Introduction Coarctation of the aorta (CoA) is associated with morbidity despite treatment. Although mechanisms remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We present a novel approach that facilitates quantification of coarctation-induced mechanical alterations and their impact on vascular structure and function, without genetic or confounding factors. Methods Rabbits underwent thoracic CoA at 10 weeks of age ( ~9 human years) to induce a 20 mmHg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using imaging and BP data at 32 weeks to quantify velocity, strain and wall shear stress (WSS) for comparison to vascular structure and function as revealed by histology and myograph results. Results Systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular thickening, disorganization and endothelial dysfunction proximally and distally. Corrected rabbits had less severe medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12 weeks of normal BP (~4 human years) after the suture dissolved. WSS was elevated distally for CoA rabbits, but reduced for corrected rabbits. Discussion These findings are consistent with alterations in humans. We are now poised to investigate mechanical contributions to mechanisms of morbidity in CoA using these methods.

Stamen hair cells of the spiderwort plant Tradescantia virginiana exhibit unusually predictable rates of progression through mitosis, particularly from the time of nuclear envelope breakdown (NEBD) through the initiation of cytokinesis. The predictable rate of progression through prometaphase and metaphase has made these cells a useful model system for the determination of the timing of regulatory events that trigger entry into anaphase. A number of studies suggest that the elevation of one or more protein kinase activities is a necessary prerequisite for entry into anaphase. The current experiments employ two strategies to test when these elevations in protein kinase activity actually occur during metaphase. In perfusions, we added the protein kinase inhibitors K-252a, staurosporine, or calphostin C to living stamen hair cells for 10-min intervals at known times during prometaphase or metaphase and monitored the subsequent rate of progression into anaphase. Metaphase transit times were altered as a function of the time of addition of K-252a or staurosporine to the cells; metaphase transit times were extended significantly by treatments initiated in prometaphase through early metaphase and again late in metaphase. Transit times were normal after treatments initiated in mid-metaphase, approximately 15 to 21 min after NEBD. Calphostin C had no significant effect on the metaphase transit times. In parallel, cells were microinjected with known quantities of a general-purpose protein kinase substrate peptide, VRKRTLRRL, at predefined time points during prometaphase and metaphase. At a cytosolic concentration of 100 nM to 1 microM, the peptide doubled or tripled the metaphase transit times when injected into the cytosol of mitotic cells within the first 4 min after NEBD, at any point from 7.5 to 9 min after NEBD, at any point from 14 to 16 min after NEBD, at 21 min after NEBD, or at 24 min after NEBD. At the concentration used and during these brief intervals, the peptide appeared to act as a competitive inhibitor to reveal inflection points when protein kinase activation was occurring or when endogenous substrate levels approached levels of the peptide. The timing of these inflection points coincides with the changes in protein kinase activities during prometaphase and metaphase, as indicated by our perfusions of cells with the broad spectrum kinase inhibitors. Collectively, our results suggest that the cascade that culminates in anaphase is complex and involves several successive protein kinase activation steps punctuated by the activation of one or more protein phosphatases in mid-metaphase.

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Background: For more than 10 years cardiovascular magnetic resonance (CMR) has been applied as the diagnostic tool in the measurement of left ventricular (LV) volumes, function, and mass .The superb accuracy and reproducibility of CMR is well established making it a gold standard modality. Right ventricular (RV) parameters have a promising prognosticator in cardiovascular mortality and morbidity; nevertheless it has been less investigated as compared to LV. The purpose of this study was sought to assess the prevalence of RV dysfunction (defined as RVEF <40%) in LV dysfunction patients (determined by LVEF <40%) and its predictors.Methods: A total of 280 patients with LV dysfunction referring for CMR were consecutively enrolled (66.1% male, mean age 65.3+12.5 years). Assessment for RV end-diastolic volume, end-systolic volume, myocardial mass, and RV ejection fraction were performed. The predictors for impaired RV systolic function were then analysed.Results: Mean LVEF was 25.9 + 8.5%. RV dysfunction was found in 125 patients (44.6%). Using univariate analysis, age, New York Heart functional class, LVEF, LVEDV, LVESV and late gadolinium enhancement were significant predictors for RV dysfunction. By multivariate analysis, only age, New York Heart functional class and LVEF remained significant (p 0.03, p 0.02 and p 0.001, respectively).Conclusions: The prevalence of RV dysfunction in the patients with LV systolic dysfunction was as high as 44.6%. Age, New York Heart functional class and LVEF were the independent predictors of RV dysfunction. Prognostic value of RV dysfunction in patients with cardiomyopathies warrant further studies. Methods: We consecutively reviewed 314 MPS and 221 CTCA studies performed at our hospital in 2013. Stress/ Rest MPS studies were performed with exercise and/or adenosine using Sestamibi Tc 99m and a solid state Cadmium Zinc Telluride gamma camera. CTCA was performed using a 256 slice CT. Radiation exposure was measured in milisievert (mSv). Positive tests leading to invasive coronary angiography were used to determine the PPV of the need for revascularisation.Results: For demographics see table 1. The main indication for tests in both cohorts was chest pain (>75%). Patients undergoing MPS were older, more likely to have diabetes, and had worse renal function compared with CTCA (p < 0.01).41/314 (13%) MPS and 26/221 (11%) CTCA patients proceeded to have coronary angiography. There was a small but statistically significant reduction in radiation dose for CTCA compared with MPS (p < 0.01). CTCA was significantly better at predicting the need for revascularisation compared with MPS (PPV 80% vs 51%, p: 0.02).Conclusions: Despite lower than usual dose MPS utilising contemporary techniques, radiation dose remained lower with CTCA. CTCA had a higher PPV of the need for revascularisation compared with MPS in our non-randomised evaluation.http://dx

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