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...

Background The COVID-19 pandemic posed a huge challenge to the education systems worldwide, forcing many countries to provisionally close educational institutions and deliver courses fully online. The aim of this study was to explore the quality of the online education in China for international medical and nursing students from low- and middle-income countries (LMICs) as well as the factors that influenced their satisfaction with online education during the COVID-19 pandemic. Methods Questionnaires were developed and administered to 316 international medical and nursing students and 120 teachers at a university in China. The Chi-square test was used to detect the influence of participants’ personal characteristics on their satisfaction with online education. The Kruskal–Wallis rank-sum test was employed to identify the negative and positive factors influencing the online education satisfaction. A binary logistic regression model was performed for multiple-factor analysis to determine the association of the different categories of influential factors—crisis-, learner-, instructor-, and course-related categories, with the online education satisfaction. Results Overall, 230 students (response rate 72.8%) and 95 teachers (response rate 79.2%) completed the survey. It was found that 36.5% of students and 61.1% of teachers were satisfied with the online education. Teachers’ professional title, students’ year of study, continent of origin and location of current residence significantly influenced the online education satisfaction. The most influential barrier for students was the severity of the COVID-19 situation and for teachers it was the sense of distance. The most influential facilitating factor for students was a well-accomplished course assignment and for teachers it was the successful administration of the online courses. Conclusions Several key factors have been identified that affected the attitudes of international health science students from LMICs and their teachers towards online education in China during the COVID-19 pandemic. To improve the online education outcome, medical schools are advised to promote the facilitating factors and cope with the barriers, by providing support for students and teaching faculties to deal with the anxiety caused by the pandemic, caring for the state of mind of in-China students away from home, maintaining the engagement of out-China students studying from afar and enhancing collaborations with overseas institutions to create practice opportunities at students’ local places.

Aging impairs eNOS-dependent reactivity of cerebral arterioles via an increase in superoxide produced by activation of NAD(P)H oxidase.