Atenolol Group Research Articles

B1-adrenergic blockers preserve motor function by inhibiting the production of extracellular traps

Sepsis is characterized by a dysregulated host response to an infection, potentially leading to fatal organ dysfunctions. Among these organs, the central nervous system (CNS) is particularly affected with encephalopathies associated or not with chronic disabling pain. These symptoms are caused by broad neuroinflammation with activation of resident microglia cells and infiltration of leukocytes, especially neutrophils. These immune cells have the ability to produce extracellular traps (ETs) in blood and tissues. These components are composed of chromatins and various antimicrobial proteins, and its role is to capture and destroy pathogens. However, in case of excessive production, deleterious effects occur such as tissue damage and reduction of neuronal excitability.In this study, the objectives were: 1) to determine whether in a model of endotoxemic shock, neutrophils and microglia form ETs in the CNS; 2) and to determine if a modulation of ETs production was beneficial on neuromuscular disorders associated with endotoxemic shock.We observed an infiltration of neutrophils in the SNC, an activation of microglia and a production of ETs following intraperitoneal lipopolyssacharide (LPS) administration in mice (adult Swiss male, 30-45g). Atenolol, a β1-adrenergic blocker with intrinsic immunomodulatory properties, significantly decreases the production of ETs associated in both microglia and neutrophils (citrullinated histone H3: 279.1 ± 101.9 MFI versus 117.1 ± 77.21 MFI, p<0,01). In addition, this treatment preserved the gastrocnemius motoneurons excitability (39,93 ± 15,16 mV in control group, 8.147 ± 5.892 mV in LPS group and 27.32 ± 10.73 mV in LPS+atenolol group). Similar results have been observed when the production of ETs was prevented by using sivelestat (inhibitor of extracellular traps).In conclusion, our results demonstrate that sepsis increases neutrophil infiltration into the spinal cord, activates immune cells and produces extracellular traps that directly impair motor function. Prevention of ETs formation partly restores motor function and could be a good target in order to reduce adverse effects in sepsis but also in other motor related pathologies. This work was supported by funding from the Chancellerie des Universites de Paris (Legs Poix), INSERM and Paris-Saclay University-UVSQ. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparing the Effectiveness of Propranolol versus Atenolol in Inducing Clinical Clearance in the Treatment of Infantile Haemangioma: A Randomised Controlled Trial.

Despite the excellent clinical efficacy of oral propranolol in the management of infantile haemangiomas (IHs), there is a need to further evaluate other beta blockers that may be equally efficacious but result in lesser adverse effects. We compared the efficacy and short-term safety of atenolol, a hydrophilic cardio-selective beta blocker, with propranolol, in the treatment of IHs. Sixty patients with complicated and/or cosmetically significant IHs were randomised into two groups, oral propranolol group (2 mg/kg/day) and the oral atenolol (1 mg/kg/day) group, respectively, for 9 months. Patients were assessed clinically, by the use of Doppler ultrasonography (USG) and measurement of serum hypoxia-inducible factor 1 alpha (HIF-1α). Twenty-two of 30 patients achieved complete clearance in the propranolol group (0.73; 95% CI = 0.54 to 0.87) compared with 13 of 25 patients in the atenolol group (0.52; 95% CI = 0.31 to 0.72). The mean time to achieve Physician Global Assessment Score 5 (PGA5) (25.00 ± 8.87 weeks) was significantly lesser in the propranolol group versus the atenolol group (31.69 ± 7.01 weeks; log-rank = 0.04). The two groups were comparable in terms of adverse effect profile, degree of volume reduction in USG and reduction in HIF-1α levels. Propranolol (2 mg/kg/day) is better than atenolol (1 mg/kg/day) in inducing complete clinical clearance of IH although the results need to be reproduced in larger studies.

