Heart rate lowering agents in acute coronary syndrome

Background: Heart rate is a key indicator of cardiovascular mortality, with ACS having the highest mortality risk when heart rate is elevated. With a target heart rate of <70 bpm, it is crucial to evaluate the effects of medications that lowers heart rate. Methods: In this prospective observational study, 45 patients with ACS were studied, and it was determined whether or not the patients' heart rates at discharge from the hospital were within goal range. Additionally, we looked at demographics, drug-related issues, vitals and then statistical tests were performed. Results: The demographic of 45 patients showed mean adult age was 47 years and most observed ACS was STEMI (53.3%). Patients prescribed with HRLA showed lower mean HR, SBP and DBP at discharge. Evaluated Optimal HR ?70 bpm with HRLA therapy at discharge of the inpatients was achieved in 26.6% (63.5±5.5 bpm). Conclusions: The current study showed HRLA therapy effectively reduced the heart rate at hospital discharge, but despite being on HRLA only 1/4th of patients achieved the optimal heart rate.

Effect of preoperative oral bisoprolol on intraoperative outcomes in endoscopic sinus surgery

Background: Endoscopic sinus surgery (ESS) presents challenges in managing intraoperative bleeding and hemodynamic stability. This study evaluates the efficacy of pre-operative oral bisoprolol in improving surgical conditions and outcomes in ESS. Methods: This study was conducted between March 2021 and June 2022 at the department of anaesthesia, Bangabandhu Sheikh Mujib medical University, Dhaka, Bangladesh. This randomized controlled trial was conducted with 50 participants undergoing elective ESS, divided into bisoprolol and placebo groups. Result: The study involved 50 participants undergoing elective ESS, with 25 in the bisoprolol group and 25 in the placebo group. While demographic characteristics, such as age, weight, height, and gender distribution, showed no statistically significant differences between the groups. The placebo group experienced significantly higher estimated blood loss (421.72 ml vs. 156.24 ml, p<0.001) and postoperative hemoglobin levels (12.88 g/dl vs. 11.07 g/dl, p<0.001) compared to the bisoprolol group. Hemodynamic parameters, particularly heart rate, exhibited significant differences at various time points, with the bisoprolol group maintaining a higher heart rate post-premedication, intra-operatively, and post-operatively (p<0.05 for all). In the assessment of intraoperative bleeding using the Fromme-Boezaart scale, the placebo group demonstrated higher incidences of severe bleeding grades (3 and 4) compared to the bisoprolol group, with these differences being statistically significant (p<0.001). Conclusions: Pre-operative oral bisoprolol in ESS patients significantly reduces intraoperative bleeding and anesthetic requirements while maintaining hemodynamic stability. These findings suggest bisoprolol as a beneficial pre-operative medication in ESS, warranting further research to optimize surgical outcomes.

El papel de la Ivabradina y la titulación de los betabloqueadores en la insuficiencia cardíaca: una serie de casos y revisión de la literatura / The role of Ivabradine and beta-blocker titration in heart failure: a case series and literature review

RESUMEN Introducción y objetivos : La insuficiencia cardíaca (IC) es una preocupación creciente de salud pública. Si bien los betabloqueantes (BB) son la base del tratamiento, lograr reducciones objetivo de frecuencia cardíaca puede ser difícil debido a los efectos secundarios y la tolerancia limitada. La ivabradina, un inhibidor único de la corriente If, ofrece un enfoque complementario para controlar la frecuencia cardíaca sin afectar la contractilidad. El objetivo de este estudio fue evaluar la eficacia de agregar ivabradina a la terapia BB en pacientes con IC. Métodos: Se realizó un estudio observacional retrospectivo en un hospital privado en San José, Costa Rica se analizaron 7 casos de pacientes tratados con BB a los cuales posteriormente se les adicionó ivabradina. Se recopilaron datos demo- gráficos, las características clínicas, la frecuencia cardíaca previa y posterior a la ivabradina, la clase funcional NYHA y los valores de laboratorio seleccionados. Resultados: La ivabradina redujo significativamente la frecuencia cardíaca en reposo en un promedio de 26,87 latidos por minuto. El 42,86% alcanzó la dosis meta de su BB inicial después de agregar ivabradina. La clase funcional NYHA se mantuvo estable o mejoró en todos los casos. Conclusiones: Estos resultados sugieren que agregar ivabradina a la terapia BB puede ser una estrategia eficaz para optimizar el control de la frecuencia cardíaca en pacientes con IC. Este enfoque puede mejorar la tolerabilidad de BB, lo que lleva a un mayor manejo de la dosis meta y posiblemente mejores resultados clínicos.

