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We sought to investigate whether the β-adrenergic receptors play a pivotal role in sex-related differences in arterial blood pressure (BP) regulation during isometric exercise. Sixteen volunteers (8 women) performed 2 min of ischemic isometric handgrip exercise (IHE) and 2 min of postexercise circulatory occlusion (PECO). Heart rate (HR) and beat-to-beat arterial BP were continuously measured. Beat-to-beat estimates of stroke volume (ModelFlow) were obtained and matched with HR to calculate cardiac output (Q̇) and total peripheral resistance (TPR). Two trials were randomly conducted between placebo and nonselective β-adrenergic blockade (40 mg propranolol). Under the placebo condition, the magnitude of the BP response in IHE was lower in women compared with men. During PECO, the BP remained elevated and the sex differences persisted. The β-blockade attenuated the BP response during IHE in men (∆57 ± 4 vs. ∆45 ± 7 mmHg, P = 0.025) due to a reduction in Q̇ (∆3.7 ± 0.5 vs. ∆1.8 ± 0.2 L/min, P = 0.012) while TPR was not affected. In women, however, the BP response during IHE was unchanged (∆27 ± 3 vs. ∆28 ± 3 mmHg, P = 0.889), despite attenuated Q̇ (∆2.7 ± 0.4 vs. ∆1.3 ± 0.2 L/min, P = 0.012). These responses were mediated by a robust increase in TPR under β-blockade (∆−0.2 ± 0.4 vs. ∆2.2 ± 0.7 mmHg·L−1·min, P = 0.012). These findings demonstrate that the sex differences in arterial BP regulation during ischemic IHE are mediated by β-adrenergic receptors. NEW & NOTEWORTHY We found that the blood pressure response during isometric exercise in women is mediated by increases in cardiac output, whereas in men it is mediated by increases in both cardiac output and total peripheral resistance. In addition, women showed a robust increase in total peripheral resistance under β-blockade during isometric exercise and muscle metaboreflex activation. These findings demonstrate that sex differences in blood pressure regulation during isometric exercise are mediated by β-adrenergic receptors.

BackgroundThere is a significant postoperative mortality risk in patients subjected to surgery for hip fractures. Adrenergic hyperactivity induced by trauma and subsequent surgery is thought to be an important contributor. By downregulating the effect of circulating catecholamines the increased risk of postoperative mortality may be reduced. The aim of the current study is to assess the association between regular β-blocker therapy and postoperative mortality.MethodsThis cohort study used the prospectively collected Swedish National Quality Registry for hip fractures to identify all patients over 40 years of age subjected to surgery for hip fractures between 2013 and 2017 in Örebro County, Sweden. Patients with ongoing β-blocker therapy at the time of surgery were allocated to the β-blocker-positive cohort. The primary outcome of interest was 90-day postoperative mortality. Risk factors for 90-day mortality were evaluated using Poisson regression analysis.ResultsA total of 2443 patients were included in this cohort of whom 900 (36.8%) had ongoing β-blocker therapy before surgery. The β-blocker positive group was significantly older, less fit for surgery based on their American Society of Anesthesiologists classification and had a higher prevalence of comorbidities. A significant risk reduction in 90-day mortality was detected in patients receiving β-blockers (adjusted incidence rate ratio=0.82, 95% CI 0.68 to 0.98, p=0.03).Conclusionsβ-blocker therapy is associated with a significant reduction in 90-day postoperative mortality after hip fracture surgery. Further investigation into this finding is warranted.Level of evidenceTherapeutic study, level III; prognostic study, level II.

Intense exercise decreases the cerebral metabolic ratio of oxygen to carbohydrates [O(2)/(glucose + (1/2)lactate)], but whether this ratio is influenced by adrenergic stimulation is not known. In eight males, incremental cycle ergometry increased arterial lactate to 15.3 +/- 4.2 mm (mean +/- s.d.) and the arterial-jugular venous (a-v) difference from -0.02 +/- 0.03 mm at rest to 1.0 +/- 0.5 mm (P < 0.05). The a-v difference for glucose increased from 0.7 +/- 0.3 to 0.9 +/- 0.1 mm (P < 0.05) at exhaustion and the cerebral metabolic ratio decreased from 5.5 +/- 1.4 to 3.0 +/- 0.3 (P < 0.01). Administration of a non-selective beta-adrenergic (beta(1) + beta(2)) receptor antagonist (propranolol) reduced heart rate (69 +/- 8 to 58 +/- 6 beats min(-1)) and exercise capacity (239 +/- 42 to 209 +/- 31 W; P < 0.05) with arterial lactate reaching 9.4 +/- 3.6 mm. During exercise with propranolol, the increase in a-v lactate difference (to 0.5 +/- 0.5 mm; P < 0.05) was attenuated and the a-v glucose difference and the cerebral metabolic ratio remained at levels similar to those at rest. Together with the previous finding that the cerebral metabolic ratio is unaffected during exercise with administration of the beta(1)-receptor antagonist metropolol, the present results suggest that the cerebral metabolic ratio decreases in response to a beta(2)-receptor mechanism.