THE EFFECT OF ANTI HYPERTENSIVE DRUGS ON TEAR SECRETION AND STABILITY

Hypertension is a chronic medical condition in which blood pressure in the arteries is elevated. This research work studied the effect of antihypertensive drugs specifically beta adrenergic blockers (atenolol) and angiotensin converting enzymes (lisinopril) on tears secretion and stability in adults. A total of 75 people (35 65years) male and female participated and completed the study with a mean age of 52.8±1.83years. These subjects were divided into group A (control) comprised of 25 normotensive subjects; group B (experimental) which comprised of 25 hypertensive subjects on atenolol alone (beta blocker) and group C (experimental) comprised of 25 hypertensive subjects on lisinopril (angiotensin converting enzymes ) alone .Tear volume was determined using schirmer strips and tear stability was determined using fluroscein strip. These patients were examined for all the tests at first week (baseline) and repetition of all tests one week later after oral drug administration of atenolol (Group B) or lisinopril (Group C). When the tear break up at time baseline and follow up measurement of group B were compared, it was observed that there was a statistically significant decrease (P<0.05). When the tear breakup time at baseline and follow up measurements of Group C were compared, it was observed that there was a statistically significant decreased.(P<0.05) The use of antihypertensive drugs atenolol (beta blocker) has an effect on the tear break up time. Also lisinopril (angiotensin converting enzyme inhibitor) has an effect on tear break time.

Design, synthesis and preclinical evaluations of (s)-2-((s)-1-benzyl-2,5-dioxopyrrolidin-3-yl)-3-(4-isopropylphenyl)-2-methylpropanal (succ-5) as cardioprotective, hepatoprotective and lipid lowering molecule. in-vivo and in-silico approaches

In this study, the newly synthesized compound (Succ-5) was analyzed through spectral methods, seen for potential receptor targets via molecular docking, and pre-clinically evaluated for therapeutic effects and safety profile using biochemical and histopathological techniques. The biochemical analysis included assessment of cardiac biomarkers, hepatic enzymes, and lipid profiles, while histopathology included evaluation of cardiac and liver tissues. The toxic dose was determined pre-clinically, followed by dividing albino rats into five treatment groups (each having n = 6). The control group received oral saline for eight days. The 5-FU (5-Fluorouracil) group received oral saline for 8 days and 5-FU (150 mg/kg I.P.) on day 5.The atenolol group was administered with atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5. Two groups of rats were administered with the test compound (Succ-5) at doses of 5 mg/kg I.P and 10 mg/kg I.P (for 8-days), followed by 5-FU (150 mg/kg I.P.) on day 5. Elevated serum levels of CK-MB (creatinine kinase myocardial band), cTnI (troponin I), LDH (lactate dehydrogenase), lipid profile, and selected liver enzymes including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total) and BD (direct bilirubin) were associated with 5-FU toxicity. After administration of the test compound at the mentioned doses, these biomarkers significantly decreased. Likewise, histological examination revealed 5-FU damaged the heart and hepatic tissues, which were also considerably recovered following administration of the test compound. Immunohistochemistry of heart tissue also revealed the low expression of COX-2 and TNF-α in Succ-5 treated groups compared to toxic group. Dose-response evaluation showed that a dose of 10 mg/kg provided better results than 5 mg/kg. The analysis of binding energy values computed via docking simulations showed that Succ-5 interacts with the human beta2-adrenergic G protein-coupled receptor with a slightly stronger affinity than calcium channel T-type. In conclusion, the histological and biochemical findings revealed that the test compound had significant cardioprotective, hepatoprotective, and lipolytic effects in the 5-FU-induced toxicity.

Long-term neurocognitive functioning of children treated with propranolol or atenolol for infantile hemangioma

The purpose of this study was to compare long-term neurocognitive functioning (working memory, processing speed, and attention) between children who had been treated with either propranolol or atenolol for infantile hemangioma during infancy. All eligible children (n = 158) aged 6 years or older and treated with propranolol or atenolol as infants were invited to participate in this two-center cross-sectional study. The primary outcome was the Wechsler Intelligence Scale for Children-V Cognitive Proficiency Index (CPI), a measure of working memory, processing speed, and attention. Secondary outcomes were general intelligence, auditory, visuospatial, and narrative memory, as well as executive functioning and sleep. A total of 105 children, of whom 36 had been treated with propranolol (age 6.0–11.8 years, follow-up time 1.6–9.7 years, 19% male) and 69 had been treated with atenolol (age 6.9–9.7 years, follow-up time 4.5–8.4 years, 19% male), were analyzed. The CPI and other neurocognitive outcomes did not differ between the propranolol and atenolol groups and were in line with general population test norms. Post hoc analyses revealed lower CPI scores for males, both compared to participating females (10.3 IQ points, medium effect size) and compared to matched test norms (12.4 IQ points, medium effect size).Conclusions: Long-term neurocognitive functioning did not differ between children treated with propranolol and those treated with atenolol for IH. Overall, propranolol and atenolol appear to be safe treatments for IH regarding long-term neurocognitive functioning. The substantially lower CPI scores in males warrant further investigation.Trial registration: Netherlands Trial Register, NL7703 https://www.trialregister.nl/trial/7703What is Known:• Infants with infantile hemangioma are effectively treated with propranolol or atenolol.• Parents and professionals are concerned about long-term neurocognitive effects.What is New:• No long-term (≥ 6 years) differences in neurocognitive functioning were found between children treated with propranolol or atenolol.• Males treated with beta-blockers had substantially lower IQ scores than treated females and males from the general population, which is a matter of concern and should be considered when evaluating the risk/benefit ratio in less severe forms of infantile hemangioma.

