Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Assessment of RV stiffness and relaxation

Right ventricle (RV) has frequently been described as the forgotten ventricle in the circulation. However, its importance in various cardiac diseases is now unquestioned. This recognition has led to improved risk stratification and development of algorithms for intervention, which incorporate measurements of RV function as key components of the assessment of many conditions. The diastolic function plays an important role in determining ventricular filling and stroke volume. Abnormal left ventricular (LV) diastolic function has been recognized in many cardiovascular diseases and is associated with worse outcomes, including total mortality and hospitalizations due to heart failure. In this review, we define what global RV diastolic function is, and how to measure it. This article indicates the validation of kinematic model parameters for assessing RV diastolic function

OCT for observation of vasa vasorum

Background Hypoxia and low pulmonary arterial (PA) blood flow stimulate the development of systemic-to-pulmonary collateral blood vessels, which can be an adverse factor when performing the Fontan operation. The aim of this study was to use optical coherence tomography (OCT) to elucidate the morphological changes in PA vasculature after creation of a bidirectional cavopulmonary connection (BCPC) in children. Methods This prospective study evaluated PA wall thickness and development of PA vasa vasorum (VV) in the distal PA of eight patients (BCPC group, 1.3 ± 0.3 years) and 20 age-matched children with normal pulmonary artery hemodynamics and morphology (Control group, 1.4 ± 0.3 years). VV development was defined by the VV area ratio, defined as the VV area divided by the adventitial area in cross-sectional images. Results There was no significant difference in PA wall thickness between the BCPC and control groups (0.12 ± 0.03 mm vs. 0.12 ± 0.02 mm, respectively). The VV area ratio was significantly greater in the BCPC group than in the Control group (14.5 ± 3.5% vs. 5.3 ± 1.6%, respectively; p<0.0001). Conclusion OCT is a promising new tool for evaluating PA pathology, including the development of VV in patients after BCPC

RV Stiffness and Relaxation in PAH

We hypothesized that the kinematic model-based parameters obtained from the transtricuspid E-wave would be useful for evaluating RV diastolic property in pediatric pulmonary arterial hypertension (PAH) patients. The model was parametrized by stiffness/elastic recoil k, relaxation/damping c, and load x. These parameters were determined as the solution of m⋅d2x/dt2 + c⋅dx/dt + kx = 0, which is based on the theory that the E-wave contour is determined by the interplay of stiffness/restoring force, damping/relaxation force, and load. The PAH group had a significantly higher k and c versus the control group (182.5 ± 72.4 g/s2 vs. 135.7 ± 49.5 g/s2, p = 0.0232 and 21.9 ± 6.5 g/s vs. 10.6 ± 5.2 g/s, p <0.0001, respectively). These results show that RV has a higher stiffness/elastic recoil and inferior cross-bridge relaxation in the PAH group. Present findings indicate the feasibility and utility of kinematic model parameters for assessing RV diastolic function

A novel index equivalent to the myocardial performance index for right ventricular functional assessment in children and adolescent patients

The aims of the present study were to develop and check the utility and feasibility of a novel right ventricular (RV) functional index (RV angular velocity; RVω, s−1) derived from the angular velocity in harmonic oscillator kinematics obtained from the RV pressure waveform. We hypothesized that RVω reflects the myocardial performance index (MPI), which represents global RV function. A total of 132 consecutive patients, ranging in age from 3 months to 34 years with various cardiac diseases were included in this prospective study. RVω was defined as the difference between the peak derivative of pressure (dP/dt_max − dP/dt_min) divided by the difference between the maximum and minimum pressure (Pmax – Pmin). RVω showed significant negative correlations with the pulsed-wave Dopplerderived myocardial performance index (PWD-MPI) and the tissue Doppler imaging-derived MPI (TDI-MPI) (r = −0.52 and −0.51, respectively; both p < 0.0001). RVω also showed significant positive correlations with RV fractional area change (RVFAC) and RV ejection fraction (RVEF) (r = 0.41 and 0.39, respectively; both p < 0.0001), as well as a significant negative correlation with tricuspid E/e′ (r = −0.19, p = 0.0283). The clinical feasibility and utility of RVω for assessing global RV performance, incorporating both systolic and diastolic function, were demonstrated

