In cardiac myocytes, the sarcomeric Z-disc protein telethonin is constitutively bis-phosphorylated at C-terminal residues S157 and S161; however, the functional significance of this phosphorylation is not known. We sought to assess the significance of telethonin phosphorylation , using a novel knock-in (KI) mouse model generated to express non-phosphorylatable telethonin ( ). and wild-type (WT) littermates were characterized by echocardiography at baseline and after sustained β-adrenergic stimulation isoprenaline infusion.
View Article and Find Full Text PDFBackground And Purpose: Antiarrhythmic β-blockers are used in patients at risk of myocardial ischaemia, but the survival benefit and mechanisms are unclear. We hypothesized that β-blockers do not prevent ventricular fibrillation (VF) but instead inhibit the ability of catecholamines to facilitate ischaemia-induced VF, limiting the scope of their usefulness.
Experimental Approach: ECGs were analysed from ischaemic Langendorff-perfused rat hearts perfused with adrenoceptor antagonists and/or exogenous catecholamines (CATs: 313Â nM noradrenaline + 75Â nM adrenaline) in a blinded and randomized study.
What is the central question of this study? Rate-pressure product (RPP) is commonly used as an index of cardiac 'effort'. In canine and human hearts (which have a positive force-frequency relationship), RPP is linearly correlated with oxygen consumption and has therefore been widely adopted as a species-independent index of cardiac work. However, given that isolated rodent hearts demonstrate a negative force-frequency relationship, its use in this model requires validation.
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