Pulsatile shear stress leads to DNA fragmentation in human SH-SY5Y neuroblastoma cell line.
1. Using an in vitro model of shear stress-induced cell injury we demonstrate that application of shear to differentiated human SH-SY5Y cells leads to cell death characterized by DNA fragmentation. Controlled shear stress was applied to cells via a modified cone and plate viscometer. 2. We show that pulsatile shear stress leads to DNA fragmentation, as determined via flow cytometry of fluorescein-12-dUTP nick-end labelled cells, in 45 +/- 4 % of cells. No lactate dehydrogenase (LDH) release was observed immediately after injury; however, 24 h after injury significant LDH release was observed. 3. Nitric oxide production by cells subjected to pulsatile shear increased two- to threefold over that in unsheared control cells. 4. Inhibition of protein synthesis, nitric oxide production, Ca2+ entry into cells, and pertussis toxin-sensitive G protein activation attenuated the shear stress-induced cell injury. 5. Our results show for the first time that application of pulsatile shear stress to a neuron-like cell in vitro leads to nitric oxide-dependent cell death. (+info
Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction.
OBJECTIVES: The purpose of this study was to evaluate the relationship of baseline pulse pressure and mean arterial pressure to mortality in patients with left ventricular dysfunction. BACKGROUND: Increased conduit vessel stiffness increases pulse pressure and pulsatile load, potentially contributing to adverse outcomes in patients with left ventricular dysfunction. METHODS: Pulse and mean arterial pressure were analyzed for their effect on mortality, adjusting for other modifiers of risk, using Cox proportional hazards regression analysis of data collected from 6,781 patients randomized into the Studies of Left Ventricular Dysfunction trials. RESULTS: Pulse and mean arterial pressure were related positively to each other, age, ejection fraction and prevalence of diabetes and hypertension and inversely to prior myocardial infarction and beta-adrenergic blocking agent use. Higher pulse pressure was associated with increased prevalence of female gender, greater calcium channel blocking agent, digoxin and diuretic use, lower heart rate and a higher rate of reported smoking history. Higher mean arterial pressure was associated with higher heart rate, lower calcium channel blocker and digoxin use and lower New York Heart Association functional class. Over a 61-month follow-up 1,582 deaths (1,397 cardiovascular) occurred. In a multivariate analysis adjusting for the above covariates and treatment assignment, higher pulse pressure remained an independent predictor of total and cardiovascular mortality (total mortality relative risk, 1.05 per 10 mm Hg increment; 95% confidence interval, 1.01 to 1.10; p = 0.02). Mean arterial pressure was inversely related to total and cardiovascular mortality (total mortality relative risk, 0.89; 95% confidence interval, 0.85 to 0.94; p <0.0001). CONCLUSIONS: One noninvasive blood pressure measurement provides two independent prognostic factors for survival. Increased conduit vessel stiffness, as assessed by pulse pressure, may contribute to increased mortality in patients with left ventricular dysfunction, independent of mean arterial pressure. (+info
In vitro and in vivo comparison of three MR measurement methods for calculating vascular shear stress in the internal carotid artery.
BACKGROUND AND PURPOSE: Vascular abnormalities, such as atherosclerosis and the growth and rupture of cerebral aneurysms, result from a derangement in tissue metabolism and injury that are, in part, regulated by hemodynamic stress. The purpose of this study was to establish the feasibility and accuracy of determining wall shear rate in the internal carotid artery from phase-contrast MR data. METHODS: Three algorithms were used to generate shear rate estimates from both ungated and cardiac-gated 2D phase-contrast data. These algorithms were linear extrapolation (LE), linear estimation with correction for wall position (LE*), and quadratic extrapolation (QE). In vitro experiments were conducted by using a phantom under conditions of both nonpulsatile and pulsatile flow. The findings from five healthy volunteers were also studied. MR imaging-derived shear rates were compared with values calculated by solving the fluid flow equations. RESULTS: Findings of in vitro constant-flow experiments indicated that at one or two excitations, QE has the advantage of good accuracy and low variance. Results of in vitro pulsatile flow experiments showed that neither LE* nor QE differed significantly from the predicted value of wall shear stress, despite errors of 17% and 22%, respectively. In vivo data showed that QE did not differ significantly from the predicted value, whereas LE and LE* did. The percentages of errors for QE, LE, and LE* in vivo measurements were 98.5%, 28.5%, and 36.1%, respectively. The average residual of QE was low because the residuals were both above and below baseline whereas, on average, LE* tended to be a more biased overestimator of the shear rate in volunteers. The average and peak wall shear force in five volunteers was approximately 8.10 dyne/cm2 and 13.2 dyne/cm2, respectively. CONCLUSION: Our findings show that LE consistently underestimates the shear rate. Although LE* and QE may be used to estimate shear rate, errors of up to 36% should be expected because of variance above and below the true value for individual measurements. (+info
The pattern of changes in ovarian stromal and uterine artery blood flow velocities during in vitro fertilization treatment and its relationship with outcome of the cycle.