ABSTRACT Introduction and objectives: Heart failure (HF) is a growing public health concern. While beta-blockers (BBs) are the cornerstone of treatment, achieving target heart rate reductions can be difficult due to side effects and limited tolerance. Ivabradine, a unique inhibitor of the If current, offers a complementary approach to controlling heart rate without affecting contractility. This study aimed to evaluate the effectiveness of adding ivabradine to BB therapy in patients with HF. Methods : A retrospective observational study was conducted at a private hospital in San José, Costa Rica. Seven cases of patients treated with BBs who were subsequently added to ivabradine were analyzed. Demographic data, clinical characteristics, heart rate before and after ivabradine, NYHA functional class, and selected laboratory values were collected. Results : Ivabradine significantly reduced resting heart rate by an average of 26.87 beats per minute. Forty-two-point eight-six percent (42.86%) achieved the target dose of their initial BB after adding ivabradine. NYHA functional class remained stable or improved in all cases. Conclusions: These results suggest that adding ivabradine to BB therapy may be an effective strategy to optimize heart rate control in patients with HF. This approach may improve BB tolerability, leading to greater target dose management and possibly better clinical outcomes.

Propranolol: A migraine prophylactic since the 1960s / Propranolol: um profilático para enxaqueca desde 1960

Introduction: Propranolol was the first non-selective beta-adrenergic blocker to be developed. Initially it was used in the treatment of cardiovascular diseases, but since the 60's it has been used in the prevention of migraine. Objective: The objective of this study was to know the history of propranolol and its use as a migraine prophylactic. Methods: This study was an integrative literature review using articles with historical data on propranolol, from its origin in cardiology to its indication in the preventive treatment of migraine. Results: Propranolol was described in 1962 for the treatment of cardiovascular diseases. In the same decade, it was prescribed for the preventive treatment of migraine and, recently, included in the consensus of the Brazilian Headache Society. Conclusion: Although propranolol was initially synthesized for the treatment of heart disease, it has proved to be an effective drug in preventing migraine attacks

Introdução: O propranolol foi o primeiro bloqueador beta-adrenérgico não seletivo a ser desenvolvido. Inicialmente era utilizado no tratamento de doenças cardiovasculares, mas desde a década de 60 tem sido utilizado na prevenção de enxaquecas. Objetivo: O objetivo deste estudo foi conhecer a história do propranolol e seu uso como profilático para enxaqueca. Métodos: Este estudo foi uma revisão integrativa da literatura utilizando artigos com dados históricos sobre o propranolol, desde sua origem na cardiologia até sua indicação no tratamento preventivo da enxaqueca. Resultados: O propranolol foi descrito em 1962 para o tratamento de doenças cardiovasculares. Na mesma década, foi prescrito para o tratamento preventivo da enxaqueca e, recentemente, incluído no consenso da Sociedade Brasileira de Cefaleia. Conclusão: Embora o propranolol tenha sido inicialmente sintetizado para o tratamento de doenças cardíacas, provou ser um medicamento eficaz na prevenção de crises de enxaqueca

Association between erectile dysfunction and the severity of obstruction to airflow in patients with chronic obstructive pulmonary disease / Asociación entre disfunción eréctil y la severidad de la obstrucción al flujo aéreo en pacientes con enfermedad pulmonar obstructiva crónica

Objectives: The objective of this study was to explore a possible association between ED and the severity of airflow obstruction in patients with COPD. Materials and methods: A cross-sectional study was conducted using the International Index Erectile Function (IIEF), a scale validated and translated to Spanish. Bivariate analyses between subgroups were made for quantitative variables using a t-test for means and Mann­Whitney U for medians; qualitative variables were compared using the χ2 test or Fisher's test, depending on distribution. Confusion bias in the association between ED and airflow obstruction was controlled using a logistic regression model. Results: The Spanish version of the IIEF-15 scale was valid and applicable to the Colombian population. The prevalence of ED in COPD patients living at high altitudes was similar to that found at sea level. Such prevalence is higher than in general population. Beta-blockers increased 7 times the risk of ED, but we found no association between the degree of airflow obstruction and ED. Conclusion: Although the severity of COPD is not associated with ED, the prevalence of ED in COPD is higher than in general population. Therefore, ED screening in COPD patients using the IIEF could be justified. The strong association between beta-blockers and ED had not been previously described in patients with COPD but must be considered in their clinical management.

