Patterns of regional diastolic function in the normal human left ventricle: An ultrafast computed tomographic study

AbstractThe detailed evaluation of regional diastolic filling at multiple ventricular levels in the normal human left ventricle has not previously been reported. Ultrafast computed tomography was used to characterize global and regional early diastolic filling in the left ventricle of 11 normal male volunteers. Regional early diastolic filling data from six distinct ventricular levels (apex to base) were fit to a third-order polynomial curve, and the peak rate of diastolic filling and time of peak filling were determined. Peak filling rate was 259 ± 17 ml/s (±SEM) as a global average, where peak filling rate referenced to end-diastolic volume and stroke volume across the levels examined was 3.78 ± 0.17 s−and 4.83 ± 0.20 s−respectively. Average filling fraction was 39 ± I%, and time to peak filling from end-systole was 145 ± 5 ms.Regional (tomographic) peak filling rates, except for the most apical level examined, were not statistically different across the ventricle. Filling fraction and time to peak filling were remarkably constant from one level to another. However, reference of regional peak filling rate to regional end-diastolic volume demonstrated significant nonuniformity from apex (120% of average for all levels) to base (87% of average for all levels). Peak filling rate referenced to tomographic stroke volume was less variable and not statistically different across the ventricle as a whole.In conclusion, values of regional absolute early peak diastolic ventricular filling rate or values normalized for regional end-diastolic volume are characteristically nonuniform across the left ventricle, whereas other variables such as filling fraction, time to peak filling and regional peak filling rate referenced to regional stroke volume are highly uniform. This confirms an intimate relation between rates of regional diastolic filling and regional ventricular size and stroke volume in the normal human heart

Ultrafast Computed Tomography Analysis of Regional Radius-to-Wall Thickness Ratios in Normal and Volume-Overloaded Human Left Ventricle

Ultrafast computed tomography analysis of regional radius-to-wall thickness ratios in normal and volume-overloaded human left ventricl

Thiazolides as novel antiviral agents. 2. Inhibition of Hepatitis C virus replication

We report the activities of a number of thiazolides [2-hydroxyaroyl-N-(thiazol-2-yl)amides] against hepatitis C virus (HCV) genotypes IA and IB, using replicon assays. The structure–activity relationships (SARs) of thiazolides against HCV are less predictable than against hepatitis B virus (HBV), though an electron-withdrawing group at C(5′) generally correlates with potency. Among the related salicyloylanilides, the m-fluorophenyl analogue was most promising; niclosamide and close analogues suffered from very low solubility and bioavailability. Nitazoxanide (NTZ) 1 has performed well in clinical trials against HCV. We show here that the 5′-Cl analogue 4 has closely comparable in vitro activity and a good cell safety index. By use of support vector analysis, a quantitative structure–activity relationship (QSAR) model was obtained, showing good predictive models for cell safety. We conclude by updating the mode of action of the thiazolides and explain the candidate selection that has led to compound 4 entering preclinical development