Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II

1 The calcineurin (CaN) enzyme-transcriptional pathway is critically involved in hypertrophy of heart muscle in some animal models. Currently there is no information concerning the regulation of CaN activation by endogenous agonists in human heart. 2 Human right ventricular trabeculae from explanted human ( 14 male/2 female) failing hearts were set up in a tissue bath and electrically paced at 1Hz and incubated with or without 100 nM endothelin-1 (ET-1), 10 mu M, angiotensin-II (Ang II) or 20 nM human urotensin-II (hUII) for 30 min. Tissues from four patients were incubated with 200 nM tacrolimus (FK506) for 30 min and then incubated in the presence or absence of ET-1 for a further 30 min. 3 ET-1 increased contractile force in all 13 patients (P < 0.001). Ang II and hUII increased contractile force in three out of eight and four out of 10 patients but overall nonsignificantly (P > 0.1). FK506 had no effect on contractile force (P = 0.12). 4 ET-1, Ang II and hUII increased calcineurin activity by 32, 71 and 15%, respectively, while FK506 reduced activity by 34%. ET-1 in the presence of FK506 did not restore calcineurin activity (P = 0.1). 5 There was no relationship between basal CaN activity and expression levels in the right ventricle. Increased levels of free phosphate were detected in ventricular homogenates that were incubated with PKC epsilon compared to samples incubated without PKCe. 6 Endogenous cardiostimulants which activate G alpha q-coupled receptors increase the activity of calcineurin in human heart following acute (30 min) exposure. PKC may contribute to this effect by increasing levels of phosphorylated calcineurin substrate.

Differential activation of the thoracic multifidus and longissimus thoracis during trunk rotation

Study Design. Cross-sectional study. Objective. To develop a technique to measure electromyographic (EMG) activity of deep and superficial paraspinal muscles at different thoracic levels and to investigate activity of these muscles during seated trunk rotation. Summary of Background Data. Few studies have compared activity of deep and superficial paraspinal muscles of the thorax during trunk rotation, and conflicting results have been presented. Conflicting data may result from recording techniques or variation in activity between thoracic regions. Methods. EMG recordings were made from deep (multifidus/ rotatores) and superficial ( longissimus) paraspinal muscles at T5, T8, and T11 using selective intramuscular electrodes. Ten subjects rotated the trunk to end of range in each direction. EMG amplitude was measured in neutral, at end of range, and during four epochs, which represented four quarters of the movement. Results. During trunk rotation in sitting, longissimus EMG either increased with ipsilateral rotation ( T5) or decreased with contralateral rotation ( T5, T8, T11). In contrast, multifidus EMG was more variable and was either active with rotation in both directions ( particularly T5) or with one movement direction. Conclusions. The deep and superficial muscles of the thorax are differentially active, and the patterns of activity differ between the regions of the thorax. Data from this study support the hypothesis that multifidus may have a role in control of segmental motion at T5. Variability in multifidus activity at T8 and T11 suggests that this muscle may also control coupling between rotation and lateral flexion.