RESUMO
BACKGROUND: Respiratory responses to extubation can cause serious postoperative complications. Beta-blockers, such as metoprolol, can interfere with the cough pathway. However, whether metoprolol can effectively control respiratory reflexes during extubation remains unclear. The objective of this study is to evaluate the efficacy of intravenous metoprolol in attenuating respiratory responses to tracheal extubation. METHODS: Randomized, double-blinded, placebo-controlled trial. SETTING: Tertiary referral center located in Brasília, Brazil. Recruitment: June 2021 to December 2021. SAMPLE: 222 patients of both sexes with an American Society of Anesthesiologists (ASA) physical status I-III aged 18-80 years. Patients were randomly assigned to receive intravenous metoprolol 5 mg IV or placebo at the end of surgery. The primary outcome was the proportion of patients who developed bucking secondary to endotracheal tube stimulation of the tracheal mucosa during extubation. Secondary outcomes included coughing, bronchospasm, laryngospasm, Mean Blood Pressure (MAP), and Heart Rate (HR) levels. RESULTS: Two hundred and seven participants were included in the final analysis: 102 in the metoprolol group and 105 in the placebo group. Patients who received metoprolol had a significantly lower risk of bucking (43.1% vs. 64.8%, Relative Risk [RR = 0.66], 95% Confidence Interval [95% CI 0.51-0.87], p = 0.003). In the metoprolol group, 6 (5.9%) patients had moderate/severe coughing compared with 33 (31.4%) in the placebo group (RR = 0.19; 95% CI 0.08-0.43, p < 0.001). CONCLUSION: Metoprolol reduced the risk of bucking at extubation in patients undergoing general anesthesia compared to placebo.
Assuntos
Extubação , Metoprolol , Masculino , Feminino , Humanos , Metoprolol/uso terapêutico , Metoprolol/farmacologia , Frequência Cardíaca , Pressão Arterial , Intubação Intratraqueal/efeitos adversos , Método Duplo-CegoRESUMO
6-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective ß-adrenergic receptor antagonists has been associated with ejaculatory failure. Here, the effects of selective ß1- and ß1/ß2-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline, and electric-field stimulation (EFS) were investigated. The selective ß1-adrenergic receptor antagonists atenolol (0.1 and 1 µï»¿M), betaxolol (1 µï»¿M), and metoprolol (1 µï»¿M) and the unselective ß1/ß2-adrenergic receptor antagonists propranolol (1 and 10 µï»¿M) and pindolol (10 µï»¿M) caused significant rightward shifts of the concentration-response curve to 6-ND (pA2 6.41, 6.91, 6.75, 6.47, and 5.74; for atenolol, betaxolol, metoprolol, propranolol, and pindolol), but had no effect on dopamine-, noradrenaline-, and adrenaline-induced contractions. The effects of selective ß1- and ß1/ß2-adrenergic receptor antagonists at a higher concentration (atenolol 1 µï»¿M, betaxolol 1 µï»¿M, metoprolol 1 µï»¿M, propranolol 10 µï»¿M, and pindolol 10 µï»¿M) also reduced the EFS-induced RIEVD contractions in control, but not in RIEVD obtained from L-NAME-treated animals. The selective ß1-adrenoceptor agonist RO-363, the selective ß2-adrenoceptor agonist salbutamol, and the selective ß3-adrenoceptor agonist mirabegron, up to 300 µï»¿M, had no effect on the RIEVD tone. The results demonstrate that ß1- and ß1-/ß2-adrenoceptor receptor antagonists act as 6-ND receptor antagonists in RIEVD, further confirming the main role of 6-ND in the RIEVD contractility.