Objetivos: Explorar una posible asociación entre DE y severidad de la obstrucción al flujo aéreo en pacientes con EPOC. Materiales y métodos: Estudio de corte transversal aplicando el Índice Internacional de Función Eréctil (IIFE), validado y traducido al español. Se realizó análisis bivariado para variables cuantitativas usando prueba-t para medias y U de Mann Whitney para medianas; las variables cualitativas fueron comparadas usando prueba de Chi2 o test de Fisher, según distribución. Los sesgos de confusión en la asociación entre DE y obstrucción al flujo aéreo fueron controlados usando un modelo de regresión logística. Resultados: La versión en español de la escala IIFE-15 fue aplicable en población colombiana. La prevalencia de DE en pacientes con EPOC viviendo a gran altura fue similar a lo encontrado a nivel del mar. Esta prevalencia es mayor que en población general. El uso de beta-bloqueadores aumentó hasta siete veces el riesgo de DE, pero no se encontró asociación entre el grado de obstrucción y la DE. Conclusiones: Aunque la severidad de la EPOC no está asociada con DE, la prevalencia de DE en EPOC es mayor que en población general. Está justificada la realización de tamizaje usando el IIFE. La asociación fuerte entre beta-bloqueadores y DE no se ha descrito previamente en pacientes con EPOC, pero debe considerarse en su manejo.

Short-Term Results of Ivabradine versus Metoprolol: The Effects on Atrial Fibrillation in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting

ABSTRACT Introduction: Classic coronary artery bypass grafting (CABG) surgery involves diastolic cardiac arrest under cardiopulmonary bypass, while off-pump CABG (OPCABG) has become widespread in recent years. Methods: 174 patients who underwent OPCABG were included in the study. Patients were divided into two groups. Group I (n=90) received ivabradine and Group M (n=84) received metoprolol before surgery until postoperative day 10. Intraoperative arrhythmias and hypotension were recorded. Postoperative atrial fibrillation (AF) and arrhythmia, mortality and morbidity rates were assessed based on the 30-day postoperative follow-up. Results: There were no significant differences in the intraoperative amount of inotropic support and red blood cell transfusion between groups (P=0.87 and P=0.31). However, the rates of intraoperative arrhythmias and hypotension were not significantly higher in Group M (P=0.317 and P=0.47). Ventricular tachycardia/ventricular fibrillation (VT/VF) was observed in 2 patients in both groups. Postoperative AF occurred in 7 patients (7.7%) in Group I and in 10 patients (11.9%) in Group M. Although there was a trend towards a higher prevalence of AF in Group M patients, this did not reach statistical significance. In addition, mortality and morbidity rates were comparable between groups.

Nationwide surveillance for S-Metoprololtreatment effect on blood pressure control against sympathetic overdrive in Indian patients with hypertension (PROTECT)

Background:Patients with hypertension in India been reported with high heart rate owing to sympathetic overdrive (SO). Beta-blockers provides several positive effects to reduce SO in patients with hypertension. The aim of present survey studywasto understand current real-world prevalence of SO in Indian patients with hypertension and usage of beta-blocker therapy in them.Methods:A cross sectional, observational, questionnaire-based survey conducted across India between June 2020 to October 2020. A specially designed validated questionnaire was shared with 157 registered health care practitioners (HCP),their anonymous inputs were captured and analysed in qualitative manner. Categorical data was summarized by number (n) and percentage (%). Results:Total 157 HCP participated and completed the survey. Around 53% of HCP observed that patients with average heart rate above 75 beats/min were associated with negative prognosis. Around 43% of HCP reported that raised heart rate is associated with advancedage and increased body mass index (BMI). Two-third of HCP reported that tachycardia is associated with stage-2 hypertension and marked by restlessness and anxiety which is suggestive of SO. Over 70% HCP agreed that the HR below 75 beats/min is associated with good prognosis. Around 89% HCP reported beta-blockers as the drug of choice in patients with augmented SO. S-Metoprololwas reported to bethemost preferred beta-blocker agent and was recommended by 76% HCP in patients with hypertension and coexisting SO.Conclusions:SO been reported prevalent conditionin Indian patients with hypertension which likely worsensthe prognosis in these patients. Beta-blockers reported to be the preferred choice of anti-hypertensive and S-Metoprololseem to be themost preferred agent amongst the available beta-blockers against SO in patients with hypertension in India.