Pathophysiology and Functional Assessment of Right Heart Failure

In pediatric cardiology, many situations require analysis of right ventricular function, but accurate measurement and evaluation of right ventricular function are not easy. The pathophysiology of right heart failure involves three mechanisms: pressure overload, volume overload, and myocardial dysfunction. In practice, however, these mechanisms often overlap to varying degrees. The most frequent and important cause of right ventricular dysfunction is pulmonary hypertension. Assessment of right ventricular dysfunction due to pulmonary hypertension may serve not only as a prognostic factor in this disease, but also as a baseline study that can be applied and inferred in other diseases. Thus, assessment of right ventricular dysfunction in pressure overload can serve as a pivotal study for universal analysis of right ventricular behavior. In this review, we describe the structure and function of the normal right ventricle, followed by an explanation of the evaluation method of right ventricular dysfunction. We explain that right ventricular dysfunction includes not only changes in the contractile function of the right ventricle as a whole, but also impairments in contractile style, right ventricular-pulmonary coupling, synchrony, interventricular interaction, and diastolic capacity.小児循環器領域において右室機能解析を要する場面は多いが，正確な右室機能を測定評価することは簡単ではない．右心不全を呈する病態を分類すると，圧負荷，容量負荷，心筋障害の3つの機序が原因として挙げられるが，実際には様々な程度でこれらは混在することが多い．これらのうち右室機能障害の最も重要な原因は肺高血圧症であり，圧負荷に対する右室機能解析は同疾患の予後規定因子として評価が重要であるというだけではなく，右室機能障害を来す他疾患への応用と右室挙動の普遍的な解析のための基軸研究となり得る点で意義深い． 本総説では正常右室の構造・機能を解説したのち，右室機能障害の評価方法について説明する．右室機能障害は，右室全体の収縮機能の変化だけでなく，収縮様式，右室－肺動脈カップリング，同期性，心室間相互作用，拡張能などの障害も含んでいることを解説していく

The Action of Smooth Muscle Cell Potassium Channels in the Pathology of Pulmonary Arterial Hypertension

Many different types of potassium channels with various functions exist in pulmonary artery smooth muscle cells, contributing to many physiological actions and pathological conditions. The deep involvement of these channels in the onset and exacerbation of pulmonary arterial hypertension (PAH) also continues to be revealed. In 2013, KCNK3 (TASK1), which encodes a type of two-pore domain potassium channel, was shown to be a predisposing gene for PAH by genetic mutation, and it was added to the PAH classification at the Fifth World Symposium on Pulmonary Hypertension (Nice International Conference). Decreased expression and inhibited activity of voltage-gated potassium channels, particularly KCNA5 (Kv1.5), are also seen in PAH, regardless of the cause, and facilitation of pulmonary arterial contraction and vascular remodeling has been shown. The calcium-activated potassium channels seen in smooth muscle cells also change from BKca (Kca1.1) to IKca (Kca3.1) predominance in PAH due to transformation, and have effects including the facilitation of smooth muscle cell migration, enhancement of proliferation, and inhibition of apoptosis. Elucidation of these roles for potassium channels in pulmonary vasoconstriction and remodeling may help bring new therapeutic strategies into view

コドモ ノ シンゾウ オ MDCT デ ミル

Multidetector-row CT（MDCT）scanners are a widely available, accurate, and noninvasivetechnique for the diagnosis of cardiovascular disorders. In the present review, we showed theclinical application for the diagnosis of congenital heart disease. Our study demonstrated thefeasibility of MDCT in assessing pulmonary artery size and morphology. Virtual endoscopy usingMDCT enables evaluation of the inner space of the vessels. Furthermore, MDCT was useful forthe evaluation of prosthetic graft calcificatio