Objective: An immunomodulatory effect of epinephrine has been reported that is supposed to be mediated via β-adrenergic receptors. The effect of epinephrine and/or β-adrenergic blockade on cellular immune functions during systemic inflammation has not yet been investigated. Methods: Male NMRI mice were treated with either an infusion of epinephrine (0.05 mg/kg/h i.p.), administration of the nonselective β-adrenoceptor antagonist propranolol (0.5 mg/kg s.c.), or a combination of epinephrine and propranolol after induction of a polymicrobial sepsis by cecal ligation and puncture. Forty-eight hours thereafter survival and cellular immune functions (splenocyte proliferation, splenocyte apoptosis and cytokine release, distribution of leukocyte subsets) were determined. Results: Infusion of epinephrine did not affect lethality of septic mice but induced alterations of splenocyte apoptosis, splenocyte proliferation and IL-2 release and was associated with profound changes of circulating immune cell subpopulations. Treatment with propranolol augmented the epinephrine-induced increase of splenocyte apoptosis, did not affect the decrease of splenocyte proliferation and IL-2 release, augmented the release of IL-6 and antagonized the mobilization of natural killer cells observed in epinephrine-treated animals. Furthermore, these immunologic alterations were accompanied by a significant increase of sepsis-induced mortality. Coadministration of propranolol and epinephrine augmented the propranolol-induced changes of splenocyte apoptosis and IL-6 release and was associated with the highest mortality of septic mice. Conclusion: Epinephrine infusion modulated cellular immune functions during systemic inflammation without an impact on survival. A pharmacologic β-adrenergic blockade partly augmented the epinephrine-induced immune alterations and was associated with a pronounced increase of mortality. This effect was further augmented by a combination of epinephrine infusion and β-adrenergic blockade. These data indicate that adrenergic mechanisms modulate cellular immune functions and survival during sepsis, with these effects being mediated via α- and β-adrenergic pathways.

Background Although β-blockers (BBs) have been shown to improve cardiac function, there is individual and ethnic variation in BB clinical response. We examined the effects of BBs on left ventricular remodeling among African Americans (AAs), Hispanics, and Caucasians with systolic heart failure. Hypothesis There is ethnic variability in the effects of BBs on cardiac remodeling. Methods There were 185 AAs, 159 Hispanics, and 74 Caucasians selected with ejection fraction ≤40% from any etiology. Change in left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimensions (LVEDD), and degree of mitral regurgitation (MR) in response to 1 year of BBs was evaluated retrospectively. Results Overall, there was a significant improvement in LVEF, LVEDD, and degree of MR in AAs and Caucasians after 1 year of BBs (P < 0.001 vs baseline). Compared with other races, Hispanics (%) had no significant improvement in LVEDD and degree of MR, and had fewer patients with reverse remodeling: LVEF (42.77%), LVEDD (5.03%), and MR (16.35%). In multivariable analysis, Hispanic and AA race were important predictors of LVEF and LVEDD (P < 0.01) but not MR response. Conclusions Although most patients demonstrated improvement of LVEF, there seems to be ethnic variability in the effects of BBs on cardiac remodeling. Degree of MR and LVEDD failed to show improvement among Hispanics.

purpose: To review the current data regarding the use of β-adrenergic blockers for the treatment of congestive heart failure. material and methods: Relevant studies published between 1975 and 1991 were reviewed. Key data from each study were extracted. The significance of conclusions reached by each author(s) was identified. results: β-Adrenergic blockade, although still considered an investigational therapy for the treatment of congestive heart failure, has been proven in several studies to improve ventricular function, including myocardial contractility and relaxation. In addition, since β-blockade up-regulates myocardial β-receptors, the myocardium becomes more responsive to graded doses of β-agonists. Speculation regarding the possible mechanisms of these effects is presented. In addition, since β-blockers have been shown to reduce neurohormonal activation, they may have a beneficial effect on survival. Although small pilot studies or subgroup analysis of larger studies suggest β-blockade therapy improves survival in heart failure, this has yet to be proven. Large prospective trials are warranted to study this issue. conclusions: As current data suggest, β-blockers improve ventricular function and reduce neurohormonal activation in heart failure. β-blockers should be considered as adjunctive therapy in patients with congestive heart failure. In addition, future studies are warranted to better elucidate their effects on ventricular function and survival.