“A comparative study of Nebivolol plus Amlodipine and Atenolol plus Amlodipine on blood pressure and heart rate in patients of essential hypertensive patients”

Objectives: Study was conducted to compare the evaluation of efficacy and safety of Nebivolol plus Amlodipine combination with Atenolol plus Amlodipine combination in hypertensive patients.Materials and Methods: A Prospective Observational study was conducted at tertiary care teaching hospital which included a total 334 patients with essential hypertension. The demographic and baseline data, Blood pressure and Heart rate of the patients were recorded. After baseline investigation patients were randomly divide into 2 groups. All patients were subsequently monitored and reassessed at 4th-week, 8th week and 12th weeks of interval during each follow-up.Results: Nebivolol plus Amlodipine group include a total 169 patients in which 129 patients were males and 40 patients were females with mean age 46.89 ±12.48 years, Atenolol plus Amlodipine group include a total 165 patients in which 111patients were males and 54 patients were females with mean age 48.19±12.14 years. Patients were receiving Nebivolol plus Amlodipine and Atenolol plus Amlodipine showed a significant fall in systolic blood pressure (SBP), Diastolic blood pressure (DBP) and Heart rate at the end of 4th, 8th and 12th weeks of interval as compared to their baseline data.Conclusion: A Study revels that Reduction of blood pressure and Heart rate were similar in both treatment groups (Nebivolol plus Amlodipine and Atenolol plus Amlodipine).(P- value >0.05)

Synthesis, Molecular Docking, and Preclinical Evaluation of a New Succinimide Derivative for Cardioprotective, Hepatoprotective and Lipid-Lowering Effects.

Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg/kg I.P. and 10 mg/kg I.P. for 8 days, followed by 5-FU (150 mg/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg/kg and 10 mg/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = −7.89 kcal/mol) with a slight stronger affinity than the calcium channel T-type (S = −7.07 kcal/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.

Investigating the biological degradation of the drug β-blocker atenolol from wastewater using the SBR.

Drug compounds are one of the main contributors to the entry of micro-pollutants into the environment, known as a constant threat to environmental stability. Atenolol is a type of beta-blocker extensively used to cure cardiovascular disorders. The residues of this compound have been continuously detected in aquatic environments because it is a polar and poorly biodegradable compound. Thus, removing atenolol from wastewater is essential before discharging into the environment. Biological processes are considered the most important removal process for polar drugs in wastewater treatment plants. Accordingly, for the first time in this study, the SBR performance was investigated in the biodegradation and mineralization of atenolol under different concentrations (50-600mg/L) and hydraulic retention times (48-32h). Based on the results, the time required for the acclimation of biomass to atenolol (C: 50mg/L and the HRT: 48h) was 80 days. The SBR efficiencies under optimum conditions (C: 400mg/L and HRT: 40h) in removing the atenolol and COD were 91% and 87%, respectively. For the first time in this study, one of the main pathways of the atenolol biodegradation was identified. Based on the review and comparison of the results of this study with existing literature showing that the SBR used in this study was able to remove higher concentrations with better efficiencies than other processes. Therefore, it can be concluded that the SBR used in this study could be considered an efficient and promising technique for treating wastewaters containing atenolol and other beta-blocker group drugs.

Should Propranolol Remain the Gold Standard for Treatment of Infantile Hemangioma? A Systematic Review and Meta-Analysis of Propranolol Versus Atenolol.

