carga imposta ao ventrículo direito (VD) e hipertrofia. Assim, com aumento de consumo de O2 pelo miocárdio, é provável que o estresse oxidativo esteja participando do desenvolvimento e progressão desta doença. Sabe-se que o bloqueio beta-adrenérgico diminui a mortalidade de pacientes com insuficiência cardíaca à esquerda, porém pouquíssimas pesquisas referem sua utilização na insuficiência cardíaca à direita. O bucindolol é um beta-bloqueador que atua nos receptores β1, β2, α1 e com propriedade simpatolítica. O objetivo deste estudo foi testar a hipótese de que o tratamento com bucindolol poderia reduzir a hipertrofia do VD e melhorar a função sistólica e diastólica do miocárdio. Foram utilizados ratos Wistar machos pesando 130±10 gramas divididos em quatro grupos (n=7-10/grupo): monocrotalina sem bucindolol (MCT SEM BCD), monocrotalina bucindolol (MCT+BCD), controle sem bucindolol (CTR SEM BCD) e controle bucindolol (CTR+BCD). A HAP foi induzida por meio de uma dose única de monocrotalina (60 mg/Kg – i.p.). Após duas semanas, os animas foram tratados por sete dias com bucindolol (2 mg/Kg/dia – i.p.) ou veículo. No 22º dia após a administração da monocrotalina, os animais foram anestesiados (i.p.) com quetamina (90 mg/Kg) e xilazina (10 mg/Kg), submetidos à ecocardiografia, cateterismo da artéria femoral, cateterismo do VD e decapitados, com posterior coleta dos tecidos. Os resultados foram avaliados utilizando ANOVA de duas vias (Sigma Plot 12.0) seguida pelo 8 teste de Student-Newman-Keuls, com nível de significância P<0,05. Os resultados serão apresentados na versão completa desta dissertação. / Pulmonary arterial hypertension is a rapidly progressive disease with poor prognosis, characterized by increase in pulmonary vascular resistance. As a result, there is an elevation of afterload imposed to the right ventricle and hypertrophy. Thus, since there is a rise in myocardial oxygen consumption, it is probable that oxidative stress is contributing to the development and progression of this disease. It is known that beta-adrenergic blockade reduces mortality in patients with left ventricular heart failure, but limited studies relate their use in right ventricular heart failure. The bucindolol is a beta-blocker that acts on receptors β1, β2, α1 and presents sympatholytic property. The aim of this study was to test the hypothesis that treatment with bucindolol could reduce right ventricular hypertrophy and improve systolic and diastolic function of the myocardium. Male Wistar rats weighing 130±10 grams were divided into four groups (n=7-10/group): monocrotaline without bucindolol (MCT WITHOUT BCD), monocrotaline bucindolol (MCT+BCD), control without bucindolol (CTR WITHOUT BCD) and control bucindolol (CTR+BCD). Pulmonary arterial hypertension was induced by a single dose of monocrotaline (60 mg/Kg – i.p.). After two weeks, the animals were treated for seven days with bucindolol (2 mg/Kg/day – i.p.) or vehicle. Twenty-two days after administration of monocrotaline, the animals were anesthetized intraperitoneally with ketamine (90 mg/Kg) and xylazine (10 mg/Kg), underwent echocardiography, catheterization of the femoral artery and of the right ventricle, decapitation and subsequent collection of tissues (heart, lungs, liver and tibia). The results were analyzed using two-way ANOVA (Sigma Plot 12.0) followed by 10 Student-Newman-Keuls test, with P<0.05 of significance level. Results will be presented in the full version.

A hipertensão arterial pulmonar (HAP) é caracterizada pelo aumento da resistência vascular pulmonar (RVP). Em decorrência, há elevação da pós-carga imposta ao ventrículo direito (VD) e hipertrofia. Assim, com aumento de consumo de O2 pelo miocárdio, é provável que o estresse oxidativo esteja participando do desenvolvimento e progressão desta doença. Sabe-se que o bloqueio beta-adrenérgico diminui a mortalidade de pacientes com insuficiência cardíaca à esquerda, porém pouquíssimas pesquisas referem sua utilização na insuficiência cardíaca à direita. O bucindolol é um beta-bloqueador que atua nos receptores β1, β2, α1 e com propriedade simpatolítica. O objetivo deste estudo foi testar a hipótese de que o tratamento com bucindolol poderia reduzir a hipertrofia do VD e melhorar a função sistólica e diastólica do miocárdio. Foram utilizados ratos Wistar machos pesando 130±10 gramas divididos em quatro grupos (n=7-10/grupo): monocrotalina sem bucindolol (MCT SEM BCD), monocrotalina bucindolol (MCT+BCD), controle sem bucindolol (CTR SEM BCD) e controle bucindolol (CTR+BCD). A HAP foi induzida por meio de uma dose única de monocrotalina (60 mg/Kg – i.p.). Após duas semanas, os animas foram tratados por sete dias com bucindolol (2 mg/Kg/dia – i.p.) ou veículo. No 22º dia após a administração da monocrotalina, os animais foram anestesiados (i.p.) com quetamina (90 mg/Kg) e xilazina (10 mg/Kg), submetidos à ecocardiografia, cateterismo da artéria femoral, cateterismo do VD e decapitados, com posterior coleta dos tecidos. Os resultados foram avaliados utilizando ANOVA de duas vias (Sigma Plot 12.0) seguida pelo 8 teste de Student-Newman-Keuls, com nível de significância P<0,05. Os resultados serão apresentados na versão completa desta dissertação. / Pulmonary arterial hypertension is a rapidly progressive disease with poor prognosis, characterized by increase in pulmonary vascular resistance. As a result, there is an elevation of afterload imposed to the right ventricle and hypertrophy. Thus, since there is a rise in myocardial oxygen consumption, it is probable that oxidative stress is contributing to the development and progression of this disease. It is known that beta-adrenergic blockade reduces mortality in patients with left ventricular heart failure, but limited studies relate their use in right ventricular heart failure. The bucindolol is a beta-blocker that acts on receptors β1, β2, α1 and presents sympatholytic property. The aim of this study was to test the hypothesis that treatment with bucindolol could reduce right ventricular hypertrophy and improve systolic and diastolic function of the myocardium. Male Wistar rats weighing 130±10 grams were divided into four groups (n=7-10/group): monocrotaline without bucindolol (MCT WITHOUT BCD), monocrotaline bucindolol (MCT+BCD), control without bucindolol (CTR WITHOUT BCD) and control bucindolol (CTR+BCD). Pulmonary arterial hypertension was induced by a single dose of monocrotaline (60 mg/Kg – i.p.). After two weeks, the animals were treated for seven days with bucindolol (2 mg/Kg/day – i.p.) or vehicle. Twenty-two days after administration of monocrotaline, the animals were anesthetized intraperitoneally with ketamine (90 mg/Kg) and xylazine (10 mg/Kg), underwent echocardiography, catheterization of the femoral artery and of the right ventricle, decapitation and subsequent collection of tissues (heart, lungs, liver and tibia). The results were analyzed using two-way ANOVA (Sigma Plot 12.0) followed by 10 Student-Newman-Keuls test, with P<0.05 of significance level. Results will be presented in the full version.