The utility of considering right ventricular (RV) contractility and afterload as independent entities and summarising their balance or "coupling" using single beat methods has become widely appreciated [1][2][3]. Typically expressed as the ratio of end-systolic ventricular elastance (Ees, a load-independent measure of contractility), to arterial elastance (Ea, a lumped parameter measure of afterload) data suggest that when Ees/Ea reaches a critical threshold, the risk of cardiovascular decompensation begins to rise [4].Pressure-based single beat methods have two central features: prediction of Pmax, the theoretical pressure generated within the RV if contraction remained isovolumic, and definition of end-systolic pressure (ESP). These variables are then used to calculate Ees as (Pmax−ESP)/SV, and Ea as ESP/SV, where SV is the stroke volume. However, it remains unclear what a "normal" RV Ees/Ea value is, due in part to variation in how ESP is defined [5,6], a consideration highlighted in a recent clinical study comparing single and multi-beat determination of Ees/Ea [7]. Additionally, directly relating Ees/Ea to right ventricular ejection fraction (RVEF), a variable clinicians are more familiar with, is challenging. RVEF has been repeatedly shown to predict outcomes in patients with severe pulmonary hypertension (PH) [8], and while cardiac magnetic resonance imaging (cMRI) or three-dimensional echocardiography allow for direct measurement of RVEF, they are not routinely used for repeated measurement of RVEF during a clinically indicated right heart study. The present proof of concept study was designed to test the hypothesis that a method using readily available software and based entirely on analysis of the right ventricular pressure (RVP) waveform can effectively track acute changes in RVEF.Archived measurements of RVP and RV volume provided by conductance/micromanometer catheter were retrospectively analysed. Data had been acquired from 15 anaesthetised swine (∼55 kg) under Institutional Animal Care and Use Committee-approved protocols and in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Prospective clinical data were acquired under a protocol approved by the Yale Human Investigation Committee. Input signals were sampled at 200 Hz and measured reference values for RVEF calculated from beat-to-beat RV volume as SV/end-diastolic volume. Experimental data had been recorded before and during interventions to alter RV afterload alone or in combination with inotropic depression or augmentation.The Dynamic Fit Wizard within SigmaPlot (version 13, Systat Software, Inc., San Jose, CA) was used to predict Pmax with a distribution function (the 4 parameter Weibull peak fit). In a pilot study involving 15 RVP waveforms with peak pressures ranging from ∼20 to 50 mmHg, the distribution function was found to yield Pmax values that were within 3±7 mmHg of those derived using a more conventional sinusoidal function (figure 1a). For ejection fraction estimation, an alternativ...

orb is a founding member of the CPEB family of translational regulators and is required at multiple steps during Drosophila oogenesis. Previous studies showed that orb is required during mid-oogenesis for the translation of the posterior/germline determinant oskar mRNA and the dorsal-ventral determinant gurken mRNA. Here, we report that orb also functions upstream of these axes determinants in the polarization of the microtubule network (MT). Prior to oskar and gurken translational activation, the oocyte MT network is repolarized. The MT organizing center at the oocyte posterior is disassembled, and a new MT network is established at the oocyte anterior. Repolarization depends upon cross-regulatory interactions between anterior (apical) and posterior (basal) Par proteins. We show that repolarization of the oocyte also requires orb and that orb is needed for the proper functioning of the Par proteins. orb interacts genetically with aPKC and cdc42 and in egg chambers compromised for orb activity, Par-1 and aPKC protein and aPKC mRNA are mislocalized. Moreover, like cdc42-, the defects in Par protein localization appear to be connected to abnormalities in the cortical actin cytoskeleton. These abnormalities also disrupt the localization of the spectraplakin Shot and the microtubule minus-end binding protein Patronin. These two proteins play a critical role in the repolarization of the MT network.

Background: Experimental studies of pulmonary hypertension (PH) in rodents commonly focus upon right ventricular systolic pressure (RVSP) and Fulton Index to quantify disease severity. While RV ejection fraction (RVEF) can also be measured in vivo with echocardiography or catheter-based measurement of intracardiac volume, widespread application is limited by cost and technical limitations. Nonetheless, in humans with PH, RVEF has prognostic significance suggesting value of the measure in experimental models. The present study was designed to test the hypothesis that a relatively simple method based entirely upon analysis of the RV pressure waveform can accurately estimate RVEF over the range evident in normal and PH animals. Methods: RV pressure and volume data sampled at 1000 Hz and acquired under IACUC-approved protocols from 15 rats (7 controls, 8 sugen/hypoxia PH) were used. Data had been recorded during isoflurane anesthesia and mechanical ventilation with a Millar Aria 1 PV System linked to an ADI Powerlab and a 1.4-F Millar conductance catheter introduced into the RV long axis via apical puncture. The volume signal was calibrated using the cuvette method and measured reference values for RVEF (EFmeas) calculated as stroke volume/end-diastolic volume. From the pressure signal, RVEF was estimated (EFest) as (Pmax-ESP)/Pmax where Pmax = the predicted RV pressure that would have been achieved if ejection did not occur, and ESP = end-systolic pressure defined from an event marker based upon the second derivative of RV pressure (figure 1A). Method comparison procedures were applied to describe correlation, accuracy (bias), and precision (limits of agreement or LOA). EFest was considered potentially interchangeable with EFmeas if the bias was <10% of the mean of all data and overall error (SD of the bias x 1.96/the mean of all EF values) was <30%. Results: Across the dataset, RVSP ranged from 22 to 96 mmHg and EFmeas from 0.19 to 0.60. Method comparison data (figure 1 B and C) demonstrate strong correlation between EFmeas and EFest (r 2 = 0.813, p< 0.0001), a bias of -0.02 (4% of mean) with LOA from -0.11 to 0.08, and an overall error of 20%. Conclusions: The study results demonstrate that when compared to RVEF directly measured by intraventricular conductance catheter in normal and PH rats, the pressure-based method provides RVEF estimates with a high degree of correlation, minimal bias, and modest error. These data suggest potential utility for RVEF estimation as an adjunct to RVSP in rat models of PH.

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