Β-adrenergic Blocking Drugs Research Articles

Anti-tumor effects of propranolol: Adjuvant activity on a transplanted murine breast cancer model

Propranolol (Pro), a non-specific β-adrenergic blocking drug, competitively prevents the binding of catecholamines to receptors and suppresses cancer cells. The anti-tumor activity of propranolol has been proved in different kinds of cancers. In this study, we assessed the adjuvant activity of propranolol combined with a tumor vaccine model on the immunological parameters of breast tumor-bearing mice. Breast tumor pieces were implanted into the flank of inbred BALB/C female mice from stock mice. Tumor-bearing mice were treated with tumor antigen lysate vaccine and propranolol/Vaccine (Pro/Vac) combination (as treatment groups), propranolol and PBS (as control groups) for 5 consecutive days, every 12 h. Moreover, all experimental groups received vaccine for three times with one-week interval via s.c injection. After immunization courses, spleens of tumor-bearing mice were removed and dissected, cell suspension was stimulated in vitro, and the cytokine levels in supernatant of splenocytes were measured via commercial ELISA kits. Compared with the vaccine group, immunization with tumor lysate in combination with propranolol significantly increased IL-2, IL-4, IL-12, IL-17, and IFN-γ cytokines. Considering the suppression of tumor growth, propranolol seems to be a potent immunomodulator capable of inducing cellular immune responses against breast cancer.

Lowering blood pressure with β-blockers in peripheral artery disease: the importance of comorbidity

Lowering blood pressure with β-blockers in peripheral artery disease: the importance of comorbidity

Preoperative stress testing in high-risk vascular surgery and its association with gender

Despite significant improvement in anesthetic and surgical techniques, the incidence of perioperative myocardial infarction (PMI) and all-cause mortality from any cardiac event during high-risk vascular surgery (abdominal aortic or infrainguinal revascularization procedures) remains high. In addition, there are significant health care costs associated with the management of PMI. The aim of this analysis was to investigate the utility of routine preoperative myocardial stress testing prior to high-risk vascular surgery and the interventions performed based on the results of the testing. The outcome after surgery, based on sex of the patients, was also examined. A retrospective analysis was performed on consecutive adult patients who had a positive dipyridamole-thallium stress test prior to high-risk vascular surgery in a university hospital (tertiary care center) between July 2001 and August 2004. The patients' preoperative demographic characteristics, perioperative record, and postoperative course in the hospital were analyzed. Combined major adverse outcome was defined as any incidence of MI, congestive heart failure, arrhythmias, renal failure, or death. Of a total of 503 patients, 160 had a positive stress test prior to high-risk vascular surgery (111 men, 49 women; mean [SD] age, 68 [11] and 70 [12] years, respectively). Men with a positive stress test who had either coronary intervention or perioperative β-blockade prior to surgery had a significant decrease in the incidence of combined major adverse outcomes (P = 0.02). Conversely, women did not have a significant improvement in outcome with either of the preoperative strategies. Using logistic regression, only age and conservative management in men were found to be predictors of adverse outcomes. In this small retrospective study, men with positive stress tests had fewer adverse events with either preoperative coronary revascularization or perioperative administration of β-adrenergic blocking drugs, compared with men who received no intervention. There were no significant differences in adverse outcomes between women with positive stress tests who received either treatment compared with those who did not receive any treatment.

Evolving Concepts Concerning Cardiac β-Adrenoceptor Function in Heart Failure

This review describes the clinical application of β-adrenergic blocking drugs over time in patients with congestive heart failure. The different pharmacological properties of these drugs in relation to clinical outcomes raises questions as to their optimal desirable profile based on studies showing the undesirable effects of excessive β(2)-AR activation. The rationale for the use of selective β(2)-AR antagonists in heart failure is discussed.