We tested the hypotheses that nonselective beta-adrenergic blockade does not cause absolute hypoglycemia unawareness but shifts the glycemic thresholds for symptoms to lower plasma glucose concentrations and that neither neuroglycopenic symptoms nor cognitive impairments during hypoglycemia are altered by beta-adrenergic blockade. To do so, we applied the euglycemic and stepped hypoglycemic clamp techniques to patients with moderately controlled insulin-dependent diabetes mellitus (IDDM) in the absence (n = 8) and presence (n = 9) of the nonselective beta-adrenergic antagonist propranolol. Compared with the corresponding euglycemic clamps, total symptom scores first increased at the 4.4-mM plasma glucose step (a higher level than that of 2.8 mM in nondiabetic subjects studied previously) in the absence of propranolol. Beta-adrenergic blockade did not produce absolute hypoglycemia unawareness. Indeed, at the frankly hypoglycemic step of 2.8 mM, total symptom scores tended to be higher in the presence than in the absence of propranolol. This was largely the result of greater (P less than 0.01) perception of diaphoresis. However, symptom scores did not increase until the 3.3-mM plasma glucose step during beta-adrenergic blockade. The perception of hunger, and perhaps that of tremulousness, was reduced by propranolol at the higher glucose steps. Neuroglycopenic symptoms were not reduced by propranolol. The cognitive function of memory, but not that of attention, was impaired, also starting at the 4.4-mM glucose step. This was not impaired further by propranolol. Thus, we formed the following conclusions. 1) Nonselective beta-adrenergic blockade does not cause absolute hypoglycemia unawareness but shifts the glycemic thresholds for symptoms to lower plasma glucose concentrations in patients with IDDM. 2) Beta-adrenergic blockade does not reduce neuroglycopenic symptoms, and it does not further impair cognitive function during hypoglycemia in IDDM patients.

The effect of β-adrenergic blockade on the dynamic response characteristics of oxygen uptake\(\left( {\dot VO_2 } \right)\) was examined in seven healthy men. Cycle ergometer exercise consisted of a pseudorandom binary sequence (PRBS) with 15 units per sequence, each unit lasting 15 s, for a total period of 225 s. Work rate was either 25 W or 125 W. Six identical sequences were performed continuously in a single exercise test. Each subject was studied on three occasions after 48 h treatment of placebo (CON); a nonselective β-blocker, propranolol (PROP); and a β1-selective blocker, metoprolol (MET).\(\dot V_{O_2 } \) was measured breath-by-breath. The data were analyzed in the frequency domain by Fourier analysis to yield amplitude and phase shift coefficients for the relationship between the input work rate and output\(\dot V_{O_2 } \). Time domain analysis was performed on the cross-correlational analysis of\(\dot V_{O_2 } \) (output) · work rate (input) to determine the total lag time. The amplitude of the\(\dot V_{O_2 } \) · W−1 relationship was lower (P

Aim To study the efficacy and tolerability of β-blockade in elderly patients with heart failure in the MERIT-HF study. Methods and results Cox proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Risk reduction was defined as (1-HR). In patients ⩾65 years total mortality was reduced by 37% (95% CI 17% to 52%; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.0008\) \end{document}), sudden death by 43% (95% CI 17% to 61%; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.0032\) \end{document}), and death from worsening heart failure by 61% (95% CI 32% to 77%; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.0005\) \end{document}). Hospitalisations for worsening heart failure was reduced by 36% \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((p=0.0006)\) \end{document}. Elderly patients with severe heart failure (NYHA class III/IV with ejection fraction \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({

Emotional arousal has been shown to enhance memory, an effect that is blocked by propranolol suggesting that the noradrenergic system is important in the mechanism action. Because PTSD has as prominent features heightened arousal and distressing memories, the current study was undertaken to examine whether PTSD subjects differed from controls in emotional enhancement of memory. Seventeen subjects with PTSD and 21 controls received either placebo or 40 mg of propranolol prior to exposure to either an emotionally arousing or emotionally neutral, narrated slide story. Recall, measured 1 wk later, for the arousing story was enhanced and this effect was reduced by propranolol. PTSD and control subjects did not differ in the acquisition and retention of memories under emotionally arousing or emotionally neutral conditions, nor were differential effects of propranolol observed between the two groups.