Assuntos
Propranolol , Ducto Deferente , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Antagonistas de Receptores Adrenérgicos beta 2/farmacologia , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Atenolol/farmacologia , Betaxolol/farmacologia , Dopamina/análogos & derivados , Epinefrina/farmacologia , Masculino , Metoprolol/farmacologia , Norepinefrina/farmacologia , Pindolol/farmacologia , Propranolol/farmacologia , RatosRESUMO
OBJECTIVE: To evaluate the ability of heart rate (HR) and HR difference during head-up tilt test (HUTT) and to predict clinical improvement related to metoprolol treatment in children and adolescents with postural tachycardia syndrome (POTS). STUDY DESIGN: This was a retrospective cohort study. A total of 53 subjects (27 male, aged 6-12 years old, mean age 11.79 ± 1.50 years old) with POTS treated with metoprolol were involved from July 2012 to September 2019. In total, 52 subjects who underwent health examination during the same period were matched as the control group. Subjects in both groups underwent HUTT. The HR distance between 5 minutes and 0 minutes (HR difference 5) and between 10 minutes and 0 minutes (HR difference 10) during HUTT was calculated. RESULTS: The POTS group was significantly greater than the control group in HR 5, HR 10, HR difference 5, and HR difference 10 (P < .01). There was no statistical difference in HR 0 between the 2 groups (P > .05). In total, 53 subjects with POTS were followed up for 96.0 (IQR, 40.5, 134.5) days during treatment with metoprolol. HUTT results demonstrated that 58.49% of subjects with POTS had a response and symptom scores were reduced after intervention. HR and HR difference were useful in predicting the efficacy of metoprolol on POTS. When HR 5, HR 10, HR difference 5, and HR difference 10, respectively, were ≥110, 112, 34, and 37 beats/min, the sensitivity and specificity were 82.50% and 69.23%, 84.62% and 69.70%, 85.29% and 89.47%, and 97.56% and 64.86%, respectively. CONCLUSIONS: HR and HR difference are helpful to predict the efficacy of metoprolol on POTS in children and adolescents.
Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Metoprolol/farmacologia , Síndrome da Taquicardia Postural Ortostática/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Metoprolol/uso terapêutico , Síndrome da Taquicardia Postural Ortostática/fisiopatologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Posição OrtostáticaRESUMO
AIM: To examine the interference of ß-blockers with the chemokine stromal cell-derived factor-1 (SDF-1) found in cell homing receptors, C-X-C chemokine receptor type 4 (CXCR-4) and CXCR-7, and regulatory proteins of homing pathways, we administered atenolol, carvedilol, metoprolol, and propranolol for 30 days using an orogastric tube to hypertensive rats. METHOD: We collected blood samples before and after treatment and quantified the levels of SDF-1 with enzyme-linked immunosorbent assay (ELISA). On day 30 of treatment, the spontaneously hypertensive rats (SHR) were euthanized, and heart, liver, lung, and kidney tissues were biopsied. Proteins were isolated for determining the expression of CXCR-4, CXCR-7, GRK-2 (G protein-coupled receptors kinase 2), ß-arrestins (ß1-AR and ß2-AR), and nuclear factor kappa B (NFκB). RESULTS: We found that the study drugs modulated these proteins, and metoprolol and propranolol strongly affected the expression of ß1-AR (P = .0102) and ß2-AR (P = .0034). CONCLUSION: ß-blockers modulated tissue expression of the proteins and their interactions following 30 days of treatment. It evidences that this class of drugs can interfere with proteins of cell homing pathways.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anti-Hipertensivos/farmacologia , Movimento Celular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Atenolol/farmacologia , Carbazóis/farmacologia , Carvedilol , Quimiocina CXCL12/sangue , Modelos Animais de Doenças , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Hipertensão/sangue , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Metoprolol/farmacologia , Miocárdio/metabolismo , NF-kappa B/metabolismo , Propanolaminas/farmacologia , Propranolol/farmacologia , Ratos Endogâmicos SHR , Receptores CXCR/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta-Arrestina 1/metabolismo , beta-Arrestina 2/metabolismoRESUMO
Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI) receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx) generating approximately 10% of injured LV area with minimum hemodynamic impact. We assessed tissue perfusion by real time myocardial perfusion echocardiography (RTMPE) using commercial microbubbles before and following pASCs treatment. Four weeks after the occlusion of the left circumflex artery, we transplanted placebo or pASCs (1, 2 and 4x106 cells/Kg BW) into the myocardium. The highest dose of pASCs increased myocardial vessel number and blood flow in the border (56% and 3.7-fold, respectively) and in the remote area (54% and 3.9-fold, respectively) while the non-perfused scar area decreased (up to 38%). We also found an increase of immature collagen fibers, although the increase in total tissue collagen and types I and III was similar in all groups. Our results provide evidence that pASCs-induced stimulation of tissue perfusion and accumulation of immature collagen fibers attenuates adverse remodeling post-MI beyond the normal beneficial effects associated with ACE inhibition and beta-blockade.
