Impact of changes in heart rate and stroke volume on the cross sectional flow velocity distribution of diastolic mitral blood flow

The effect of changes in stroke volume on the cross sectional velocity distribution in the mitral orifice during passive mitral inflow was studied in six patients with total atrioventricular block, atrial fibrillation and VVI pacemakers during periods with different heart rates. The time velocity integrals recorded both in the left ventricular outflow tract and at the mitral orifice decreased significantly as the heart rate was increased from 60 to 80 and from 80 to 100 beats per minute. Instantaneous cross sectional flow velocity profiles were constructed by time interpolation of the velocity data from each point in sequentially delayed two dimensional digital ultrasound maps. Each patient had a characteristic cross sectional flow velocity profile in the mitral orifice recorded at the level of the leaflet tips in a four chamber view. The velocity profiles varied between the patients. With increase in heart rate only minimal changes in the flow profiles from individual patients were seen. The maximum velocity through the mitral orifice overestimated the cross sectional mean velocity at the same time by a factor of 1.4–1.9. The maximum time velocity integral overestimated the cross sectional mean by a factor of 1.4–1.8. The observed cross sectional skew varied between patients but did not change significantly with increasing heart rate and decrease in stroke volume.     

A peptide agonist of the neural cell adhesion molecule (NCAM), C3, protects against developmental defects induced by a teratogen pyrimethamine.

The neural cell adhesion molecule, NCAM, not only plays an important role in neuronal migration, differentiation and formation of connections in the developing nervous system, but also in the condensation of the mesodermal mesenchyme of the limb bud. Therefore, NCAM may be regarded as a target molecule for preventive strategies aimed at minimizing the effects of teratogens affecting the prenatal development of the nervous system and the skeleton. Treatment of fetuses with the teratogen pyrimethamine results in a reduced body weight, microcephaly and malformations of the hind limbs and forelimbs, e.g. micromelia, brachydactyly and adactyly. We here show that a peptide agonist of NCAM, C3, partly prevented the defects induced by this treatment. Although intra-amniotic administration of C3 at gestational day 14 had no effect on the pyrimethamine-induced reduction in body weight, it rescued the deficit in brain weight (microcephaly), partly reversed a decrease in thickness of the cortical plate, and significantly reduced the number of malformed fetuses. In vitro, C3 promoted survival of PC12-E2 cells treated with pyrimethamine. Since C3 is a peptide mimetic of NCAM, our data strongly suggest that stimulating of NCAM results in neuroprotection in vivo and in vitro.     

Instantaneous cross-sectional flow velocity profiles: a comparative study of two ultrasound Doppler methods applied to an in vitro pulsatile flow model

Two methods based on different techniques for construction of cross-sectional flow velocity profiles from Doppler ultrasound signals were compared: an intraluminal method using pulsed-wave Doppler echocardiography and an extraluminal method using two-dimensional (color) Doppler ultrasound. The methods were applied to an in vitro pulsatile flow model. With the intraluminal method, pulsed Doppler recordings obtained throughout several flow pulses at different positions across a tube were digitized, and cross-sectional flow velocity profiles were obtained by matching the onset of flow velocity at the various positions. With the extraluminal method, cross-sectional flow velocity profiles were obtained by time interpolation between the digital flow velocity data obtained from several flow velocity maps. The first flow velocity map was recorded at onset of flow and the following maps were incrementally delayed with 20 msec from one flow pulse to the next. The time lag caused by the time needed to update each of the flow velocity maps was compensated for by time interpolation between the sequentially recorded flow velocity maps. The cross-sectional flow velocity profiles obtained with the two methods were compared at identical positions within the tube model at equal flow settings and throughout the pulsatile flow periods. At three different flow settings with peak flow velocity of 0.3, 0.5, and 0.7 m/sec, the difference (mean +/- SD) between the obtained velocities were 0.01 +/- 0.04, -0.01 +/- 0.05, and -0.03 +/- 0.07 m/sec, respectively. The findings suggest that cross-sectional flow velocity profiles from pulsatile flow velocity recordings can be obtained equally well with both methods.     

A semiautomated objective technique for applying the proximal isovelocity surface area method to quantitate mitral regurgitation: Clinical studies with the digital flow map

BACKGROUND: Clinical application of the color Doppler proximal isovelocity surface area (PISA) method to quantify mitral regurgitation (MR) has been limited by the often inaccurate assumption that isovelocity surfaces are hemispheric. This study applied an objective method for selecting the region where the hemispheric geometry holds best on the basis of mathematic analysis of results at different distances from the orifice. We aimed to demonstrate this approach can be applied accurately in the clinical setting and can be semiautomated to promote routine use by extracting velocities from the digital Doppler output and then performing all the calculations automatically. METHODS: In 75 patients with isolated MR, centerline velocities (V(r)) at each distance (r) from the orifice in the proximal flow field were extracted digitally. The automated analysis calculated peak MR flow rates as 2pir(2)V(r) and plotted these against their respective velocities. The optimal value for peak flow rate was obtained mathematically at the site where the slope of this curve was minimal (least inaccuracy). This value was combined with continuous wave Doppler data to provide regurgitant stroke volume (RSV) and orifice area (ROA), which were compared with quantitative Doppler in 75 patients and angiography in 42. RESULTS: RSV and ROA by this optimized, semiautomated PISA method correlated and agreed well with values from quantitative Doppler (y = 0.9x + 1.9, r = 0.90, standard error of the estimate [SEE] = 8.1 mL, mean difference = -0.7 +/- 8.5 mL for RSV; y = 0.9x + 0.02, r = 0.90, SEE = 0.048 cm(2), mean difference = -0.005 +/- 0.1 cm(2) for ROA) and correlated well with angiography (rho = 0.90 for both RSV and ROA). CONCLUSIONS: This objective PISA method for quantifying MR is accurate in the clinical setting and has been semiautomated by use of analysis of digital velocity data to provide a rapid and practical technique suitable to facilitate more extensive application in routine practice.