Although propranolol has been established as the gold standard when treatment is sought for infantile hemangioma, concerns over its side effect profile have led to increasing usage of atenolol, a beta-1 selective blocker. A systematic review of PubMed, Scopus, CINAHL, Google Scholar, and Cochrane was conducted following PRISMA guidelines using MeSH terms and keywords for the terms propranolol, atenolol, and infantile hemangioma, including alternative spellings. All randomized control trials (RCTs) or cohort studies directly comparing outcomes of hemangioma treatment with atenolol and propranolol were included. A meta-analysis with pooled mean differences, pooled odds ratios, and analysis of proportions was performed. A total of 669 participants in 7 studies (3 RCTs and 4 cohort) were included. Propranolol showed a significantly higher rate of complete response compared to atenolol (73.3% vs 85.4%, P = .0004). The pooled mean difference of 0.07 (95% CI -0.12, 0.27) in Hemangioma Activity Score (HAS) was not statistically significant. In terms of side effects, there were significantly more agitation and bronchial hyperreactivity events in the propranolol group (P = .0245 and P < .0001, respectively). Overall, there was a significantly greater number of adverse events in the propranolol group compared to the atenolol group (185 vs 117, P < .00001). The overall pooled odds ratio was 2.70 (95% CI 1.90, 3.84), indicating that there is 2.7 times higher odds of adverse events in the propranolol group. Propranolol treatment leads to a significantly higher rate of complete response than atenolol. However, its use must be weighed against its greater side effect profile.

English

BACKGROUND Bleeding during functional endoscopy sinus surgery (FESS) remains a main consideration. Even a small amount of blood may disturb the endoscopic view, increasing the likelihood of complications. So, we decided to compare the effects of clonidine and atenolol as oral premedication for hypotensive anaesthesia in patients undergoing FESS under general anaesthesia. The purpose of this study was to analyse and compare the efficacy of oral atenolol versus oral clonidine as premedication under general anaesthesia for induced hypotension in patients undergoing a functional endoscopic sinus surgery. METHODS The study included total 100 patients of age (18 – 60 years) [American Society of Anaesthesiologists (ASA grade I and II)] who were randomly divided into two groups of 50 each. Group - A (n = 50), a non-labelled clonidine tablet PO was given to the patients in the clonidine group in the dose of 2 mcg/kg at 7 pm the day before surgery and 4 mcg/kg two hours before surgery. Group - B (n = 50), a non-labelled atenolol 25 mg tablet was given PO to the patients in the atenolol group at 7 pm the day before surgery and also 2 hours before surgery. Induction and maintenance of general anaesthesia was performed by the same standard protocol for both groups. Hemodynamic effects [heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), quality of surgical field, intraoperative complications, and post anaesthetic discharge score system (PADSS)] were recorded and statistically analysed. RESULTS The hemodynamic stability and good quality surgical field was obtained in both the groups. The lesser incidence of intraoperative complications recorded with atenolol gives it a more favourable profile when compared to clonidine. CONCLUSIONS We conclude that both oral clonidine and atenolol premedication provides superior and predictable perioperative hemodynamic control, reduces the requirement of hypotensive agents, and produces acceptable recovery characteristics. The lesser incidence of intraoperative complications recorded with atenolol gives it a more favourable profile when compared to clonidine. KEYWORDS Atenolol, Clonidine, Functional Endoscopic Sinus Surgery (FESS)

Efficacy and Safety of Propranolol vs Atenolol in Infants With Problematic Infantile Hemangiomas

Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been reported during propranolol treatment. The positive efficacy and safety of atenolol raise the question of whether it could be used as a promising therapy for IH. To compare the efficacy and safety of propranolol vs atenolol in infants (between age 5 and 20 weeks) with problematic IHs who required systemic therapy. This was a prospective, multicenter, randomized, controlled, open-label clinical trial conducted in collaboration among 6 separate investigation sites in China from February 1, 2015, to December 31, 2018. A total of 377 patients met the criteria for inclusion and were randomized to the propranolol (190 [50.4%]) and atenolol (187 [49.6%]) groups. Data were analyzed in June 2020. Participants were randomized to receive either propranolol or atenolol for at least 6 months. They completed efficacy assessments at 2 years after the initial treatment. The primary outcome was any response or nonresponse at 6 months. The key secondary outcome was changes in the hemangioma activity score. Of 377 participants, 287 (76.1%) were female, and the mean (SD) age was 10.2 (4.0) weeks in the propranolol group and 9.8 (4.1) weeks in the atenolol group. After 6 months of treatment, in the propranolol and atenolol groups, the overall response rates were 93.7% and 92.5%, respectively (difference, 1.2%; 95% CI, -4.1% to 6.6%). At 1 and 4 weeks after treatment, and thereafter, the hemangioma activity score in the atenolol group aligned with the propranolol group (odds ratio, 1.034; 95% CI, 0.886-1.206). No differences between the propranolol group and atenolol group were observed in successful initial responses, quality of life scores, complete ulceration healing times, or the rebound rate. Both groups presented a similar percentage of complete/nearly complete responses at 2 years (82.1% vs 79.7%; difference, 2.4%; 95% CI, -5.9% to 10.7%). Adverse events were more common in the propranolol group (70.0% vs 44.4%; difference, 25.6%; 95% CI, 15.7%-34.8%), but the frequency of severe adverse events did not differ meaningfully between the groups. In this randomized clinical trial, when compared with propranolol, atenolol had similar efficacy and fewer adverse events in the treatment of infants with problematic IHs. The results suggest that oral atenolol can be used as an alternative treatment option for patients with IH who require systemic therapy. ClinicalTrial.gov Identifier: NCT02342275.