Assuntos
Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Remodelação Ventricular , Animais , Circulação Coronária/efeitos dos fármacos , Enalaprilato/farmacologia , Feminino , Hemodinâmica/efeitos dos fármacos , Metoprolol/farmacologia , Infarto do Miocárdio/fisiopatologia , Suínos , Transplante Homólogo , Remodelação Ventricular/efeitos dos fármacosRESUMO
BACKGROUND: It is known that epinephrine/norepinephrine inhibit acute pain transmission. However, the role of ß-adrenoceptors is not clear. Thus, we analyzed if beta-1 and/or beta-2 adrenoceptors can modulate acute pain transmission by performing in vivo single unit recordings during painful and non-painful peripheral stimulation in rats. METHODS: Longitudinal study in which we analyzed seven groups of male rats Wistar: control group (n = 11): saline (0.9 %); EPI group (n = 8): epinephrine 100 mcg; beta-1 agonist group (n = 8): dobutamine 125 mcg; beta-1-antagonist group (n = 9): metoprolol 100 mcg; beta-2-agonist group (n = 7): clenbuterol 100 mcg; beta-2-antagonist group (n = 8): butoxamine 100 mcg; beta-1-antagonist + EPI group (n = 10): metoprolol 100 mcg + epinephrine 100 mcg. For the statistical analysis we used ANOVA. RESULTS: Epinephrine significantly reduced the basal firing rate (BFR) in 34.1 % (p < 0.05) and also the evoked response by painful stimulation in 56 % (p < 0.05). No change was observed in the evoked response by non-painful stimulation. ANTß1 was the only beta-adrenoceptor acting drug that significantly reduced the evoked response by painful stimulation in 41 % (p < 0.05). None of the other drugs alone affected either the BFR or the evoked response to non-painful or painful stimulation. CONCLUSIONS: It is the first time that a beta-1-adrenoceptor antagonist (metoprolol) probes to be effective in reducing the response to painful stimulation in WDR neurons.
Introducción: la epinefrina/norepinefrina inhibe la transmisión del dolor agudo; empero, no es claro el papel de los receptores beta-adrenérgicos. Por tanto, analizamos si los fármacos de estos receptores modulan la transmisión del dolor agudo mediante registro electrofisiológico unitario extracelular in vivo durante estimulación periférica dolorosa y no dolorosa en ratas. Métodos: estudio longitudinal en el que se cotejaron siete grupos de ratas: control (n = 11): solución salina (0,9 %); EPI (n = 8): 100 mcg epinefrina; agonista beta-1 (n = 8): 125 mcg dobutamina; antagonista beta-1 (n = 9): 100 mcg metoprolol; agonista beta-2 (n = 7): 100 mcg clembuterol; antagonista beta-2 (n = 8): butoxamina 100 mcg; antagonista beta-1 + EPI (n = 10): 100 mcg metoprolol + 100 mcg epinefrina. Se hizo análisis estadístico por medio de ANOVA. Resultados: La epinefrina redujo significativamente la tasa de disparo basal (RDB) en 34.1 % (p < 0.05) y la respuesta evocada por la estimulación dolorosa en 56 % (p < 0.05). No hubo cambios en la respuesta provocada por la falta de estimulación dolorosa. El antagonista beta-1 fue el único fármaco con acción beta-adrenérgica que redujo significativamente la respuesta evocada por la estimulación dolorosa en 41 % (p < 0.05). Conclusión: por primera vez un antagonista de los receptores beta-1-adrenérgicos (metoprolol) prueba ser eficaz en la reducción de la respuesta a la estimulación dolorosa en las neuronas ARD.
Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Metoprolol/uso terapêutico , Dor/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Masculino , Metoprolol/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Estimulação Física , Ratos , Ratos Wistar , Medula EspinalRESUMO
RATIONALE: Sorafenib is an effective treatment for renal cell carcinoma, but recent clinical reports have documented its cardiotoxicity through an unknown mechanism. OBJECTIVE: Determining the mechanism of sorafenib-mediated cardiotoxicity. METHODS AND RESULTS: Mice treated with sorafenib or vehicle for 3 weeks underwent induced myocardial infarction (MI) after 1 week of treatment. Sorafenib markedly decreased 2-week survival relative to vehicle-treated controls, but echocardiography at 1 and 2 weeks post MI detected no differences in cardiac function. Sorafenib-treated hearts had significantly smaller diastolic and systolic volumes and reduced heart weights. High doses of sorafenib induced necrotic death of isolated myocytes in vitro, but lower doses did not induce myocyte death or affect inotropy. Histological analysis documented increased myocyte cross-sectional area despite smaller heart sizes after sorafenib treatment, further suggesting myocyte loss. Sorafenib caused apoptotic cell death of cardiac- and bone-derived c-kit+ stem cells in vitro and decreased the number of BrdU+ (5-bromo-2'-deoxyuridine+) myocytes detected at the infarct border zone in fixed tissues. Sorafenib had no effect on infarct size, fibrosis, or post-MI neovascularization. When sorafenib-treated animals received metoprolol treatment post MI, the sorafenib-induced increase in post-MI mortality was eliminated, cardiac function was improved, and myocyte loss was ameliorated. CONCLUSIONS: Sorafenib cardiotoxicity results from myocyte necrosis rather than from any direct effect on myocyte function. Surviving myocytes undergo pathological hypertrophy. Inhibition of c-kit+ stem cell proliferation by inducing apoptosis exacerbates damage by decreasing endogenous cardiac repair. In the setting of MI, which also causes large-scale cell loss, sorafenib cardiotoxicity dramatically increases mortality.
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Coração/efeitos dos fármacos , Infarto do Miocárdio/mortalidade , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/farmacologia , Animais , Apoptose/efeitos dos fármacos , Gatos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Técnicas In Vitro , Masculino , Metoprolol/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Niacinamida/efeitos adversos , Niacinamida/farmacologia , Proteínas Proto-Oncogênicas c-kit/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-kit/metabolismo , SorafenibeRESUMO
AIM: The present study was designed to investigate the effects of estradiol-ethylenediamine derivative on perfusion pressure and coronary resistance in rats. An additional aim was to identify the molecular mechanisms involved. METHODS: The Langendorff model was used to measure perfusion pressure and coronary resistance changes in isolated rat heart after estradiol-ethylenediamine derivative alone and following compounds; tamoxifen (estrogen receptor antagonist), prazosin (alpha1 adrenoreceptor antagonist), metoprolol (selective beta1 receptor blocker), indomethacin (prostanglandin synthesis inhibitor) and nifedipine (L-type calcium-channel inhibitor). RESULTS: The results show that estradiol-ethylenediamine derivative [10(-9) mmol] significantly increased perfusion pressure (p = 0.005) and coronary resistance (p = 0.006) in isolated rat heart. Additionally, the effect of estradiolethylenediamine on perfusion pressure [10(-9) to 10(-4) mmol] was only blocked in the presence of the L-type calcium-channel (nifedipine). CONCLUSIONS: These data suggest that the effect of estradiol-ethylenediamine on perfusion pressure and vascular coronary involves activation of the L-type calcium channel through a non-genomic molecular mechanism.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , Circulação Coronária/efeitos dos fármacos , Estradiol/análogos & derivados , Estradiol/farmacologia , Miocárdio/metabolismo , Resistência Vascular/efeitos dos fármacos , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Antagonistas de Estrogênios/farmacologia , Etilenodiaminas/farmacologia , Feminino , Técnicas In Vitro , Indometacina/farmacologia , Metoprolol/farmacologia , Nifedipino/farmacologia , Prazosina/farmacologia , Ratos , Ratos Wistar , Tamoxifeno/farmacologiaRESUMO