Inhibition of toll-like receptor 4 inflammatory pathway by β-blocker attenuates myocardial injury in sepsis / 中华急诊医学杂志

Objective:To investigate the protective effect of β- blocker (esmolol) on myocardia and toll-like receptor 4 (TLR4) inflammatory pathway in septic rats.Methods:Sixty male Wistar rats were randomly (random number) divided into the shame group, sepsis group (CLP group), esmolol group (CLP+ES group) and TLR4 inhibitor group (CLP+TAK-242 group) with 15 rats in each group. Cecal exploration was performed in the shame group, and cecal ligation and perforation (CLP) was performed in the CLP group, CLP+ES group and CLP+TAK-242 group. The CLP+ES group received intraperitoneal injection of esmolol diluent 20 mg/kg 12 h after CLP. The CLP+TAK-242 group was given intraperitoneal injection of TAK-242 3 mg/kg at the same time point as above. The shame group and CLP group were given the same amount of normal saline. Rats in all groups were sacrificed 24 h after operation, and the samples were collected and processed. The pathological changes of myocardium were observed by hematoxylin - eosin staining. The expression of TLR4, myeloid differentiation protein 88 (MyD88) and nuclear factor -κB (NF-κB) in myocardial tissue were observed by immunohistochemistry. Masson staining was used to observe the expression of fibers and inflammatory factors in myocardial tissue. The protein expressions of TLR4, MyD88, NF-κB and aspartic acid specific cysteine protease 1 (caspase-1) were detected by Western blot. Serum levels of cardiac troponin I (cTn-I), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA).Results:Compared with the shame group, myocardial injury, fibrosis and inflammatory cell infiltration were significantly aggravated in the CLP group, and the levels of myocardial injury index cTn-I and inflammatory mediators TNF-α, IL-6 and IL-1β were significantly increased [(8.70±0.22) vs. (4.41±0.31), (445.57±9.13) vs. (219.60±5.52), (165.55±2.18) vs. (93.47±3.37), (124.12±2.59) vs. (67.63±6.04),all P<0.05]. Compared with the CLP group, myocardial injury was significantly reduced in the CLP+ES group and CLP+TAK-242 group, and the levels of inflammatory transmitters were significantly reduced [(5.38±0.18) and (5.37±0.13) vs. (8.70±0.22), (322.73±7.63) and (300.58±17.47) vs. (445.57±9.13), (121.28±5.44) and (120.30±4.95) vs. (165.55±2.18), (102.60±4.09) and (105.08±7.21) vs. (124.12±2.59), all P<0.05]. Western blot analysis showed that the protein expression levels of TLR4, MyD88, NF-κB and caspase-1 in the CLP group were significantly higher than those in the shame group [(1.79±0.15) vs. (1.15±0.04), (4.70±0.30) vs. (3.87±0.10), (0.35±0.04) vs. (0.18±0.02), (2.27±0.29) vs. (1.15±0.07), all P<0.05], while the protein expression levels in the CLP+ES group and CLP+TAK-242 group were significantly lower than those in the CLP group [(1.31±0.16) and (1.18±0.14) vs. (1.79±0.15), (1.50±0.16) and (1.46±0.19) vs. (2.27±0.29), (0.27±0.02) and (0.24±0.01) vs. (0.35±0.04), (1.50±0.16) and (1.46±0.19) vs. (2.27±0.29), all P<0.05]. Conclusions:β-blocker can reduce myocardial injury and inhibit the expression of inflammatory mediators in septic rats by blocking the inflammatory response mediated by TLR4 signaling pathway.

The Role of Beta-1 Receptor Gene Polymorphism in Beta-Blocker Therapy for Vasovagal Syncope

Background: Vasovagal syncope (VVS) is a common clinical condition involving genetic background. The role of beta-blockers in the treatment is controversial. Objective: The aim of this study was to investigate the effect of beta-1 gene polymorphism on beta-blocker therapy in patients with VVS. Methods: We included 123 patients who were diagnosed with VVS after the tilt-table test. We searched for the polymorphism Arg389Gly (rs1801253) in the beta-1 adrenoceptor gene. Results: Overall, 64 patients (52%) had Arg389Arg genotype and 59 patients (48%) had Arg389Gly genotype. The syncopal episodes of patients with Arg389Arg genotype were more frequent compared with patients having Arg389Gly genotype (total syncopal episodes [TSE], 7.9 ± 3.7 vs. 6.4 ± 3.0; p = 0.012). TSE in patients with Arg389Arg genotype decreased significantly after 18 months of beta-blocker treatment (7.9 ± 3.7 vs. 3.0 ± 1.4, p < 0.001). After 18 months of beta-blocker treatment, patients with Arg389Arg genotype had significantly fewer syncopal episodes than patients with Arg389Gly genotype (3.0 ± 1.4 vs. 6.8 ± 3.2, p < 0.001). Conclusions: Results of beta-blocker therapy in patients with Arg389Arg genotype suggest that VVS pathophysiology is a multifactorial condition, with genetic, psychological, and environmental components, and therefore, treatment selection can be based on gene polymorphism. (REV INVEST CLIN. 2020;72(5):300-7)

