Twitter for professional use in electrophysiology: practical guide for #EPeeps.

Abstract Social media (SoMe) becomes more and more popular in the cardiological community. Among them, Twitter is an emerging and dynamic medium to connect, communicate and educate academic and clinical cardiologists. However, in contrast to traditional scientific communications, the content provided through SoMe is not peer-reviewed and may not necessarily always represent scientific evidence or may even be used to unjustifiably promote therapies for commercial purposes. For the unintended, this means of communication might be appear difficult to handle. This article aims to provide a practical guide on how to use Twitter efficiently for professional use to keep yourself up-to-date about new techniques, the latest study results and news presented at national or international conferences. Additionally, important limitations will be discussed

Systemic, pulmonary and coronary haemodynamic actions of the novel dopamine receptor agonist in awake pigs at rest and during treadmill exercise Z1046

1. In view of the potential therapeutic application of specific dopamine receptor agonists in the treatment of hypertension and left ventricular dysfunction, we investigated the cardiovascular actions of the novel mixed D1/D2 dopamine receptor agonist Z1046 in awake pigs at rest and during treadmill exercise. 2. Thirteen swine were chronically instrumented under sterile conditions for measurement of systemic, pulmonary, and coronary haemodynamics. Regional blood flows were determined with the radioactive microsphere technique. 3. Z1046 (1, 10, 100 μg kg-1, i.v.) produced dose-dependent reductions in central aortic blood pressure (up to 27 ± 3%, P ≤ 0.05) in awake resting pigs which was accompanied by only minimal reflex activation of the sympathetic nervous system. The hypotensive response was principally the result of peripheral vasodilatation (system vascular resistance decreased up to 35 ± 4%, P ≤ 0.05), which was located in the cerebral, coronary, renal, mesenteric, adrenal, splenic and skeletal muscular vascular beds (vascular resistance decreased up to 30-40% after the highest dose in these beds). Only in the cerebral and mesenteric bed was the vasodilatation sufficiently large to overcome the decrease in blood pressure and result in an increased blood flow; the vasodilatation in the coronary bed was most likely due to autoregulation as neither coronary blood flow nor myocardial oxygen demand were changed significantly by Z1046. The systemic vasodilatation that was caused by the highest i.v. dose (100 μg kg-1) was accompanied by transient and minor increases in heart rate (15 ± 5%, P ≤ 0.05) and cardiac output (15 ± 5%, P ≤ 0.05) whereas after 10 μg kg-1, i.v., a slight decrease in cardiac output also contributed to the hypotension. Z1046 had no effect on pulmonary vascular resistance. 4. The systemic vasodilator responses to Z1046 (100 μg kg-1, i.v.) were sustained during treadmill exercise (2-4 km h-1 which produced heart rates of up to 233 ± 10 beats min-1), but with increasing treadmill speed attenuation of the exercise-induced increase in heart rate (-11 ± 3%, P ≤ 0.05) and hence cardiac output (-10 ± 3%, P ≤ 0.05) (as stroke volume was not altered by Z1046) contributed significantly to a lower aortic blood pressure (-20 ± 3%, P ≤ 0.05). Z1046 had no effect on pulmonary vascular resistance during exercise. 5. Oral administration of Z1046 (0.5, 1.5 mg kg-1) produced a fall in central aortic blood pressure (up to 15 ± 3%, P ≤ 0.05), which developed gradually during the first 90 min and lasted up to 4 h after administration, again with negligible changes in heart rate and LVdP/dt(max). 6. Neither non-selective α- and β-adrenoceptor blockade, nor selective α2-adrenoceptor blockade altered the vasodilator actions of Z1046, but non-selective α- and β-adrenoceptor blockade abolished the cardiac responses to dopamine receptor stimulation, suggesting that its cardiac actions were principally caused by D2-receptor-mediated inhibition of catecholamine release, whereas the vasodilator response was probably the result of vascular D1-receptor stimulation. 7. In conclusion, the novel dopamine receptor agonist Z1046 is an effective blood pressure lowering agent that elicits minimal reflex activation of the sympathetic nervous system in awake resting pigs. Systemic vasodilatation was not affected by combined α- and β-adrenoceptor blockade, which is consistent with a predominantly D1 receptor-dependent vasodilator mechanism. The hypotensive effect is maintained during treadmill exercise during which systemic vasodilatation and a lower cardiac output both contribute to the blood pressure lowering actions of Z1046. The cardiovascular profile of this orally active compound warrants further investigation of this class of drugs in experimental and clinical hypertension.</p

Systemic, pulmonary and coronary haemodynamic actions of the novel dopamine receptor agonist in awake pigs at rest and during treadmill exercise Z1046