Effects of β‐adrenoceptor activation on haemodynamics during hypoxic stress in rats

What is the central question of this study? The acute hypoxic compensatory reaction is based on haemodynamic changes, and β-adrenoceptors are involved in haemodynamic regulation. What is the role of β-adrenoceptors in haemodynamics during hypoxic exposure? What is the main finding and its importance? Activation of β2 -adrenoceptors attenuates the increase in pulmonary artery pressure during hypoxic exposure. This compensatory reaction activated by β2 -adrenoceptors during hypoxic stress is very important to maintain the activities of normal life. The acute hypoxic compensatory reaction is accompanied by haemodynamic changes. We monitored the haemodynamic changes in rats undergoing acute hypoxic stress and applied antagonists of β-adrenoceptor (β-ARs) subtypes to reveal the regulatory role of β-ARs on haemodynamics. Sprague-Dawley rats were randomly divided into control, atenolol (β1 -AR antagonist), ICI118,551 (β2 -AR antagonist) and propranolol (non-selective β-AR antagonist) groups. Rats were continuously recorded for changes in haemodynamic indexes for 10min after administration. Then, a hypoxic ventilation experiment [15% O2 , 2200 m a.sl., 582 mmHg (0.765 Pa), 87.3 mmHg; Xining, China] was conducted, and the indexes were monitored for 5min after induction of hypoxia. Plasma catecholamine concentrations were also measured. We found that, during normoxia, the mean arterial pressure, heart rate, ascending aortic blood flow and pulmonary artery pressure were reduced in the propranolol and atenolol groups. Catecholamine concentrations were increased significantly in the atenolol group compared with the control group. During hypoxia, mean arterial pressure and total peripheral resistance were decreased in the control, propranolol and ICI118,551 groups. Pulmonary arterial pressure and pulmonary vascular resistance were increased in the propranolol and ICI118,551 groups. During hypoxia, catecholamine concentrations were increased significantly in the control group, but decreased in β-AR antagonist groups. In conclusion, the β2 -AR is involved in regulation of pulmonary haemodynamics in the acute hypoxic compensatory reaction, and the activation of β2 -ARs attenuates the increase in pulmonary arterial pressure during hypoxic stress. This compensatory reaction activated by β2 -ARs during hypoxic stress is very important to maintain activities of normal life.

Atenolol vs. propranolol for the treatment of infantile haemangiomas: A systematic review and meta-analysis.

Infantile haemangioma (IH) is a benign vascular tumour type that occurs in 3-10% of infants. In the present meta-analysis, previous studies comparing clinical outcomes, including the recovery rate and haemangioma activity score (HAS), adverse effects and relapse rates, were compared between patients treated with atenolol and those treated with propranolol for IH. A systematic search in various databases, including Medline, Cochrane Controlled Register of Trials, ScienceDirect and Google Scholar from inception until July 2019 was performed. The Cochrane risk of bias tool was used to assess the quality of published trials. A meta-analysis with a random-effects model and reported pooled mean differences (MD) or odds ratios (OR) with 95% CIs was performed. In total, 8 studies including 608 participants were analyzed. Only 2 studies were randomized controlled trials, while the majority of studies had low or unclear bias risks. Except for the response to medication (pooled OR=1.49; 95% CI, 0.85-2.18), all other outcomes (HAS, adverse reactions and relapse rate) were better for the atenolol group than the propranolol group. Atenolol resulted in better HAS (pooled MD=0.16; 95% CI, -0.42 to 0.73). Propranolol had more adverse reactions (pooled OR=2.17; 95% CI, 0.93-5.06) and a higher relapse rate (pooled OR, 1.67; 95% CI, 0.44-6.41) when compared to atenolol. However, these findings were not statistically significant. The results of this analysis suggest that atenolol may be non-inferior to propranolol and may offer advantages, including lower adverse reactions and relapse rates.