PURPOSE The authors compare the major components of energy balance--dietary food intake, resting metabolic rate, and physical energy expenditure--in patients receiving beta-blocking medications and healthy controls. METHODS The authors recruited subjects who were receiving beta-blocking agents (n = 22) from local hospitals and clinics. Twenty-two healthy controls were matched to each patient based on age, weight, and gender. Resting metabolic rates were determined using indirect calorimetry. Three-day dietary intakes and physical activity assessments were analyzed. RESULTS There were no between-group differences in calories ingested or self-reported physical activity patterns. However, resting metabolic rates were lower in the beta-blocked subjects (beta-blocked = 1,541 +/- 464 kcals/day; controls = 1,817 +/- 426 kcals/day; P < 0.05). CONCLUSIONS beta-adrenergic blockade causes a reduction in resting metabolic rate. Therefore, beta-blocked individuals should increase physical activity, decrease dietary intake, or both to maintain daily energy balance and prevent weight gain that accompanies a reduction in metabolic rate.

The mechanism of vasodepressor reaction induced by head-up tilt test in patients with vasodepressor syncope is not clearly understood. We hypothesized that an abnormal alteration of β-adrenergic transmission could be involved in these patients. We measured plasma catecholamine concentration during tilt and density of β-adrenoceptors and tested the effects of β-adrenergic blockers in the prevention of the vasodepressor reaction in patients with vasodepressor syncope. Ten patients had reproducibly induced vasodepressor syncope (mean 3.1 ± 0.3 episodes in each patient) with head-up tilt (80 degrees) for 10 minutes with isoproterenol infusion (1 to 3 μg/min). Syncope occurred at 6.3 ± 1.7 minutes during tilt with isoproterenol infusion. The plasma norepinephrine concentration before administration of β-blocker was significantly elevated during tilt compared to the supine position (0.347 ± 0.079 ng/ml in supine position with isoproterenol vs 0.468 ± 0.082 ng/ml at 3 minutes of tilt, p < 0.001, andvs 0.503 ± 0.106 ng/ml at the onset of vasodepressor reaction, p < 0.005; n = 8). Plasma norepinephrine after administration of the selective β1-adrenergic blocker metoprolol (40 mg/day) was similarly elevated (0.282 ± 0.071 ng/ml in supine position with isoproterenol vs 0.390 ± 0.078 ng/ml at 3 minutes of tilt, p < 0.05, n = 6; and vs 0.547 ± 0.152 ng/ml at the onset of vasodepressor reaction, p < 0.001, n = 3). Plasma norepinephrine after administration of the nonselective β-blocker propranolol (30 mg/day) was not significantly elevated (0.254 ± 0.063 ng/ml in supine position with isoproterenol vs 0.339 ± 0.081 ng/ml at 3 minutes of tilt, p not significant; and vs 0.343 ± 0.079 ng/ml at 10 minutes of tilt, p not significant, n = 6). Metoprolol prevented vasodepressor syncope in 5 of 10 patients; propranolol prevented syncope in all 10 patients (p < 0.05). Heart rate after administration of propranolol did not increase in either the supine position with isoproterenol or during tilt compared to control tilt and tilt after administration of metoprolol. We abserved no significant differences in the number and afrinity of β-adrenoceptors between five patients with vasodepressor syncope and tive age-matched normal subjects. We conclude that propranolol is far more useful for the prevention of vasodepressor syncope than metoprolol. Our data suggest that β2-adrenergic transmission may play an important role in the induction of vasodepressor reaction in patients with vasodepressor syncope.

In 107 patients with acute myocardial infarction, the incidence of ventricular arrhythmias during the acute phase of thrombolysis was examined by means of Holter monitoring. In patients with a patent infarct-related artery as assessed angiographically at 90 minutes, the occurrence of accelerated idioventricular rhythms was noted significantly more frequently than in patients with a permanent occluded vessel. This arrhythmia peaked in the first 180 minutes after the start of thrombolysis. In addition, single ventricular premature beats and runs of ventricular tachycardia were also more common in patients with successful reperfusion. The effects of acute intravenous administration of β-blockers were examined in 66 patients without contraindications to this therapeutic approach. There were no differences in the occurrence of any type of rhythm disorders in patients with ( n = 43) or without β-blockade ( n = 23). Thus ventricular arrhythmias particularly accelerated idioventricular rhythms, and single ventricular premature beats occur more frequently in patients with a patent infarct artery within the first 24 hours after thrombolysis. Acute intravenous β-blockade does not appear to exert significant antiarrhythmic effects during this period.