1. In the present study, we evaluated the autonomic balance of the heart in protein/energy-undernourished rats. 2. Rats were divided into two groups according to the diet they received after weaning: (i) the control group (n=16), given a 15% protein diet, and (ii) the malnourished group (n=14), fed a 6% protein diet. Cardiovascular recordings were made and, through selective autonomic blockade, the tonic autonomic balance, cardiac autonomic index and the power spectrum of heart rate (HR) variability were determined. 3. Muscarinic receptor blockade with methylatropine (5.0 mg/kg, i.v.) increased HR in the control group (371 ± 6 vs 427 ± 15 b.p.m. before and after drug administration, respectively), but not the malnourished group (438 ± 24 vs 472 ± 38 b.p.m. before and after drug administration, respectively). Inhibition of ß(1)-adrenoceptors with metoprolol (2.0 mg/kg, i.v.) reduced HR in malnourished rats (428 ± 24 vs 355 ± 16 b.p.m. before and after drug administration, respectively), but had no effect on the HR of the control group (363 ± 8 vs 362 ± 7 b.p.m. before and after drug administration, respectively). Double autonomic blockade by inhibiting both muscarinic cholinoceptors and ß(1)-adrenoceptors reduced HR in the malnourished group (428 ± 24 vs 342 ± 14 b.p.m.) but had no effect on HR in the control group (371 ± 6 vs 382 ± 6 b.p.m.). 4. Sympathetic tone was augmented in malnourished compared with control rats (131 ± 17 vs 41 ± 11 b.p.m., respectively), whereas parasympathetic tone was reduced in malnourished compared with control rats (-4 ± 4 vs 22 ± 9 b.p.m., respectively). 5. The ratio of oscillations in HR induced by sympathetic and parasympathetic activity was higher in malnourished compared with control rats (0.43 ± 0.03 vs 0.34 ± 0.02, respectively). 6. The results of the present study indicate that protein malnutrition after weaning increases sympathetic activity and reduces vagal activity to the heart in rats. These data provide a new perspective on the pathophysiology of metabolic and cardiovascular diseases associated with protein malnutrition, especially with regard to autonomic modulation.
Assuntos
Sistema Nervoso Autônomo/fisiologia , Doenças Cardiovasculares/fisiopatologia , Desnutrição Proteico-Calórica/fisiopatologia , Animais , Derivados da Atropina/administração & dosagem , Derivados da Atropina/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Dieta com Restrição de Proteínas , Eletrocardiografia , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Metoprolol/administração & dosagem , Metoprolol/farmacologia , Parassimpatolíticos/administração & dosagem , Parassimpatolíticos/farmacologia , Ratos , Ratos Endogâmicos F344 , Simpatolíticos/administração & dosagem , Simpatolíticos/farmacologia , DesmameRESUMO
FUNDAMENTO: O tratamento da insuficiência cardíaca (IC) conta atualmente com diversos tipos de intervenções. Dentre elas, destacam-se a terapia com betabloqueadores (BB) e o treinamento físico (TF). Contudo, os efeitos da associação dessas terapias são pouco estudados. OBJETIVO: Verificar os efeitos do tratamento com BB, metoprolol (M) e carvedilol (C) associados ao TF na IC em camundongos. MÉTODOS: Utilizamos modelo genético de IC induzida em camundongos por hiperatividade simpática. Inicialmente, dividimos os animais com IC em: sedentários (S); treinados (T); tratados com M (138 mg/kg) (M) ou C (65 mg/kg) (C). Na segunda parte, dividimos os grupos em S; treinado e tratado com M (MT) e treinado e tratado com C (CT). O TF consistiu em treinamento aeróbico em esteira por 8 semanas. A tolerância ao esforço foi avaliada por teste progressivo máximo e a fração de encurtamento foi avaliada (FE) por ecocardiografia. O diâmetro dos cardiomiócitos e a fração de colágeno foram avaliados por meio de análise histológica. Os dados foram comparados por ANOVA de um caminho com post hoc de Duncan. O nível de significância foi considerado p < 0,05. RESULTADOS: Destacando FE e remodelação cardíaca, verificamos que, isoladamente, T, M e C apresentaram melhora das variáveis. Na associação, após o período de intervenção, observamos aumento da tolerância ao esforço em MT e CT (43,0 por cento e 33,0 por cento, respectivamente). Houve também redução do diâmetro dos cardiomiócitos (10,0 por cento e 9,0 por cento, respectivamente) e da fração de colágeno (52,0 por cento e 63,0 por cento), após a intervenção. Porém, somente CT melhorou significantemente a FE. CONCLUSÃO: A associação do TF às terapias com M ou C proporcionou benefícios sobre a função e remodelação cardíaca em camundongos com IC.
