Background-Takotsubo cardiomyopathy is an acute heart failure syndrome characterized by myocardial hypocontractility from the mid left ventricle to the apex. It is precipitated by extreme stress and can be triggered by intravenous catecholamine administration, particularly epinephrine. Despite its grave presentation, Takotsubo cardiomyopathy is rapidly reversible, with generally good prognosis. We hypothesized that this represents switching of epinephrine signaling through the pleiotropic ␤ 2 -adrenergic receptor (␤ 2 AR) from canonical stimulatory G-protein-activated cardiostimulant to inhibitory G-protein-activated cardiodepressant pathways. Methods and Results-We describe an in vivo rat model in which a high intravenous epinephrine, but not norepinephrine, bolus produces the characteristic reversible apical depression of myocardial contraction coupled with basal hypercontractility. The effect is prevented via G i inactivation by pertussis toxin pretreatment. ␤ 2 AR number and functional responses were greater in isolated apical cardiomyocytes than in basal cardiomyocytes, which confirmed the higher apical sensitivity and response to circulating epinephrine. In vitro studies demonstrated high-dose epinephrine can induce direct cardiomyocyte cardiodepression and cardioprotection in a ␤ 2 AR-Gi-dependent manner. Preventing epinephrine-G i effects increased mortality in the Takotsubo model, whereas ␤-blockers that activate ␤ 2 AR-G i exacerbated the epinephrine-dependent negative inotropic effects without further deaths. In contrast, levosimendan rescued the acute cardiac dysfunction without increased mortality. Conclusions-We suggest that biased agonism of epinephrine for ␤ 2 AR-G s at low concentrations and for G i at high concentrations underpins the acute apical cardiodepression observed in Takotsubo cardiomyopathy, with an apical-basal gradient in ␤ 2 ARs explaining the differential regional responses. We suggest this epinephrine-specific ␤ 2 AR-G i signaling may have evolved as a cardioprotective strategy to limit catecholamine-induced myocardial toxicity during acute stress. (Circulation. 2012;126:697-706.)Key Words: acute heart failure Ⅲ catecholamines Ⅲ receptors, adrenergic, beta Ⅲ Takotsubo syndrome T here has been a rapid increase in the recognition of a syndrome of acute and severe but reversible heart failure called Takotsubo or stress cardiomyopathy, 1-3 also known as broken heart syndrome, which usually follows within hours of an identifiable emotional, psychological, or physical stress. Takotsubo cardiomyopathy mimics symptoms of acute myocardial infarction but is distinguished by the lack of coronary occlusion and by characteristic regional wall-motion abnormalities, classically a virtual apical ballooning appearance caused by a hypercontractile base of the heart relative to hypokinetic or akinetic apical and mid left ventricular myocardium, the latter extending beyond a single coronary artery territory. Clinical Perspective on p 706The pathophysiological mechanisms for this increasingly recogn...

These authors contributed equally to this work. ⇤ Corresponding authors.The sudden outbreak of novel coronavirus 2019 (COVID-19) increased the diagnostic burden of radiologists. In the time of an epidemic crisis, we hoped artificial intelligence (AI) to help reduce physician workload in regions with the outbreak, and improve the diagnosis accuracy for physicians before they could acquire enough experience with the new disease. Here, we present our experience in building and deploying an AI system that automatically analyzes CT images to detect COVID-19 pneumonia features. Different from conventional medical AI, we were dealing with an epidemic crisis. Working in an interdisciplinary team of over 30 people with medical and / or AI background, geographically distributed in Beijing and Wuhan, we were able to overcome a series of challenges in this particular situation and deploy the system in four weeks. Using 1,136 training cases (723 positives for COVID-19) from five hospitals, we were able to achieve a sensitivity of 0.974 and specificity of 0.922 on the test dataset, which included a variety of pulmonary diseases. Besides, the system automatically highlighted all lesion regions for faster examination. As of today, we have deployed the system 2 All rights reserved. No reuse allowed without permission.

