Mehrflammiger Brenner mit gleichzeitiger Luft- und Gasregulirung

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What parameters affect left ventricular diastolic flow propagation velocity? in vitro studies using color m-mode doppler echocardiography

BACKGROUND: Insufficient data describe the relationship of hemodynamic parameters to left ventricular (LV) diastolic flow propagation velocity (Vp) measured using color M-mode Doppler echocardiography. METHODS: An in vitro LV model used to simulate LV diastolic inflow with Vp measured under conditions of varying: 1) Stroke volume, 2) heart rate (HR), 3) LV volume, 4) LV compliance, and 5) transmitral flow (TMF) waveforms (Type 1: constant low diastasis flow and Type 2: no diastasis flow). RESULTS: Univariate analysis revealed excellent correlations of Vp with stroke volume (r = 0.98), LV compliance (r = 0.94), and HR with Type 1 TMF (r = 0.97). However, with Type 2 TMF, HR was not associated with Vp. LV volume was not related to Vp under low compliance, but inversely related to Vp under high compliance conditions (r = -0.56). CONCLUSION: These in vitro findings may help elucidate the relationship of hemodynamic parameters to early diastolic LV filling

Gut enterochromaffin cells drive visceral pain and anxiety

Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain1 . For the growing population aficted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved2 . Irritable bowel syndrome also exhibits a strong sex bias, aficting women three times more than men1 . Here, we focus on enterochromafn (EC) cells, which are rare excitable, serotonergic neuroendocrine cells in the gut epithelium3–5 . EC cells detect and transduce noxious stimuli to nearby mucosal nerve endings3,6 but involvement of this signalling pathway in visceral pain and attendant sex diferences has not been assessed. By enhancing or suppressing EC cell function in vivo, we show that these cells are sufcient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterial short-chain fatty acid associated with GI infammation7,8 . Remarkably, prolonged EC cell activation produced persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Furthermore, perturbing EC cell activity promoted anxiety-like behaviours which normalized after blockade of serotonergic signalling. Sex diferences were noted across a range of paradigms, indicating that the EC cell–mucosal afferent circuit is tonically engaged in females. Our findings validate a critical role for EC cell–mucosal afferent signalling in acute and persistent GI pain, in addition to highlighting genetic models for studying visceral hypersensitivity and the sex bias of gut pain.James R. Bayrer, Joel Castro, Archana Venkataraman, Kouki K. Touhara, Nathan D. Rossen, Ryan D. Morrie, Jessica Maddern, Aenea Hendry, Kristina N. Braverman, Sonia Garcia-Caraballo, Gudrun Schober, Mariana Brizuela, Fernanda M. Castro Navarro, Carla Bueno-Silva, Holly A. Ingraham, Stuart M. Brierley, David Juliu

Gut enterochromaffin cells drive visceral pain and anxiety

Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain1. For the growing population afflicted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved2. Irritable bowel syndrome also exhibits a strong sex bias, afflicting women three times more than men1. Here, we focus on enterochromaffin (EC) cells, which are rare excitable, serotonergic neuroendocrine cells in the gut epithelium3-5. EC cells detect and transduce noxious stimuli to nearby mucosal nerve endings3,6 but involvement of this signalling pathway in visceral pain and attendant sex differences has not been assessed. By enhancing or suppressing EC cell function in vivo, we show that these cells are sufficient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterial short-chain fatty acid associated with GI inflammation7,8. Remarkably, prolonged EC cell activation produced persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Furthermore, perturbing EC cell activity promoted anxiety-like behaviours which normalized after blockade of serotonergic signalling. Sex differences were noted across a range of paradigms, indicating that the EC cell-mucosal afferent circuit is tonically engaged in females. Our findings validate a critical role for EC cell-mucosal afferent signalling in acute and persistent GI pain, in addition to highlighting genetic models for studying visceral hypersensitivity and the sex bias of gut pain