BACKGROUND: Currently there are several types of interventions for the treatment of heart failure (HF). Among these are beta-blocker therapy (BB) and physical training (PT). However, the effects of the combination of these therapies are poorly studied. OBJECTIVE: To investigate the effects of BB treatment with metoprolol (M) and carvedilol (C) associated with PT in mice with HF. METHODS: We used a genetic model of sympathetic hyperactivity-induced heart failure in mice. Initially, we divided the HF animals into three groups: sedentary (S); trained (T); treated with M (138 mg/kg) (M); or C (65 mg/kg) (C). In the second part, we divided the groups into three subgroups: sedentary (S); trained and treated with M (TM); and trained and treated with C (CT). The PT consisted of aerobic training on a treadmill for 8 weeks. Exercise tolerance was assessed by maximal graded test, and fractional shortening (FS) was assessed by echocardiography. Cardiomyocyte diameter and collagen volume fraction were evaluated by histological analysis. Data were compared by one way ANOVA and post hoc Duncan test. The significance level was set at p < 0.05. RESULTS: As to FS and cardiac remodeling, we found that, in isolation, T, M, and C showed an improvement of the variables analyzed. As to therapy combination, after the intervention period, we observed an increase in exercise tolerance in MT and CT (43.0 percent and 33.0 percent respectively). There was also a reduction in cardiomyocyte diameter (10.0 percent and 9.0 percent respectively) and in collagen volume fraction (52.0 percent and 63.0 percent) after the intervention. However, only CT significantly improved FS. CONCLUSION: The association of PT with M or C therapies provided benefits on cardiac function and remodeling in HF mice.
FUNDAMENTO: El tratamiento de la insuficiencia cardiaca (IC) cuenta actualmente con diversos tipos de intervenciones. De entre ellas podemos destacar la terapia con betabloqueantes (BB) y el entrenamiento físico (EF). Con todo, los efectos de la asociación de estas terapias son poco estudiados. OBJETIVO: Verificar los efectos del tratamiento con BB, metoprolol (M) y carvedilol (C) asociados al EF en la IC en ratones. MÉTODOS: Utilizamos modelo genético de IC inducida en ratones por hiperactividad simpática. Inicialmente, dividimos los animales con IC en: sedentarios (S); entrenados (E); tratados con M (138 mg/kg) (M) o C (65 mg/kg) (C). En la segunda parte, dividimos los grupos en S; entrenado y tratado con M (ME) y entrenado y tratado con C (CE). El EF consistió en entrenamiento aeróbico en estera por 8 semanas. La tolerancia al esfuerzo se evaluó por prueba progresivo máxima y la fracción de acortamiento se evaluó (FE) por ecocardiografía. El diámetro de los cardiomiocitos y la fracción de colágeno fueron evaluados por medio de análisis histológico. Los dados fueron comparados por ANOVA de un camino con post hoc de Duncan. El nivel de significancia se consideró como p < 0,05. RESULTADOS: Destacando FE y remodelación cardíaca, verificamos que, aisladamente, E, M y C presentaron mejora de las variables. En la asociación, tras el período de intervención, observamos aumento de la tolerancia al esfuerzo en ME y CE (el 43 por ciento y el 33 por ciento, respectivamente). Hubo también reducción del diámetro de los cardiomiocitos (el 10 por ciento y el 9 por ciento, respectivamente) y de la fracción de colágeno (el 52 por ciento y el 63 por ciento), tras la intervención. Sin embargo, solamente CE mejoró significantemente la FE. CONCLUSIÓN: La asociación del EF a las terapias con M o C proporcionó beneficios sobre la función y remodelación cardíaca en ratones con IC.