Research progress on the treatment of oral and maxillofacial hemangioma / 口腔疾病防治

@#Hemangioma is the most common vascular benign tumor in infants and young children, 60% of which occur in the oral maxillo-facial region. One characteristic of oral and maxillofacial hemangioma is spontaneous regression, which generally does not require treatment; however, a few hemangiomas can produce complications including ulceration, functional disorders and disfigurement, which require active treatments. Currently, the treatment of oral and maxillofacial hemangioma include drug treatment, laser treatment and surgical treatment. The drugs used to treat hemangioma mainly include beta blockers, glucocorticoids, alpha-interferon, imiquimod and antitumor drugs. Drug therapy is suitable for multiple, rapidly proliferating hemangiomas and hemangiomas that affect vital organ function or endanger life. Laser therapy can be applied to the early treatment of rapidly growing hemangiomas at exposed sites. Surgical treatment is suitable for proliferative hemangioma with serious complications, the reconstruction of any external deformity and the repair of a scar after an ulcer. Combined therapy and the development of new technologies provide new directions for the treatment of hemangioma but the efficacy remains to be proven by large sample prospective studies. Clinicians should appropriately evaluate the patients with hemangioma and develop individualized treatment programs for patients with treatment indications. This article reviews the efficacy, mechanism, clinical application and adverse reactions of different treatment methods and provides references for clinical treatment.

Effect of metoprolol in emergency treatment of chronic congestive heart failure / 中国基层医药

Objective To investigate the efficacy of metoprolol in the emergency treatment of chronic congestive heart failure.Methods From January 2016 to September 2018,300 cases of chronic congestive heart failure with acute attack in Zhoushan Hospital were selected.According to random number table method ,the patients were divided into two groups,with 150 cases in each group.The control group was given conventional heart failure treatment ,the observation group received conventional heart failure therapy combined with metoprolol.The clinical efficacy,heart color ultrasound indicator ,6 minutes walking distance ,NT－proBNP level,life quality score and adverse reactions were compared between the two groups.Results (1) The total effective rate of the observation group was 96.00%(141／150),which was higher than 87.33%(131／150) of the control group ( χ2 ＝7.375,P＜0.05).( 2) After treatment,the LVEDD[(58.12 ±3.89)mm],LVESD[(44.39 ±6.17) mm],NT－proBNP[(378.32 ±27.82)ng／mL] in the observation group were lower than those in the control group (t＝10.646,9.966,9.283,all P＜0.05),the LVEF [(49.36 ±6.25)%],SV[(76.29 ±6.24)mL] in the observation group were higher than those in the control group (t＝9.092,8.739,all P＜0.05).The 6－minute walking distance [(452.37 ±61.75) m] of the observation group was longer than that of the control group (t＝7.717,P＜0.05).The quality of life scores in the emotional field [(6.47 ± 1.29)points],physical field[(10.46 ±1.65)points],other fields[(10.51 ±1.32)points] and comprehensive score [(27.44 ±4.26) points] of the observation group were lower than those of the control group ( t＝9.030,9.024, 9.299,9.114,all P＜0.05).(3) During the treatment,no obvious adverse reactions occurred in the two groups. Conclusion In the emergency treatment of patients with chronic congestive heart failure,the application of conventional anti－heart failure treatment regimen metoprolol can effectively improve the patients＇heart function,and is conductive to improving their clinical efficacy and quality of life,with fewer adverse drug reactions and good safety.

