This study investigated the contribution of estrogen receptors (ERs) alpha and beta for epicardial coronary artery function, vascular NO bioactivity, and superoxide (O(2)(-)) formation. Porcine coronary rings were suspended in organ chambers and precontracted with prostaglandin F(2alpha) to determine direct effects of the selective ER agonists 4,4',4''-(4-propyl-[(1)H]pyrazole-1,3,5-triyl)tris-phenol (PPT) or 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) or the nonselective ER agonist 17beta-estradiol. Indirect effects on contractility to U46619 and relaxation to bradykinin were assessed and effects on NO, nitrite, and O(2)(-) formation were measured in cultured cells. Within 5 minutes, selective ERalpha activation by PPT, but not 17beta-estradiol or the ERbeta agonist DPN, caused rapid, NO-dependent, and endothelium-dependent relaxation (49+/-5%; P<0.001 versus ethanol). PPT also caused sustained endothelium- and NO-independent vasodilation similar to 17beta-estradiol after 60 minutes (72+/-3%; P<0.001 versus ethanol). DPN induced endothelium-dependent NO-independent relaxation via endothelium-dependent hyperpolarization (40+/-4%; P<0.01 versus ethanol). 17beta-Estradiol and PPT, but not DPN, attenuated the responses to U46619 and bradykinin. All of the ER agonists increased NO and nitrite formation in vascular endothelial but not smooth muscle cells and attenuated vascular smooth muscle cell O(2)(-) formation (P<0.001). ERalpha activation had the most potent effects on both nitrite formation and inhibiting O(2)(-) (P<0.05). These data demonstrate novel and differential mechanisms by which ERalpha and ERbeta activation control coronary artery vasoreactivity in males and females and regulate vascular NO and O(2)(-) formation. The findings indicate that coronary vascular effects of sex hormones differ with regard to affinity to ERalpha and ERbeta, which will contribute to beneficial and adverse effects of hormone replacement therapy.

BACKGROUND Long-term trends of the incidence and outcome of cardiogenic shock (CS) patients are scarce. We analyze for the first time trends in the incidence and outcome of CS during a 20-year period in Switzerland. METHODS AND RESULTS The AMIS (Acute Myocardial Infarction in Switzerland) Plus Registry enrolls patients with acute myocardial infarction from 83 hospitals in Switzerland. We analyzed trends in the incidence, treatment, and in-hospital mortality of patients with CS enrolled between 1997 and 2017. The impact of revascularization strategy on outcome was assessed for the time period 2005 to 2017. Among 52 808 patients enrolled, 963 patients were excluded because of missing data and 51 842 (98%) patients remained for the purpose of the present analysis. Overall, 4090 patients (7.9%) with a mean age of 69.6±12.5 years experienced acute myocardial infarction complicated by CS. Overall, rates of CS declined from 8.

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Rigorous blood glucose management is vital for individuals with diabetes to prevent states of too low blood glucose (hypoglycemia). While there are continuous glucose monitors available, they are expensive and not available for many patients. Related work suggests a correlation between the blood glucose level and physiological measures, such as heart rate variability. We therefore propose a machine learning model to detect hypoglycemia on basis of data from smartwatch sensors gathered in a proof-of-concept study. In further work, we want to integrate our model in wearables and warn individuals with diabetes of possible hypoglycemia. However, presenting just the detection output alone might be confusing to a patient especially if it is a false positive result. We thus use SHAP (SHapley Additive exPlanations) values for feature attribution and a method for subsequently explaining the model decision in a comprehensible way on smartwatches.