1. In view of the potential therapeutic application of specific dopamine receptor agonists in the treatment of hypertension and left ventricular dysfunction, we investigated the cardiovascular actions of the novel mixed D1/D2 dopamine receptor agonist Z1046 in awake pigs at rest and during treadmill exercise. 2. Thirteen swine were chronically instrumented under sterile conditions for measurement of systemic, pulmonary, and coronary haemodynamics. Regional blood flows were determined with the radioactive microsphere technique. 3. Z1046 (1, 10, 100 μg kg-1, i.v.) produced dose-dependent reductions in central aortic blood pressure (up to 27 ± 3%, P ≤ 0.05) in awake resting pigs which was accompanied by only minimal reflex activation of the sympathetic nervous system. The hypotensive response was principally the result of peripheral vasodilatation (system vascular resistance decreased up to 35 ± 4%, P ≤ 0.05), which was located in the cerebral, coronary, renal, mesenteric, adrenal, splenic and skeletal muscular vascular beds (vascular resistance decreased up to 30-40% after the highest dose in these beds). Only in the cerebral and mesenteric bed was the vasodilatation sufficiently large to overcome the decrease in blood pressure and result in an increased blood flow; the vasodilatation in the coronary bed was most likely due to autoregulation as neither coronary blood flow nor myocardial oxygen demand were changed significantly by Z1046. The systemic vasodilatation that was caused by the highest i.v. dose (100 μg kg-1) was accompanied by transient and minor increases in heart rate (15 ± 5%, P ≤ 0.05) and cardiac output (15 ± 5%, P ≤ 0.05) whereas after 10 μg kg-1, i.v., a slight decrease in cardiac output also contributed to the hypotension. Z1046 had no effect on pulmonary vascular resistance. 4. The systemic vasodilator responses to Z1046 (100 μg kg-1, i.v.) were sustained during treadmill exercise (2-4 km h-1 which produced heart rates of up to 233 ± 10 beats min-1), but with increasing treadmill speed attenuation of the exercise-induced increase in heart rate (-11 ± 3%, P ≤ 0.05) and hence cardiac output (-10 ± 3%, P ≤ 0.05) (as stroke volume was not altered by Z1046) contributed significantly to a lower aortic blood pressure (-20 ± 3%, P ≤ 0.05). Z1046 had no effect on pulmonary vascular resistance during exercise. 5. Oral administration of Z1046 (0.5, 1.5 mg kg-1) produced a fall in central aortic blood pressure (up to 15 ± 3%, P ≤ 0.05), which developed gradually during the first 90 min and lasted up to 4 h after administration, again with negligible changes in heart rate and LVdP/dt(max). 6. Neither non-selective α- and β-adrenoceptor blockade, nor selective α2-adrenoceptor blockade altered the vasodilator actions of Z1046, but non-selective α- and β-adrenoceptor blockade abolished the cardiac responses to dopamine receptor stimulation, suggesting that its cardiac actions were principally caused by D2-receptor-mediated inhibition of catecholamine release, whereas the vasodilator response was probably the result of vascular D1-receptor stimulation. 7. In conclusion, the novel dopamine receptor agonist Z1046 is an effective blood pressure lowering agent that elicits minimal reflex activation of the sympathetic nervous system in awake resting pigs. Systemic vasodilatation was not affected by combined α- and β-adrenoceptor blockade, which is consistent with a predominantly D1 receptor-dependent vasodilator mechanism. The hypotensive effect is maintained during treadmill exercise during which systemic vasodilatation and a lower cardiac output both contribute to the blood pressure lowering actions of Z1046. The cardiovascular profile of this orally active compound warrants further investigation of this class of drugs in experimental and clinical hypertension.</p

Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade prevent cardiac remodeling in pigs after myocardial infarction: role of tissue angiotensin II

BACKGROUND: The mechanisms behind the beneficial effects of renin-angiotensin system blockade after myocardial infarction (MI) are not fully elucidated but may include interference with tissue angiotensin II (Ang II). METHODS AND RESULTS: Forty-nine pigs underwent coronary artery ligation or sham operation and were studied up to 6 weeks. To determine coronary angiotensin I (Ang I) to Ang II conversion and to distinguish plasma-derived Ang II from locally synthesized Ang II, (125)I-labeled and endogenous Ang I and II were measured in plasma and in infarcted and noninfarcted left ventricle (LV) during (125)I-Ang I infusion. Ang II type 1 (AT(1)) receptor-mediated uptake of circulating (125)I-Ang II was increased at 1 and 3 weeks in noninfarcted LV, and this uptake was the main cause of the transient elevation in Ang II levels in the noninfarcted LV at 1 week. Ang II levels and AT(1) receptor-mediated uptake of circulating Ang II were reduced in the infarct area at all time points. Coronary Ang I to Ang II conversion was unaffected by MI. Captopril and the AT(1) receptor antagonist eprosartan attenuated postinfarct remodeling, although both drugs increased cardiac Ang II production. Captopril blocked coronary conversion by >80% and normalized Ang II uptake in the noninfarcted LV. Eprosartan did not affect coronary conversion and blocked cardiac Ang II uptake by >90%. CONCLUSIONS: Both circulating and locally generated Ang II contribute to remodeling after MI. The rise in tissue Ang II production during angiotensin-converting enzyme inhibition and AT(1) receptor blockade suggests that the antihypertrophic effects of these drugs result not only from diminished AT(1) receptor stimulation but also from increased stimulation of growth-inhibitory Ang II type 2 receptors