Effect of metoprolol in emergency treatment of chronic congestive heart failure / 中国基层医药

Objective@#To investigate the efficacy of metoprolol in the emergency treatment of chronic congestive heart failure.@*Methods@#From January 2016 to September 2018, 300 cases of chronic congestive heart failure with acute attack in Zhoushan Hospital were selected.According to random number table method, the patients were divided into two groups, with 150 cases in each group.The control group was given conventional heart failure treatment, the observation group received conventional heart failure therapy combined with metoprolol.The clinical efficacy, heart color ultrasound indicator, 6 minutes walking distance, NT-proBNP level, life quality score and adverse reactions were compared between the two groups.@*Results@#(1)The total effective rate of the observation group was 96.00%(141/150), which was higher than 87.33%(131/150) of the control group (χ2=7.375, P<0.05). (2) After treatment, the LVEDD[(58.12±3.89)mm], LVESD[(44.39±6.17)mm], NT-proBNP[(378.32±27.82)ng/mL] in the observation group were lower than those in the control group (t=10.646, 9.966, 9.283, all P<0.05), the LVEF[(49.36±6.25)%], SV[(76.29±6.24)mL] in the observation group were higher than those in the control group(t=9.092, 8.739, all P<0.05). The 6-minute walking distance[(452.37±61.75)m] of the observation group was longer than that of the control group(t=7.717, P<0.05). The quality of life scores in the emotional field[(6.47±1.29)points], physical field[(10.46±1.65)points], other fields[(10.51±1.32)points]and comprehensive score[(27.44±4.26)points] of the observation group were lower than those of the control group(t=9.030, 9.024, 9.299, 9.114, all P<0.05). (3)During the treatment, no obvious adverse reactions occurred in the two groups.@*Conclusion@#In the emergency treatment of patients with chronic congestive heart failure, the application of conventional anti-heart failure treatment regimen metoprolol can effectively improve the patients' heart function, and is conductive to improving their clinical efficacy and quality of life, with fewer adverse drug reactions and good safety.

Metoprolol treatment of dual cocaine and bupropion cardiovascular and central nervous system toxicity

Cardiovascular and central nervous system (CNS) toxicity, including tachydysrhythmia, agitation, and seizures, may arise from cocaine or bupropion use. We report acute toxicity from the concomitant use of cocaine and bupropion in a 25-year-old female. She arrived agitated and uncooperative, with a history of possible antecedent cocaine use. Her electrocardiogram demonstrated tachycardia at 130 beats/min, with a corrected QT interval of 579 ms. Two doses of 5 mg intravenous metoprolol were administered, which resolved the agitation, tachydysrhythmia, and corrected QT interval prolongation. Her comprehensive toxicology screen returned positive for both cocaine and bupropion. We believe clinicians should be aware of the potential for synergistic cardiovascular and CNS toxicity from concomitant cocaine and bupropion use. Metoprolol may represent an effective initial treatment. Unlike benzodiazepines, metoprolol directly counters the pharmacologic effects of stimulants without respiratory depression, sedation, or paradoxical agitation. A lipophilic beta-blocker, metoprolol has good penetration of the CNS and can counter stimulant-induced agitation.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Chronopharmacology and drug prescribing pattern of physicians in a tertiary care hospital of North India

Background: Chronopharmacology is the science dealing with the optimization of drug effects and the minimization of adverse effects by timing medication in relation to the biological rhythm. This concept came into picture to make us understand about periodic and predictable changes in both desired effects and tolerance of medication Chronotherapeutics approach gives more accurate determination of the time when patients are at highest risk and in greatest need of therapy. This Chronopharmacological principle is used in the therapy of various diseases like cardiovascular diseases, allergy and many more. The objective of the study was to analyse whether chronopharmacological approach was being applied in clinical practice by comparing chronopharmacology of 4 drugs to their prescribing pattern by the physicians.Methods: This was observational study where 700 prescriptions written by physicians were audited. To study all the drugs would have been tedious so four commonly used drugs were chosen that is, Proton pump inhibitors, statins, Beta blockers and subcutaneous Insulin.Results: Results showed that chronopharmacological approach has been applied in the clinical field though physician didn’t have clear concept about chronopharmacology and it is relation to the prescribing. Despite this, maximum physician prescribing pattern was comparable to the chronopharmacological data except in case of Proton pump inhibitors.Conclusions: It is concluded that Chronotherapeutics approach gives more accurate determination of the time when patients are at highest risk and in greatest need of therapy. Nevertheless, this variation is only seldom considered by clinicians. If drugs are prescribed by following chronopharmacological approach it can prove beneficial to the patients as more of effectiveness of the drug and lesser side effects.