Propranolol suppresses angiogenesis in vitro: Inhibition of proliferation, migration, and differentiation of endothelial cells

Propranolol, a non-selective β-adrenergic blocking drug, was recently reported to control the growth of hemangiomas, the most common vascular tumor of infancy. However, the mechanisms involved in this effect remain unknown. Here, we demonstrate that propranolol dose-dependently inhibited growth factor-induced proliferation of cultured human umbilical vein endothelial cells (HUVECs) through a G 0/G 1 phase cell cycle arrest. This was correlated to decreased cyclin D1, cyclin D3, and cyclin-dependent kinase CDK6 protein levels, while increases in the CDK inhibitors p15 INK4B, p21 WAF1/Cip1 and p27 Kip1 were observed. Chemotactic motility and differentiation of HUVECs into capillary-like tubular structures in Matrigel were also inhibited by propranolol. Furthermore, inhibition by propranolol of vascular endothelial growth factor (VEGF)-induced tyrosine phosphorylation of VEGF receptor-2 lead to inhibition of downstream signaling such as the activation of the extracellular signal-regulated kinase-1/2 and the secretion of the extracellular matrix degrading enzyme MMP-2. Taken together, these results demonstrate that propranolol interferes with several essential steps of neovascularization and opens up novel therapeutic opportunities for the use of β-blockers in the treatment of angiogenesis-dependent human diseases.

Conformational structure of propranolol: A β-adrenergic blocking drug studied by NMR and PCILO methods

The conformational structure of propranolol, a β-adrenergic blocking drug, has been investigated by pcilo calculations and 270-MHz proton nuclear magnetic resonance in D2O solution. The molecules coexist in at least two conformational states in solution with a low energy barrier. Both preferred conformations have extended structures which allow a three-point drug-receptor binding involving the aromatic moiety, the β-hydroxyl group, and -NH+2 groups of propranolol. The previously postulated “rigid” bicyclic structure does not exist to an appreciable extent in D2O solution.

The Anesthesiology Community's Approach to Opioid- and Anesthetic-abusing Personnel

The Anesthesiology Community's Approach to Opioid- and Anesthetic-abusing Personnel

Thyroid Hormone Treatment to Mend a Broken Heart

Thyroid Hormone Treatment to Mend a Broken Heart

Sex-Related Differences in Outcome After High-Risk Vascular Surgery After the Administration of β-Adrenergic–Blocking Drugs

Beta-adrenergic-blocking medications may have a cardioprotective effect after high-risk vascular surgery. This effect has been shown primarily in men and has not been independently shown in women. Retrospective data were collected from vascular surgery (primarily infrainguinal) patients. Adverse outcome was defined as myocardial infarction, new-onset congestive heart failure (CHF), significant arrhythmia, renal failure, or death. The incidence of adverse outcomes was compared independently for both men and women based on the administration of perioperative beta-blockade. Analysis was performed for the whole population and for the subset of patients who were not on preoperative beta-blockers (beta-blocker naïve). Risk-stratified analysis was used to determine which group received any effect from beta-blockade. Logistic regression was performed to determine the independent effect of perioperative beta-blockade in both sexes. There were 594 men and 366 women. The incidence of adverse outcomes was lower when beta-blockers were administered in men (12.6% v 18.9%, p = 0.04) but not in women (17.8% v 13.7%, p = 0.37). Among beta-blocker-naïve subjects, men had significant reductions in myocardial infarction and renal failure, whereas women did not have a reduction in the incidence of any outcome. After risk-stratification, the high-risk women who received beta-blockade had a statistically worse outcome (36.8% v 5.9%, p = 0.02) because of an increased incidence of CHF. By logistic regression, beta-blockade improved outcomes in men but not women. In this retrospective analysis, women did not benefit from perioperative beta-blockade. Women at high risk appeared to have a worse outcome because of a higher incidence of CHF.

Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

EXCRETION OF ACEBUTOLOL AND ITS MAJOR METABOLITE DIACETOLOL INTO INFANT BLOOD CIRCULATION AND THE BREAST MILK

Acebutolol (AC) is a chiral β-adrenergic blocking drug, which is useful clinically as the racemate in treating hypertension and is metabolized to an equipotent chiral metabolite, diacetolol (DC). In this paper we report a case of a 32 year old woman who was receiving AC during her pregnancy and lactating time for management of hypertension. The maternal plasma level and breast milk as well as cord blood collected to see whether the drug is transferred to the fetus through the mother stereoselectively. A stereospecific high-performance liquid chromatographic (HPLC) assay was used to measure the enantiomeric concentrations of AC and DC. AC and DC enantiomers are stereoselectively excreted into the milk, although the concentrations of DC enantiomers were higher than those of AC. AC concentrations were very low in both cord artery and vein samples four hours after taking the drug however, the stereoselective concentrations of metabolite, DC, was found in these samples. In conclusion, AC and DC enantiomers are excreted in human breast milk in concentrations much higher than that in maternal plasma. Furthermore, DC was found in the infant’s plasma indicating that accumulation of metabolite did occur in this infant.