The role of atenolol in the modulation of the expression of genes encoding pro- (caspase-1) and anti- (Bcl2L1) apoptotic proteins in endothelial cells exposed to intestinal ischemia and reperfusion in rats.

To investigate the role of atenolol in the gene expression of caspase 1 (Casp1) and Bcl2L1 on vascular endothelium of rat intestine after ischemia and reperfusion (IR). Eighteen adult male Wistar rats were randomly divided into 3 groups (n=6): SG (Sham group): no clamping of the superior mesenteric artery; IRG: IR plus saline group: IRG+At: IR plus Atenolol group. Rats from IRG and IRG+At were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. Atenolol (2mg/kg) or saline were injected in the femoral vein 5 min before ischemia, 5 min and 55 min after reperfusion. Thereafter, intestinal segments were appropriately removed and processed for Endothelial Cell Biology Rat RT2 Profiler PCR Array. the anti-apoptotic Bcl2L1 gene expression was significantly down-regulated (-1.10) in the IRG and significantly up-regulated in the IRG+At (+14.15). Meanwhile, despite Casp1 gene expression was upregulated in both groups, it was significantly higher in the IRG (+35.06) than the IRG+At (+6.68). Atenolol presents antiapoptotic effects on rat intestine subjected to IR partly by the up-regulation of the anti-apoptotic Bcl2L1 gene expression. Moreover, atenolol can mitigate the pro-apoptotic and pro-inflammatory effects of Casp1 gene on rat intestine after IR.

Losartan Versus Atenolol for Prevention of Aortic Dilation in Patients With Marfan Syndrome

BackgroundBeta-blockers are the standard treatment in Marfan syndrome (MFS). Recent clinical trials with limited follow-up yielded conflicting results on losartan’s effectiveness in MFS. ObjectivesThe present study aimed to evaluate the benefit of losartan compared with atenolol for the prevention of aortic dilation and complications in Marfan patients over a longer observation period (>5 years). MethodsA total of 128 patients included in the previous LOAT (LOsartan vs ATenolol) clinical trial (64 in the atenolol and 64 in the losartan group) were followed up for an open-label extension of the study, with the initial treatment maintained. ResultsMean clinical follow-up was 6.7 ± 1.5 years. A total of 9 events (14.1%) occurred in the losartan group and 12 (18.8%) in the atenolol group. Survival analysis showed no differences in the combined endpoint of need for aortic surgery, aortic dissection, or death (p = 0.462). Aortic root diameter increased with no differences between groups: 0.4 mm/year (95% confidence interval: 0.2 to 0.5) in the losartan and 0.4 mm/year (95% confidence interval: 0.3 to 0.6) in the atenolol group. In the subgroup analyses, no significant differences were observed considering age, baseline aortic root diameter, or type of dominant negative versus haploinsufficient FBN1 mutation. ConclusionsLong-term outcome of Marfan syndrome patients randomly assigned to losartan or atenolol showed no differences in aortic dilation rate or presence of clinical events between treatment groups. Therefore, losartan might be a useful, low-risk alternative to beta-blockers in the long-term management of these patients.

Effect of Premedication with Clonidine vs. Atenolol in Providing Optimum Surgical Field in Spine Fusion Surgery Under General Anaesthesia