Phaeochromocytomas of the heart are very rare. This report describes the case of a 69 year old woman presenting with persistent hypertension and a left atrial phaeochromocytoma diagnosed by 131I-metaiodobenzylguanidine scintigraphy scanning. She was successfully treated by surgical excision with the aid of cardiopulmonary bypass and perioperative alpha and beta adrenergic blockade.

Background Among selected patients undergoing major noncardiac surgery, β-adrenergic blockade has been shown to reduce the risk for postoperative cardiac complications and mortality. We sought to determine how often postoperative MI might be considered preventable through appropriate use of these medications. Methods We reviewed the medical records of patients who developed a postoperative MI between January 1, 1998, and October 31, 2001, at Baystate Medical Center, a 570-bed community-based teaching hospital in Springfield, Mass. We calculated a Revised Cardiac Risk Index score and used criteria from previous randomized trials to determine whether patients would have been candidates for perioperative β-adrenergic blockade. Postoperative MI was considered potentially preventable if the patient appeared to have been an ideal candidate for β-blocker therapy but did not receive it before the infarction. We compared the mortality of ideal candidates who did and did not receive β-blockers before their infarction using multivariable logistic regression. Results Seventy (97%) of the 72 patients who developed postoperative MI could have been identified as being at increased risk for cardiac complications, and 58 (81%) appeared to be ideal perioperative β-blocker candidates. Thirty ideal candidates (52%) were treated with β-blockers before the development of the infarction. Among ideal candidates, treatment with a β-blocker before infarction was associated with an odds ratio of in-hospital mortality of 0.19 (95% confidence interval, 0.04-0.87). Conclusions A large percentage of the postoperative MIs at our institution might have been prevented if a β-blocker had been administered to all ideal candidates around the time of surgery. Use of β-blockers before infarction may reduces overall mortality, even among patients who go on to develop this complication.

Beta-adrenergic blockers are often used in children to treat a variety of cardiovascular and noncardiovascular medical problems. The clinical experiences with beta-blockers in neonates, children, and adolescents are discussed in this comprehensive review.

Because of their hemodynamic and antiarrhythmic actions, beta-adrenergic blockers and calcium-entry blockers have been suggested for use in patients with myocardial infarction (MI) for reducing infarct size, preventing ventricular ectopy, and for prolonging life in survivors of acute MI. Experimental studies have suggested their usefulness in these areas. Clinical studies have demonstrated a role for beta-blockers in the hyperacute phase of MI, and in longterm treatment of infarct survivors. Calcium channel blockers appear to have somewhat less utility in patients with Q wave MIs, but may have an important role in therapy of the non-Q wave infarct.

Recent studies in man have shown a decrease in serum L-T3 (T3) levels in subjects treated with DL-propranolol, but the mechanism of this effect is unknown. Isolated rat renal tubules were used to study the effect of propranolol and related drugs on the formation of T3 from L-T4 (T4). Racemic (DL) propranolol at 100 microM inhibited the net formation of T3 from T4 by 35% (P less than 0.01). The D- and L-isomers of propranolol were also potent in inhibiting T3 formation, but the beta-blockers atenolol and sotalol, which have no significant membrane-stabilizing activity, had no effect at similar concentrations. Quinidine inhibited T3 formation, with a dose-response curve which was similar over the concentrations studied to that of DL-propranolol. L-Epinephrine and L-isoproterenol had no effect on T3 formation, and equimolar amounts of L-isoproterenol did not prevent the inhibition of T3 formation by DL-propranolol. cAMP production was stimulated by 200 micro M L-isoproterenol, and this was blocked by an equimolar concentration of DL-propranolol but not of D-propranolol. It is concluded that DL-propranolol directly inhibits net T3 formation from T4 in this system by a direct membrane-stabilizing or quinidine-like action and not by specific beta-blockade.

The effect of β-adrenergic blockade by intravenous dl-propranolol on pulse rate, tremor and Achilles reflex time has been compared with the effect of inactive d-propranolol and saline alone in anxious and thyrotoxic subjects. β-blockade significantly reduced pulse rate, decreased the amplitude of tremor, and prolonged reflex time in both groups.