Beta-adrenergic blocking drugs as antifibrillatory agents.

Beta-Adrenergic blockade is associated with a significant reduction in mortality in most patients with structural heart disease. Clinical trial data involving patients after myocardial infarction or with congestive heart failure demonstrate that a reduction in sudden death accounts for much of the observed mortality reduction. Beta-adrenergic blockade inhibits the proarrhythmic effects of both neural and humoral sympathetic stimulation and inhibits the vagal withdrawal that accompanies ischemia. Although it does not have a dramatic effect on spontaneous ectopy or inducible monomorphic ventricular tachycardia, experimental and clinical data suggest that it inhibits the development of ventricular fibrillation by several mechanisms.

Treatment of Persistent Tachycardia with Dexmedetomidine During Off-Pump Cardiac Surgery

Treatment of Persistent Tachycardia with Dexmedetomidine During Off-Pump Cardiac Surgery

Response to Electroconvulsive Therapy in a Quadriplegic Patient

Response to Electroconvulsive Therapy in a Quadriplegic Patient

The influence of beta-adrenergic blocking drugs on morbidity and mortality in heart failure.

The influence of beta-adrenergic blocking drugs on morbidity and mortality in heart failure.

Clinical Efficacy of Carvedilol in Patients with Moderate to Severe Congestive Heart Failure

Background：Clinical trials have shown that β-adrenergic blocking drugs are effective and well tolerated in patients with mild to moderate congestive heart failure. Carvedilol is a mild β1-selective adrenergic blocking agent with vasodilating properties due to α blocker and antioxidant and anti-proliferative properties. This study assessed the efficacy and safety of carvedilol in patients with moderate to severe congestive heart failure caused by idiopathic dilated cardiomyopathy. Methods：We enrolled 27 patients with moderate to severe congestive heart failure with a left ventricular ejection fraction of 35% by MUGA scan. Each patient was randomly assigned to either control (n＝9 or carvedilol (n＝18, target dose 25 mg bid for 6 months while background therapy with digoxin, diuretics, and ACE inhibitor remained constant. Results：Compared to the control group, patients in the carvedilol group showed significant increase of left ventricular ejection fraction (p<0.05. In addition, patients in the carvedilol group had a tendency to show a decrease in left ventricular end-diastolic dimension and heart rate. Also, the carvedilol group had a greater frequency of symptomatic improvement than the control group. There was neither serious side effects nor hospitalization. Conclusion： These finding indicate that carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and ACE inhibitor without serious side effects. (Korean Circulation J 1998;28(4 :523-531

Effects of serotonin, adrenaline and other vasoactive drugs on the branchial blood vessels of the Antarctic fish Pagothenia borchgrevinki

Myography and an isolated, perfused gill arch preparation were used to investigate the actions of drugs on the gill vasculature of an Antarctic teleost fish, Pagothenia borchgrevinki. Serotonin produced a dose-dependent vasoconstriction of the afferant branchial arteries, the gill arch and the efferent branchial arteries, and was the most potent vasoconstrictor tested. Acetylcholine, at concentrations exceeding 1 × 10-6M, vasoconstricted the gill arch, but had a negligible effect on the branchial arteries. The responses to adrenaline, with and without the β-adrenergic blocking drug, sotalol and the effects of the β-adrenergic agonist drug isoprenaline indicated the presence of both α-adrenergic and β-adrenergic receptors in the gill vasculature, with the vasoconstrictory action of the former predominating in the efferent vasculature. Angiotensin II was without effect in either preparation. The results are a further demonstration of the dominance of vasoconstrictory responses in the control of gill cular resistance in P. borchgrevinki: which has been associated previously with the sub-zero temperatures at which the animals are found.