AbstractBackground: Spine surgeries are associated with significant blood loss, which vary from 10 to 30mL/kg and its volume depends on the number of spinal levels fused; body weight, surgery for tumors, and raised intra-abdominal pressure in the prone position. Blood loss can be an acute problem not only in major deformity surgery but also in less extensive fusion procedures. Controlled hypotension is among the most widely used techniques for reducing blood loss in various types of surgery including spine surgery.Aim of Study: The aim of the work was to evaluate the effect of preoperative clonidine vs. Atenolol on providing optimum surgical field in patients undergoing spine fusion surgery, and to minimize intraoperative blood loss and lastly for assessment of intraoperative surgeon satisfaction.Patients and Methods: This study was prospective double blinded randomized clinical trial, was conducted in Orthopedic Operative Rooms in Assiut University Hospitals on patients underwent spine fusion surgery. It was done from April 2016 till April 2017. Sixty patients (ASA I or II) were undergone elective spine fusion surgery were included in this study. Patients were randomly divided into three Groups I, II, III. Group 1 (control group), patients received oral placebo. Group II (Atenolol group), patients received oral Atenolol tablet 50mg, Group III (clonidine group), patients received oral clonidine tablet 100ug. These drugs were given to the patients 2hr before induction of anesthesia. The hemodynamic param-eters like Heart Rate (HR), Mean Arterial Blood Pressure (MAP), oxygen saturation (SPO2%) were checked intra and post operatively, intra-operative bleeding was measured, and the surgeon unaware of the group was asked to evaluate the quality of the operative field using the pre-defined Average Category Scale (ACS) at the end of surgical procedure.Results: Both intra and post-operative Heart Rate (HR), Mean Arterial Blood Pressure (MAP) were more reduced in Group II than in Group III than in Group I. Intraoperative blood loss and need for blood transfusion were less in Group II than in Group III than in Group I. The field was much better in Group II than in Group III than in Group I.Conclusion: This study concluded that both clonidine and atenolol were effective and safe, in terms of stable hemody-namic profile and reducing intraoperative bleeding; when given orally to patients as premedication in patients for spine surgeries under general anesthesia. However, out of the two drugs atenolol appeared to be better in terms of reduction of blood loss and providing good quality of surgical field when compared to clonidine.

A comparative study of effects of nebivolol and atenolol on blood pressure and lipid profile in patients of mild to moderate hypertension

Background: Beta blockers have been used in the treatment of hypertension, since last four decades and are widely accepted as the first-line treatment for hypertension. Nebivolol, a third generation β-blocker has highest β1 selectivity and is devoid of intrinsic sympathomimetic activity. Along with peripheral vasodilatation and nitric oxide (NO)-induced benefits such as antioxidant activity and reversal of endothelial dysfunction, nebivolol promotes better protection from cardiovascular events. The objective of the study was to compare the effects of atenolol and nebivolol on both blood pressure and lipid profile in patients of mild to moderate hypertension.Methods: This was a prospective, randomized, parallel, open labelled study. Patients were recruited from the medicine out-patient department (OPD) and cardiology OPD. A total of 100 patients were enrolled in the study. 50 patients were allocated to atenolol group and 50 patients to nebivolol group. BP and baseline investigations such as lipid profile were performed. Tests to determine lipid profile were performed on the first visit (Week 0) and at 24 weeks. Continuous variables between the two treatment groups were analyzed by unpaired t-test. Efficacy endpoints within the group were analyzed by using paired t-test.Results: All the lipid levels except HDL-C were increased with atenolol therapy. At 24 weeks, atenolol therapy led to increase in LDL-C, VLDL-C, TC and TG which was highly significant (p&lt;0.0001). HDL levels were decreased at 24 weeks which was also statistically highly significant (p&lt;0.0001). The mean values of lipids in nebivolol group at baseline and at 24 weeks. At 24 weeks, nebivolol therapy led to changes in LDL-C, VLDL-C, HDL-C, TC and TG which was not statistically significant (p&gt;0.05).Conclusions: From study it can be concluded that atenolol and nebivolol are equally effective in reducing BP but atenolol worsens lipid profile as compared to nebivolol.

Effect of nebivolol or atenolol vs. placebo on cardiovascular health in subjects with borderline blood pressure: the EVIDENCE study.

