Prognostic value of pharmacotherapy in patients with atrial fibrillation after radiofrequency ablation

The aim of the work: to evaluate the prognostic effect of pharmacotherapy before and after radiofrequency ablation (RFA) in patients with atrial fibrillation (AF) on all-cause mortality, supraventricular arrhythmia recurrence and non-fatal cardiovascular events. Materials and methods. Patients with paroxysmal, persistent and long-term persistent forms of AF were examined before and after RFA – isolation of pulmonary veins. The primary endpoint was patient survival, secondary – a composite endpoint of freedom from recurrence and/or non-fatal cardiovascular events for 2 years of a follow-up. Frequency and doses of pharmacotherapy were evaluated. Standard statistical procedures were used for initial data evaluation. Results. 116 patients were consecutively enrolled in the study. In the long-term post-ablation, 23 patients (19.8 %) continued to take amiodarone, 2 patients (1.7 %) – propafenone for arrhythmic events, 38 patients (32.8 %) needed anticoagulants, and 37 patients (31.9 %) received beta-adrenoceptor blockers over the entire follow-up period. The use of RAAS inhibitors decreased from 81.0 % before the ablation to 56.0 % in the long-term period following RFA. Multifactorial logistic regression analysis showed that the prolonged (more than 3 months) anticoagulation (P = 0.032) after RFA was an independent predictor of patient survival in the two-year follow-up; doses of anticoagulants before the procedure, use and doses of beta-adrenoceptor blockers in the long-term post-ablation period were associated with the secondary endpoint. Conclusions. RFA for AF significantly reduced the frequency of medications use in the long-term postoperatively. Independent predictors of survival were the doses of anticoagulants more than 3 months after ablation, arrhythmia recurrence and non-fatal cardiovascular events – the doses of anticoagulants before the procedure, and the use and doses of beta-adrenoceptor blockers in the long-term period after RFA.

Adrenergic Receptor Beta 2and 3 Polymorphism Modulate Gastro Intestinal Motility in Ttype 2 Diabetes Mellitus Patients

BackgroundIndividuals with type 2diabetes mellitus (T2DM) commonly present with gastro intestinal symptoms. Exact pathophysiology behind these symptoms is not elucidated. Previous studies reported the role of adrenoceptors on gut motility. However, no study has been conducted to observe whether adrenergic beta receptor (ADRB) 2 and 3 gene polymorphism could influence the gut motility in T2DM. Materials and Methods:Three hundred T2DM patients and 200 age and sex matched healthy controls were enrolled for this study. Participants were subjected to lactulose hydrogen breath test for estimation of orocecal transit time (OCTT). To carry out polymorphism study, buffy coat of EDTA blood was used for DNA isolation followed by polymerase chain reaction and restriction fragment length polymorphism. Results:In this study, the frequency of C allele as well as CC genotype of ADRB3 gene polymorphism and A allele as well as AA genotype of ADRB2 gene polymorphism were significantly higher in patients than controls and was associated with increased risk for T2DM. On comparison of gut motility, OCTT was found to be significantly prolonged (p<0.01) in individuals with CC genotype compared to TT or CT genotype in ADRB3 polymorphism and AA genotype, compared to AG and GG genotype in case of ADRB2 polymorphism. Combined effect of both adrenoceptors on gut motility revealed that individuals having AG or AA genotype in combination with other genotypes had significantly prolonged OCTT. Conclusion:It could be concluded that beta adrenoceptor gene polymorphism has significant role on regulation of gut motility in T2DM.

Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies

Objective: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. Design: This was a controlled and prospective ex vivo study. Setting: The work was conducted as a collaboration between 4 academic departments. Materials and Methods: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. Results: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). Limitations: These results require now to be placed into a firm clinical context. Conclusions: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.

Focal Seizure in A Patient Receiving Terbutaline : A Case Report

Terbutaline sulfate is a β2 adrenergic agonist agent used in treatment of asthma. Terbutaline’s adverse effects such as skeletal muscle tremor, tachycardia, hyperglicemia and various metabolic effects are mediated by beta-adrenoceptor stimulation .Terbutaline is not recommend use for children younger than 2 years of age.The case of a 44-day-old girl who experienced focal seizure following oral terbutaline sulfate use is presented.For exclusion of other causes of focal seizure, we used brain magnetic resonance imaging, and electroencephalography and it is concluded that focal seizure developed as a result of terbutaline sulfate use