Effects of Beta Blockers on Symptoms and Functional Capacity in Heart Failure

Beta-adrenergic-blocking drugs ameliorate the progression of disease that usually characterizes heart failure. All of the larger multicenter studies have demonstrated reductions in morbidity, manifested by a reduction in the number of hospitalizations and/or listing for cardiac transplantation, whereas studies with carvedilol have also reported a significant reduction in mortality. The influence of β-adrenergic blocking drugs on the symptomatic and functional status of patients with heart failure has been more difficult to establish. Almost all trials have reported an improvement in New York Heart Association (NYHA) functional class, with few patients experiencing functional deterioration. Improvement in symptom score was reported in the Metoprolol in Dilated Cardiomyopathy (MDC) trial for patients treated with metoprolol. In patients from the US Carvedilol Heart Failure Trials Program who had heart failure from ischemic and nonischemic etiologies, both patients and physicians reported more improvement and less deterioration in an assessment of global status. More formal instruments to assess quality of life, such as the specific activity scale in the Australia-New Zealand trial of carvedilol (that recruited 30% of patients who had improved to NYHA stage I) and the Minnesota Quality of Life questionnaire, did not seem sensitive to the clinical benefits observed in these trials. Serial exercise testing similarly does not seem sensitive to the beneficial influence of β-adrenergic blocking drugs on disease progression, at least in relatively short-term studies.

Comparison of two extraction methods for determination of propranolol and furosemide in human plasma by mixed-mode chromatography

An isocratic high performance liquid chromatographic method is described for the determination of the β-adrenergic blocking drug, propranolol, and the diuretic, furosemide, in human plasma. The two compounds and the internal standard were extracted from plasma using a two-step extraction technique. Propranolol and pindolol (internal standard) were first extracted from alkaline plasma into diethyl ether; this was followed by extraction of furosemide into acidified ether: hexane (65:35). The two extracts were then combined and evaporated under nitrogen, and the reconstituted residues were analysed on a C18/SCX reversed-phase/cation exchange column with a mobile phase of acetonitrile: 0.1 M sodium acetate pH 4 (33:67). The drugs and the internal standard were detected by UV absorption at 230 nm. The drugs were also extracted from plasma by a column-switching technique utilizing a ten-port valve. The drug compounds were retained on a C18 pre-column. A comparison of RSD for within-batch (intra-assay) and between-batch (inter-assay) runs for both methods was carried out, the liquid/liquid extraction method giving better recovery values. The calibration graphs were linear from 25–300 ng ml −1 for furosemide and 50–400 ng ml −1 for propranolol. Recovery values were > 90.0% by liquid/liquid extraction and > 76.0% by column switching.

Hemodynamic effects and safety of sotalol in the prevention of supraventricular arrhythmias after coronary artery bypass surgery

Sotalol is a β-adrenergic blocking drug with the additional property of lengthening the cardiac action potential. These electrophysiologic properties render the drug attractive for use in the prevention of postoperative supraventricular arrhythmias (SVA), and previous studies have suggested that it was indeed effective. The hemodynamic response to sotalol and its safety early after coronary artery bypass graft (CABG) surgery were therefore studied. Forty-two patients undergoing CABG were randomly assigned either to receive sotalol to prevent postoperative SVA (25 patients) or to serve as controls (17 patients). Sotalol was started 6 hours after surgery if patients had a cardiac index >2.8 L/min/m 2 with a pulmonary capillary wedge pressure <15 mmHg, and if they had no contraindications to the use of β-blockers. The drug was given as a loading infusion of 1 mg/kg over 2 hours, followed by a maintenance infusion of 0.15 mg/kg/h for 24 hours. Three hours later, patients received the first oral dose of 80 mg to be repeated every 8 or 12 hours. Adverse effects necessitating discontinuation of the drug (bradycardia <50 beats/min, systolic blood pressure <90 mmHg, or cardiac index <2.2 L/min/m 2) occurred in six patients (24%) and were mainly related to the loading infusion. The hemodynamic data for patients who completed the study were characterized by a significant fall of the cardiac index caused by a lower heart rate without significant change of the stroke volume index. The incidence of supraventricular arrhythmias was not significantly different in the two groups ( 3 19 in the sotalol group, 5 17 in the control group). In conclusion, at the dosage used, sotalol was associated with a high incidence of adverse reactions, precluding the enrollment of enough patients to assess a possible efficacy in the prevention of postoperative SVA. Bradycardia, accompanied by a significant decrease of cardiac index, was found. Therefore, it is concluded that this drug should be used very cautiously after coronary artery surgery.