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Two-dimensional (2-D) speckle tracking echocardiography (STE) accurately quantifies circumferential strain (S(circ)) and radial strain (S(rad)) in humans and in large and small animals. This study was performed to assess sensitivity of S(circ) and S(rad) to left ventricular (LV) dysfunction in mouse models. We performed 2-D and M-mode echocardiography 1) in 6 mice during superficial and profound isoflurane anesthesia, 2) serially in 12 mice to monitor the development of heart failure induced by transverse aortic constriction (TAC) and in 8 corresponding control mice, and 3) in 26 mice with varying degrees of TAC-induced heart failure and 12 corresponding control mice immediately before euthanasia. Fractional shortening (FS) and LV mass were measured from standard M-mode tracings, whereas S(circ) and S(rad) were derived by STE. Percent fibrosis and myocyte diameters were assessed from whole heart cross-sectional specimens stained by Masson trichrome. Profound isoflurane anesthesia decreased S(circ) (P = 0.027) but not S(rad) (P > 0.05). Mice subjected to TAC showed an immediate and sustained decrease in FS (P = 0.035), S(circ) (P = 0.016), and S(rad) (P = 0.012). S(circ) showed better correlation with FS (r = 0.56 and P < 0.0001) and LV mass (r = 0.42 and P = 0.0003) than S(rad) (r = 0.54 and P < 0.0001 for FS and r = 0.37 and P = 0.014 for LV mass, respectively). Percent fibrosis correlated better with S(circ) (r = 0.46 and P = 0.004) than with S(rad) (r = -0.32 and P = 0.05), whereas myocyte diameter showed similar correlation with both strains (r = 0.45 and r = -0.44, respectively, and P = 0.006 for both). STE correctly identifies LV dysfunction and histological changes in mice and can be used for the serial assessment of cardiac remodeling in murine models.

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We conclude that SLN may play an important role in regulating the SR calcium ATPase pump, possibly by interacting with phospholamban.

BackgroundAs a systemic disease, atherosclerosis commonly affects intracranial and extracranial carotid arteries simultaneously which is defined as co-existing plaques. Previous studies demonstrated that co-existing atherosclerotic diseases are significantly associated with ischemic cerebrovascular events. The aim of this study was to investigate the characteristics of co-existing intracranial and extracranial carotid atherosclerotic plaques and their relationships with recurrent stroke by using 3D multi-contrast magnetic resonance (MR) vessel wall imaging.MethodsPatients with recent cerebrovascular symptoms in anterior circulation and at least one carotid plaque were recruited. All patients underwent cardiovascular magnetic resonance (CMR) for brain and intracranial and extracranial arteries. Presence/absence of atherosclerotic plaque at each arterial segment was identified. The maximum wall thickness (Max WT), length, stenosis of each plaque was measured. The presence/absence of calcification, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH) was assessed. Cerebral old and acute infarcts in anterior circulation were evaluated.ResultsFifty-eight patients (mean age: 58.0 ± 8.5 years old, 34 males) were recruited. Of the 58 patients, co-existing intracranial and extracranial carotid artery plaques were found in 45 patients (77.6%), of which 7 (15.6%) had first time acute stroke and 26 (57.8%) had recurrent stroke. For these 33 patients with stroke, the number of intracranial plaques (OR = 11.26; 95% CI, 1.27–100; p = 0.030) and co-existing intracranial and extracranial carotid artery plaques (OR = 2.42; 95% CI, 1.04–5.64; p = 0.040) was significantly associated with recurrent stroke. After adjusting for traditional risk factors, the number of co-existing plaques was still significantly correlated with recurrent stroke (OR = 3.31; 95% CI, 1.09–10.08; p = 0.035). No correlations were found between recurrent stroke and Max WT, length, stenosis, and compositions of plaques.ConclusionsCo-existing intracranial and extracranial carotid artery plaques are prevalent in symptomatic patients and the number of co-existing plaques is independently associated with the risk of recurrent stroke.

Second-look arthroscopy was the most dependable way to determine meniscal healing. Clinical assessment had obvious limitations in diagnosing healed menisci. On MRI examination, T2-weighted sequences had obviously higher specificity and accuracy, while PD and T1 had higher sensitivity. The diagnostic value could be improved by a combined application of different sequences.