A human embryonic kidney 293T cell line mutated at the Golgi -mannosidase II locus

Disruption of Golgi -mannosidase II activity can result in type II congenital dyserythropoietic anemia and can induce lupus-like autoimmunity in mice. Here, we isolate a mutant human embryonic kidney (HEK) 293T cell line, called Lec36, that displays sensitivity to ricin that lies between the parental HEK 293T cells, whose secreted and membrane-expressed proteins are dominated by complex-type glycosylation, and 293S Lec1 cells, which only produce oligomannose-type N-linked glycans. The stem cell marker, 19A, was transiently expressed in the HEK 293T Lec36 cells, and in parental HEK 293T cells with and without the potent Golgi -mannosidase II inhibitor, swainsonine. Negative-ion nano-electrospray ionization mass spectra of the 19A N-linked glycans from HEK 293T Lec36 and swainsonine-treated HEK 293T cells were qualitatively indistinguishable and, as shown by collision-induced dissociation spectra, dominated by hybrid-type glycosylation. Nucleotide sequencing revealed mutations in each allele of MAN2A1, the gene encoding Golgi -mannosidase II: a point mutation in one allele mapping to the active site and an in-frame deletion of twelve-nucleotides in the other. Expression of wild-type but not the mutant MAN2A1 alleles in Lec36 cells restored processing of the 19A reporter glycoprotein to complex-type glycosylation. The Lec36 cell line will be useful for expressing therapeutic glycoproteins with hybrid-type glycans and provides a sensitive host for detecting mutations in human MAN2A1 causing type II congenital dyserythropoietic anemia

Improving mental well-being in psychocardiology—a feasibility trial for a non-blended web application as a brief metacognitive-based intervention in cardiovascular disease patients

Background: Many patients with cardiovascular disease also show a high comorbidity of mental disorders, especially such as anxiety and depression. This is, in turn, associated with a decrease in the quality of life. Psychocardiological treatment options are currently limited. Hence, there is a need for novel and accessible psychological help. Recently, we demonstrated that a brief face-to-face metacognitive therapy (MCT) based intervention is promising in treating anxiety and depression. Here, we aim to translate the face-to-face approach into digital application and explore the feasibility of this approach. Methods: We translated a validated brief psychocardiological intervention into a novel non-blended web app. The data of 18 patients suffering from various cardiac conditions but without diagnosed mental illness were analyzed after using the web app over a two-week period in a feasibility trial. The aim was whether a non-blended web app based MCT approach is feasible in the group of cardiovascular patients with cardiovascular disease. Results: Overall, patients were able to use the web app and rated it as satisfactory and beneficial. In addition, there was first indication that using the app improved the cardiac patients’ subjectively perceived health and reduced their anxiety. Therefore, the approach seems feasible for a future randomized controlled trial. Conclusion: Applying a metacognitive-based brief intervention via a non-blended web app seems to show good acceptance and feasibility in a small target group of patients with CVD. Future studies should further develop, improve and validate digital psychotherapy approaches, especially in patient groups with a lack of access to standard psychotherapeutic care

Risk for life-threatening arrhythmia in newly diagnosed peripartum cardiomyopathy with low ejection fraction: a German multi-centre analysis

Introduction Peripartum cardiomyopathy (PPCM) is a rare cardiomyopathy characterized by an acute reduction in left ventricular ejection fraction (LVEF). Sudden deaths during the course of PPCM are reported to be elevated, the underlying mechanisms remains unknown. The aim of the present multi-centre study was to evaluate the arrhythmia burden in a multi-centre approach in patients with PPCM using a wearable cardioverter/defibrillator (WCD). Methods and results Forty-nine patients from 16 German centres with newly diagnosed PPCM and LVEF <= 35% receiving a WCD were included in this retrospective analysis. Mean follow-up was 15 +/- 10 months. At diagnosis, mean age was 33 +/- 5 years, parity was 2.1 +/- 1.6, LVEF was 21 +/- 7%, NYHA functional class was 3.4 +/- 0.7. Mean wear time was 120 +/- 106 days, mean wear time per day was 21.4 +/- 3.3 h. Six (12%) patients presented eight ventricular tachyarrhythmias during WCD period: five episodes of VF, two sustained ventricular tachycardia (VT) and one non-sustained VT occurred. Conclusion This multicentre study underpins the elevated risk for ventricular tachyarrhythmias in patients with newly diagnosed PPCM and reduced LVEF. A WCD should be considered for 3-6 months in these patients to prevent sudden cardiac death from ventricular tachyarrhythmias