Pharmacotherapy to protect the arteries may be appropriate for individuals with high-normal blood pressure who are at risk for future cardiovascular disease (CVD). Nebivolol (NEB) in contrast to atenolol (ATE) may have a beneficial effect on endothelial function and may be more effective than ATE in preventing CVD. Sixty subjects with preHTN or borderline BP and abnormal small artery elasticity (SAE) underwent evaluation with 10 tests, including large and small artery elasticity, resting and treadmill exercise BP, carotid intimal-media thickness, retinal vascular photography, micro-albuminuria, electrocardiography, echocardiography, and plasma B-type natriuretic peptide level. Each test scored as normal (0), borderline (1), or abnormal (2), and the total disease score (DS) was calculated by adding the test scores. Subjects were randomized double-blind to placebo (PLAC, n = 22), NEB 5/10 mg/day (n = 20),or ATE 25/50 mg/day (n = 18) once daily for 9 months. After 9 months,in the group receiving NEB the mean (standard deviation) DS decreased from baseline 4.3 (2.6) to 2.8 (2.4) (P < 0.007), with ATE from 5.4 (2.5) to 3.5 (1.9) (P = 0.0006), and with PLAC from 5.2 (3.0) to 4.5 (2.6) (P = 0.18). SAE increased in the NEB group from 6.0 (2.2) to 8.4 (3.4) ml/mmHg × 100 (P = 0.0001), whereas there was no significant change in the ATE and PLAC groups. Thus, nebivolol improves small artery function more than atenolol in asymptomatic subjects with preHTN or borderline BP, despite their similar BP-lowering effect.

Prospective, randomized double blind comparative study of safety and efficacy of carvedilol versus atenolol in patients of mild to moderate hypertension

Background: Carvedilol is a new cardiovascular compound with the combined pharmacologic properties of nonselective ß-blockade and vasodilation. The Aim of the study was to compare the safety and antihypertensive efficacy of 25mg Carvedilol once daily with 50mg atenolol once daily in patients with mild to moderate essential hypertension.Methods: This was a single center study conducted in Rangaraya Medical College, Kakinada. 80 eligible patients with mild to moderate hypertension were randomized to receive 25mg Carvedilol once daily (40 patients) or 50mg atenolol (40 patients) in a double-blind 12-week treatment phase. At each visit 0, 4, 8 and 12 weeks of treatment, sitting Blood Pressure (BP) and heart rate were measured. The effect on BP reduction within the group is compared by paired “t”test and the effect on reduction of BP between two study groups compared by unpaired “t”test.Results: After 12 weeks of treatment, the mean reduction of SBP (Systolic Blood Pressure) with carvedilol is 22.33±8.31mmHg with no Significant difference (p &gt;0.05) compared to atenolol group mean reduction in SBP of 21.37±10mm Hg. The mean reduction in DBP (Diastolic Blood Pressure) after completion of the study in carvedilol group is 6.75±4.82mm Hg with no Significant difference (p &gt;0.05) compared to atenolol group mean reduction in DBP of 8.55±5.25mm Hg. No significant difference seen in the efficacy parameters of both the drugs. The incidence of adverse effects such as bradycardia, headache, nausea, vomiting, hypotension and rash is less with carvedilol.Conclusions: In patients with mild to moderate hypertension, there was no statistically significant difference between efficacy of carvedilol or atenolol with regard to the degree of reduction in BP or the percentage of patients achieving a response to therapy but carvedilol showed a better safety profile when compared to atenolol.

Cardiac contractility: Correction strategies applied to telemetry data from a HESI-sponsored consortium

IntroductionQT has a long history of heart rate (HR) correction but limited investigations have been undertaken to assess the impact of cardiovascular parameters on left ventricular (LV) contractility in drug safety testing. Cardiac contractility is affected by preload (Cyon-Frank-Starling law), afterload (Anrep effect) and HR (Bowditch effect). We evaluated multi-parameter correction methods to help with dP/dtmax interpretation. MethodologyModeling was undertaken using data from dogs in single or double 4×4 Latin square studies. Correction models (16 fitting formulas×2 modeling approaches (universal and individualized)×2 correction approaches (linear or proportional)) were evaluated. 3D/2D cloud analysis of the beat-to-beat data for the control, pimobendan, and either itraconazole or atenolol groups were used to evaluate correlations between parameters and derive an optimal correction method. ResultsCardiac contractility (i.e., dP/dtmax) was best correlated to HR and systolic LV pressure with a correlation coefficient of 0.8. In decreasing order, dP/dtmin, mean arterial blood pressure (BP), systolic BP, diastolic BP, arterial pulse pressure and LV end diastolic pressure (LVEDP) showed a reduced correlation to dP/dtmax. Subject-specific models improved the correction by up to 14% when compared to universal correction models. The non-linear correction model was superior to the linear model. DiscussionResults suggest that the optimal correction formula for dP/dtmax would be subject-specific, non-linear and would include HR and LV systolic pressure. Correcting contractility for HR and systolic LV pressure may enhance data interpretation in non-clinical drug safety assessments. Similar correction methods could be evaluated for other species used in safety pharmacology.