High‐Dose Glucagon Has Hemodynamic Effects Regardless of Cardiac Beta‐Adrenoceptor Blockade: A Randomized Clinical Trial

Background Intravenous high‐dose glucagon is a recommended antidote against beta‐blocker poisonings, but clinical effects are unclear. We therefore investigated hemodynamic effects and safety of high‐dose glucagon with and without concomitant beta‐blockade. Methods and Results In a randomized crossover study, 10 healthy men received combinations of esmolol (1.25 mg/kg bolus+0.75 mg/kg/min infusion), glucagon (50 µg/kg), and identical volumes of saline placebo on 5 separate days in random order (saline+saline; esmolol+saline; esmolol+glucagon bolus; saline+glucagon infusion; saline+glucagon bolus). On individual days, esmolol/saline was infused from −15 to 30 minutes. Glucagon/saline was administered from 0 minutes as a 2‐minute intravenous bolus or as a 30‐minute infusion (same total glucagon dose). End points were hemodynamic and adverse effects of glucagon compared with saline. Compared with saline, glucagon bolus increased mean heart rate by 13.0 beats per minute (95% CI, 8.0–18.0; P <0.001), systolic blood pressure by 15.6 mm Hg (95% CI, 8.0–23.2; P =0.002), diastolic blood pressure by 9.4 mm Hg (95% CI, 6.3–12.6; P <0.001), and cardiac output by 18.0 % (95% CI, 9.7–26.9; P =0.003) at the 5‐minute time point on days without beta‐blockade. Similar effects of glucagon bolus occurred on days with beta‐blockade and between 15 and 30 minutes during infusion. Hemodynamic effects of glucagon thus reflected pharmacologic glucagon plasma concentrations. Glucagon‐induced nausea occurred in 80% of participants despite ondansetron pretreatment. Conclusions High‐dose glucagon boluses had significant hemodynamic effects regardless of beta‐blockade. A glucagon infusion had comparable and apparently longer‐lasting effects compared with bolus, indicating that infusion may be preferable to bolus injections. Registration Information URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03533179.

Abstract 475: Beta-adrenoceptor Stimulation Uniquely Regulates Exosome Micro-rna Content Secreted From Cardiomyocytes in vitro and Those Found in vivo Circulating in Blood

Background and Purpose: The influence of β-adrenoceptor (βAR) signaling on the regulation of exosomes secreted from cardiomyocytes is unknown and since catecholamines are increased in heart failure (HF), there is interest in uncovering whether βARs can induce specific changes in the content of circulating blood exosomes in HF. In this study, we have evaluated whether βAR stimulation by isoproterenol (ISO) on neonatal rat ventricle myocytes (NRVMs) and in vivo in mice can alter the number, size and microRNA (miR) content of secreted exosomes. Methods and Results: ISO treatment of NRVMs did not change exosome number and size of compared than vehicle (PBS). After purifying total RNA from treated myocytes and secreted exosomes, we evaluated the expression level of 37 candidate miR’s, which were selected from previous microarray data. We found that ISO treatment decreased 14 miR’s (miR-222, -106a, -292a, -181b, -210, -489, -214, -1947, -195, -17, -7b, -93, -532 and -19a) in exosomes and in the myocytes themselves, mir-292a and -1947 were up regulated and mir-7b, down regulated. Further, ISO was then used to treat C57 mice via osmotic pump chronically. The number and size of exosomes purified from circulating blood was not changed after 2 and 8 weeks. We evaluated expression of the 14 miRs down-regulated in myocytes as well miR-1 and -21 (important cardiac miRs) both in the blood and hearts of ISO-treated mice. MiR-1 did not change in both blood exosomes and heart tissue and miR-21 was up-regulated in heart tissue but not in blood both at 2 and 8 weeks after ISO treatment. In addition, miRNA-489 and -7b was down-regulated in hearts with miR-214 and -292a up regulated. In blood exosomes, we found only down-regulation of miR-489 and -7b but not miR-214 and 292a. Conclusions: We found that the βAR agonist ISO altered exosomal miR contents but not exosome size and number from myocytes. Importantly, this was found in myocytes in culture and in vivo blood and myocardium that were treated with ISO but several differences were found and changes in blood and myocytes were not homogeneous. However, two miRs, mir-7b and -miR-489, both changes similarly from their origin (NRVMs or mouse hearts) and also in circulating blood exosomes. Therefore, these miRs may represent biomarkers for sympathetic nervous system abnormalities in HF and their therapeutic potential should be evaluated.