Heart rate manipulation in dilated cardiomyopathy: Assessing the role of Ivabradine

Background Heart rate (HR) reduction is of benefit in chronic heart failure (HF). The effect of heart rate reduction using Ivabradine on various echocardiographic parameters in dilated cardiomyopathy has been less investigated. Methods Of 187 patients with HF (DCM, NYHA II–IV, baseline HR > 70/min), 125 patients were randomized to standard therapy (beta blockers, ACEI, diuretics, n = 62) or add-on Ivabradine (titrated to maximum 7.5 mg BD, n = 63). Beta-blockers were titrated in both the groups. Results At 3 months both groups had improvement in NYHA class, 6 min walk test, Minnesota Living With Heart Failure (MLWHF) scores and fall in BNP, however the magnitude of change was greater in Ivabradine group. Those on Ivabradine also had lower LV volumes, higher LVEF (28.8 ± 3.6 vs 27.2 ± 0.5, p = 0.01) and more favorable LV global strain (11 ± 1.7vs 12.2 ± 1.1, p = <0.001), MPI (0.72 ± 0.1 vs 0.6 ± 0.1, p = <0.001), LV mass (115.2 ± 30 vs 131.4 ± 35, p = 0.007), LV wall stress (219.8 ± 46 vs 238 ± 54) and calculated LV work (366 ± 101 vs 401 ± 102, p = 0.05). The benefit of Ivabradine was sustained at 6 months follow up. The % change in HR was significantly higher in Ivabradine group (−32.2% vs −19.3%, p = 0.001) with no difference in blood pressure. Resting HR < 70/min was achieved in 96.8% vs 27.9%, respectively in the two groups. Conclusion Addition of Ivabradine to standard therapy in patients with DCM and symptomatic HF and targeting a heart rate < 70/min improves symptoms, quality of life and various echocardiographic parameters.

Impact of Heart Rate Reduction with Maximal Tolerable Dose of Bisoprolol on Left Ventricular Reverse Remodeling

BACKGROUND: We aimed to evaluate effect of heart rate (HR) reduction on left ventricular reverse remodeling (LVRR) in Korean patients with heart failure with reduced ejection fraction (HFrEF). METHODS: Ambulatory patients with HFrEF, who had paired echocardiograms, N-terminal prohormone brain natriuretic peptide (NT-proBNP), and global assessment score (GAS) at baseline and 6-month (n = 157), were followed up on preset treatment schedule with bisoprolol. RESULTS: The LVRR occurred in 49 patients (32%) at 6-month. In multivariable analysis, independent predictors associated with LVRR were use of anti-aldosterone agent (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.80–9.71), young age (OR, 0.96; 95% CI, 0.92–0.99), high baseline HR (OR, 3.76; 95% CI, 1.40–10.10), and favorable baseline GAS (OR, 1.73; 95% CI, 1.06–2.81). Beneficial effect of bisoprolol, in terms of LVRR, NT-proBNP, and GAS, was remarkable in the high HR group (baseline HR ≥ 75 beats per minute [bpm]), which showed a large HR reduction. CONCLUSION: High baseline HR (≥ 75 bpm) showed an association with LVRR and improvement of NT-proBNP and GAS in patients with HFrEF. This seems to be due to a large HR reduction after treatments with bisoprolol. Trial registry at www.ClinicalTrials.gov, NCT00749034.

Clinical efficacy of combined beta blocker in the treatment of chronic severe congestive heart failure / 中国生化药物杂志

Objective To investigate the clinical efficacy of combined use of beta blocker in the treatment of chronic severe congestive heart failure (CHF). Methods 78 patients with severe chronic congestive heart failure in patients from November 2015 to January 2017 were randomly divided into study group (n=39) and control group (n=39). The control group was treated with routine treatment of chronic severe congestive heart failure, and the study group was treated with beta blocker metoprolol on the basis of routine treatment. The changes of DBP, SBP, LVEF, LVEDD and the incidence of adverse reactions were recorded before and after treatment in two groups. Results After the analysis of the two groups before treatment, DBP, SBP, LVEF, LVEDD and other indicators compared no significant difference; after the treatment of DBP, SBP, LVEDD group index decline and increase of LVEF were better than the control group, comparing the data with significant difference (P<0.05); drug therapy in the treatment of severe chronic group occurred during the study period the rate of adverse reactions in patients with congestive heart failure and there is no significant difference compared with control group. Conclusion The use of routine regimen based on the use of beta blocker metoprolol can significantly improve the clinical efficacy of patients with chronic severe congestive heart failure, and is conducive to the protection of their prognosis and quality of life.

