Bosentan, a dual endothelin receptor blocker, has been used clinically to treat idiopathic pulmonary arterial hypertension (IPAH). However, the mechanism of its antiproliferative effect on pulmonary artery smooth muscle cells (PASMCs) remains unclear. A rise in cytoplasmic Ca2+ stimulates PASMC proliferation and the canonical transient receptor potential (TRPC) channels are an important pathway for Ca2+ entry during PASMC proliferation. Bosentan (20-50 microM) significantly inhibited endothelin-1- or platelet-derived growth factor (PDGF)-mediated PASMC growth and [3H]thymidine uptake. In PASMCs, endothelin-1 (1 microM) and PDGF (10 ng/ml) both upregulated protein expression of TRPC6, whereas bosentan markedly downregulated TRPC6 protein levels. Furthermore, TRPC6 expression in PASMCs from patients with IPAH was greater than in normal PASMCs, and the antiproliferative effect of bosentan was significantly enhanced in IPAH-PASMCs in comparison with normal PASMCs. These observations demonstrate that the antiproliferative effect of bosentan on PASMCs involves the downregulation of TRPC6 channels via a mechanism possibly independent of endothelin receptor blockade. The greater effect of bosentan on IPAH-PASMCs than on normal PASMCs suggests that increased TRPC6 expression and function may be involved in the overgrowth of PASMCs in patients with IPAH.

As demonstrated by QMCE, GPI improves microvascular flow and reduces the infarct area after coronary occlusion/reperfusion, independent of epicardial flow. These data demonstrate the usefulness of QMCE in assessing microvascular flow, provide novel evidence for the role of platelets in the early phase of reperfusion injury, and show that GPI is of value in preserving microvascular perfusion after coronary reperfusion.

he left ventricular (LV) myocardium consists of obliquely oriented muscle fibers that vary from a right-handed helix at the endocardium (Endo) to a left-handed helix at the epicardium (Epi), with most myofibers in approximately circumferential orientation. 1 This 3-dimensional myocardial structure results in rotation of the LV apex with respect to the base, which accompanies contraction and relaxation, and this LV rotational deformation is thought to generate LV torsion while also equalizing fiber stress and sarcomere length across the LV wall. 2 Many methods have been used to describe and quantify LV torsion, including cineangiography with radioopaque markers, 3-7 magnetic resonance imaging (MRI) 8-11 and 2-Circulation Journal Vol.71, May 2007 dimensional (2D) echocardiography. [12][13][14] The cineangiography technique requires implantation at the time of cardiac operation, thus limiting the population available for the study of LV torsion to patients with significant cardiac disease. MRI using myocardial tagging remains expensive and its temporal resolution is not sufficient to assess the time course of LV torsion in detail. 2D echocardiography is limited to measuring the rotation of a small number of identifiable structures such as the papillary muscles.We have developed a 2D echocardiographic tissue tracking system (2DTT) for tracking the locus of the LV myocardium to calculate myocardial strain without Doppler angle dependency. [15][16][17] The technique is based on a patternmatching algorithm, which enables tracking of selected points automatically during the whole cardiac cycle using digital image files.Using 2DTT, we tried to assess LV rotational deformation by calculating the rotation angles between the apex and base of the LV. 18-20 LV torsion of the Endo has been previously reported to be greater than that of the Epi according to tagged MRI analyses, [8][9][10] which suggests that shear occurs between the Endo and Epi (circumferentialradial shear) and this may play an important role in systolic Circ J 2007; 71: 661 -668 (Received December 4, 2006; revised manuscript received January 17, 2007; accepted January 29, 2007 Background The difference in the left ventricular (LV) torsion of the endo-and epicardium (Endo, Epi) with inotropic stimulation and its relation to radial strain (RS) remain unclear. Methods and Results LV basal and apical short-axis images were recorded in 13 normal subjects at rest and during dobutamine infusion (5, 10 g·kg -1 ·min -1 ). A total of 8 points (anterior, lateral, posterior and septum in both Endo and Epi) were manually placed by 2-dimensional tissue tracking technique and the movement of these points during a cardiac cycle was tracked, after which the rotation angles and RS were calculated. LV torsion was defined as the net difference between the basal and apical rotations. In the LV apex, Endo-rotation increased (7.8±2.7 to 14.1±4.6 degrees, p<0.01), whereas Epi-rotation was unchanged, with dobutamine. The apical Endorotation was significantly greater than the Ep...

he early diastolic velocity of the mitral annulus (Ea) obtained by tissue Doppler imaging (TDI) has been shown to be a preload-independent index for evaluating left ventricular (LV) diastolic function in patients with heart disease. 1,2 When TDI is combined with pulsedDoppler transmitral flow in early diastole (E), the resultant E/Ea ratio has correlated with LV filling pressures measured invasively. [2][3][4][5][6] Several researchers have assessed the lateral mitral annulus, 2,4,6 stating that lateral annular velocities were slightly higher than septal annular velocities and were often easier to quantify, 2 whereas other researchers have successfully used the septal mitral annulus. 3 It is known that cardiac surgery reflects the LV diastolic property and that LV diastolic function after cardiac surgery is 1 of the predictors of the long-term prognosis of patients undergoing cardiac surgery. 7 Although mitral annular velocities are widely used for evaluating LV diastolic function, it is unknown whether the lateral or septal mitral annular velocity more faithfully predicts LV filling pressures after cardiac surgery. We hypothesized that cardiac surgery affects the predictive values for LV filling pressures by measuring mitral annular velocity. The aims of this study were (1) to critically evaluate the usefulness and limitations of TDI for the evaluation of diastolic filling in patients undergoing cardiac surgery and (2) to compare the TDI results of the lateral and septal mitral annulus for the assessment of LV filling pressures, both before and after surgery. Methods Study PopulationWe studied 52 consecutive patients undergoing cardiac surgery. All patients were in sinus rhythm and had a normal PQ interval on ECG. Exclusion criteria were atrial fibrillation, paced rhythm, mitral stenosis, severe mitral or aortic regurgitation, acute myocardial infarction, or previous cardiac surgery. All patients underwent transthoracic echocardiography and right-sided cardiac catheterization both before and after surgery. None of the patients showed abnormalities on ECG or cardiac enzyme elevation during the perioperative period. The institutional review boards of Yamaguchi University Hospital approved the investigational protocol, and all patients gave written informed consent before participation. EchocardiographyAll patients were examined by transthoracic echocardio- Background Although previous investigators reported that mitral annular velocity predicts mean pulmonary capillary wedge pressure (PCWP), it is unknown whether the lateral or septal mitral annular velocity more faithfully predicts PCWP after cardiac surgery. Methods and ResultsTo assess the effect of cardiac surgery on the predictive values for PCWP by measuring mitral annular velocity, 52 consecutive patients undergoing cardiac surgery were studied. All patients underwent transthoracic echocardiography and right-sided cardiac catheterization both before and after surgery. The peak early diastolic velocity of transmitral flow (E) was measured by pulsed-wave D...

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