Clinical efficacy of combined beta blocker in the treatment of chronic severe congestive heart failure / 中国生化药物杂志

Objective To investigate the clinical efficacy of combined use of beta blocker in the treatment of chronic severe congestive heart failure (CHF). Methods 78 patients with severe chronic congestive heart failure in patients from November 2015 to January 2017 were randomly divided into study group (n=39) and control group (n=39). The control group was treated with routine treatment of chronic severe congestive heart failure, and the study group was treated with beta blocker metoprolol on the basis of routine treatment. The changes of DBP, SBP, LVEF, LVEDD and the incidence of adverse reactions were recorded before and after treatment in two groups. Results After the analysis of the two groups before treatment, DBP, SBP, LVEF, LVEDD and other indicators compared no significant difference; after the treatment of DBP, SBP, LVEDD group index decline and increase of LVEF were better than the control group, comparing the data with significant difference (P<0.05); drug therapy in the treatment of severe chronic group occurred during the study period the rate of adverse reactions in patients with congestive heart failure and there is no significant difference compared with control group. Conclusion The use of routine regimen based on the use of beta blocker metoprolol can significantly improve the clinical efficacy of patients with chronic severe congestive heart failure, and is conducive to the protection of their prognosis and quality of life.

Effects of dorzolamide/timolol and tafluprost on intraocular pressure and pupil diameter in healthy dogs / Efeitos da dorzolamida/timolol e da tafluprosta sobre a pressão intraocular e o diâmetro pupilar em cães saudáveis

ABSTRACT: This study aimed to evaluate and compare the effects of the fixed combination of dorzolamide/timolol with those of tafluprost on intraocular pressure (IOP) and pupil diameter (PD) in healthy dogs (n=10). Two experiments were conducted with an interval of 30 days. In both, IOP and PD were assessed at 8, 11, 14, 17, and 20h. Parameters were evaluated during baseline, treatment period of four days, and one day of post-treatment. During treatment phase, IOP decreased by 0.74 (P<0.05), 1.88 (P<0.01), 2.94 (P<0.001), and 3.10mmHg (P<0.01), in dorzolamide/timolol-treated eyes; and by 1.50, 2.18, 2.14, and 2.18mmHg (P<0.001), in tafluprost-treated eyes. PD decreased by 0.24 (P<0.01), 0.32 (P<0.01), 0.49 (P<0.001), and 0.40mm (P<0.001), in dorzolamide/timolol treated eyes; and by 2.31, 2.55, 2.43, and 2.70mm (P<0.001), in tafluprost-treated eyes. Dorzolamide/timolol and tafluprost were able to decrease IOP and PD in healthy dogs. However, a cumulative effect of the fixed combination of dorzolamide/timolol was more effective in reducing IOP, than tafluprost. Comparisons between treatments showed that tafluprost was more effective in reducing PD throughout the treatment phase.

RESUMO: O estudo objetivou avaliar e comparar os efeitos da combinação fixa da dorzolamida/timolol com os da tafluprosta sobre a pressão intraocular (PIO) e o diâmetro pupilar (DP) em cães saudáveis (n=10). Dois experimentos com intervalo de 30 dias foram conduzidos. Em ambos, a PIO e o DP foram avaliados às 8, 11, 14, 17 e às 20h. Os parâmetros foram avaliados durante a fases basal, um período de tratamento de quatro dias, e um dia de pós-tratamento. Durante a fase de tratamento, a PIO dos olhos tratados com dorzolamida/timolol reduziram em 0.74 (P<0.05), 1.88 (P<0.01), 2.94 (P<0.001), e 3.10mmHg (P<0.01); e dos olhos tratados com tafluprosta em 1.50, 2.18, 2.14 e 2.18mmHg (P<0.001). O DP dos olhos tratados com dorzolamida/timolol reduziram em 0.24 (P<0.01), 0.32 (P<0.01), 0.49 (P<0.001) e 0.40mm (P<0.001); e dos olhos tratados com tafluprosta em 2.31, 2.55, 2.43 e 2.70mm (P<0.001). A dorzolamida/timol e a tafluprosta foram capazes de reduzir a PIO e o DP em cães saudáveis. Porém, efeito cumulativo do tratamento com dorzolamida/timolol foi observado, decorridos três dias de tratamento. Por essa razão, a dorzolamida/timolol foi mais efetiva que a tafluprosta na redução da PIO. Comparações entre os tratamentos demonstraram que a tafluprosta foi mais efetiva em reduzir o DP, durante toda a fase de tratamento.