OBJECTIVES: To assess the effect of short-term (2-3 weeks) pituitary suppression and controlled ovarian stimulation on ovarian and uterine artery Doppler measurements during the in vitro fertilization (IVF) treatment cycle and to compare the pattern of these changes between conception and non-conception cycles as well as between patients with normal and those with polycystic ovaries. DESIGN: Prospective observational study of women undergoing IVF treatment. SUBJECTS: Women using the long-treatment buserelin protocol who did not have uterine fibroids, ovarian cysts or endometrioma. METHODS: Serial transvaginal color and pulsed Doppler measurements of ovarian stromal and uterine artery blood flow velocity were carried out in the early follicular phase of the menstrual cycle, on the day of pituitary suppression and on the day of administration of human chorionic gonadotropin (hCG). The main outcome measures were the ovarian stromal and uterine artery blood flow peak systolic velocity (PSV) and pulsatility index (PI). RESULTS: A total of 105 patients were recruited but six patients were excluded from the analysis because they had only one stage of the measurements performed. There was a significant decline in mean ovarian stromal artery PSV after 2-3 weeks of gonadotropin releasing hormone (GnRH) agonist therapy but no effect on ovarian stromal artery PI. The mean uterine artery PSV or PI did not change significantly after 2-3 weeks of GnRH agonist therapy. There was a significantly higher mean ovarian stromal artery PSV in conception cycles compared to non-conception cycles in the early follicular phase and on the day of pituitary suppression, but not on the day of hCG administration. There were no differences between conception and non-conception cycles in the mean uterine artery PSV or PI. Women with polycystic ovaries had a higher mean ovarian artery PSV on all the three occasions of measurement. CONCLUSION: These data suggest that assessment of ovarian blood flow before commencement of gonadotropin stimulation may play a role in assessing cycles likely to result in pregnancy. (+info
Characteristics of blood flow in intrauterine growth-restricted fetuses with hypercoiled cord.
OBJECTIVE: To clarify the characteristics of fetoplacental blood flow of growth-restricted fetuses with hypercoiled umbilical cord. SUBJECTS: Eight growth-restricted fetuses with hypercoiled cord. METHODS: Flow velocity waveforms of the umbilical cord artery and vein, fetal abdominal aorta and fetal inferior vena cava were analyzed. RESULTS: The resistance index in the umbilical artery in the hypercoiled cases was lower than that in normal fetuses. Early-diastolic reversed flow was observed in the abdominal aorta in some cases. In all cases, umbilical venous pulsation was observed in the entire cord until delivery. In one case, fetal heart failure occurred, resulting in pre-mature delivery. An atrophic type of single umbilical artery was observed in four cases. CONCLUSION: Fetal blood flow disturbance caused by a hypercoiled umbilical cord may be a cause of growth restriction. (+info
Pulmonary and caval flow dynamics after total cavopulmonary connection.
OBJECTIVE: To assess flow dynamics after total cavopulmonary connection (TCPC). DESIGN: Cross-sectional study. SETTING: Aarhus University Hospital. PATIENTS: Seven patients (mean age 9 (4-18) years) who had previously undergone a lateral tunnel TCPC mean 2 (0. 3-5) years earlier. INTERVENTIONS: Pressure recordings (cardiac catheterisation), flow volume, and temporal changes of flow in the lateral tunnel, superior vena cava, and right and left pulmonary arteries (magnetic resonance velocity mapping). RESULTS: Superior vena cava flow was similar to lateral tunnel flow (1.7 (0.6-1.9) v 1. 3 (0.9-2.4) l/min*m2) (NS), and right pulmonary artery flow was higher than left pulmonary artery flow (1.7 (0.6-4.3) v 1.1 (0.8-2. 5) l/min*m2, p < 0.05). The flow pulsatility index was highest in the lateral tunnel (2.0 (1.1-8.5)), lowest in the superior vena cava (0.8 (0.5-2.4)), and intermediate in the left and right pulmonary arteries (1.6 (0.9-2.0) and 1.2 (0.4-1.9), respectively). Flow and pressure waveforms were biphasic with maxima in atrial systole and late ventricular systole. CONCLUSIONS: Following a standard lateral tunnel TCPC, flow returning via the superior vena cava is not lower than flow returning via the inferior vena cava as otherwise seen in healthy subjects; flow distribution to the pulmonary arteries is optimal; and some pulsatility is preserved primarily in the lateral tunnel and the corresponding pulmonary artery. This study provides in vivo data for future in vitro and computer model studies. (+info
The effect of cold stress on uterine artery blood flow velocity waveforms in late pregnant women with and without preeclampsia.
Cold stimulus, immersing the hand into ice water, was given to pregnant women with and without preeclampsia. The uterine artery blood flow was observed before, during and after the stimulus by Doppler ultrasound. The pulsatility index in the uterine artery blood flow was significantly increased by the cold exposure in preeclampsia from 1.14 to 1.52, whereas it increased in normal control from 0.95 to 1.25. In two of 11 cases of preeclampsia with fetal growth restriction, cold stimulus to the mother elicited a decrease of variability on fetal heart rate monitoring. Cold stimulus induces the constriction of the uterine artery, leading to a decrease of placental blood flow. (+info
Transcranial color-coded duplex sonography of intracranial veins and sinuses in adults. Reference data from 130 volunteers.
BACKGROUND AND PURPOSE: Transcranial color-coded duplex sonography (TCCS) of intracranial veins and sinuses in adults is a new, emerging application of ultrasonographic imaging. This study reports a standardized examination protocol for venous TCCS and provides reference data for clinical application. METHODS: In 130 healthy volunteers (mean age, 45.9+/-16.9 years; range, 14 to 77 years) the intracranial venous system was examined using frequency-based transtemporal TCCS. Identification rate, blood flow velocity, resistance index, and systolic/diastolic ratio were recorded for each examined venous vessel. RESULTS: Intracranial veins and sinuses show a low pulsatile forward flow with maximal systolic blood flow velocity up to 20 cm/s. Significant side differences of blood flow velocity in the paired venous structures could not be detected. Venous flow velocities decreased with age, whereas resistance indices and systolic/diastolic ratios increased. Women showed higher flow velocities than men. Mean identification rates for all age groups ranged from 70% to 90% for the deep middle cerebral vein, the basal cerebral vein, and the great cerebral vein of Galen. The straight sinus, the transverse sinus, and the rostral part of the superior sagittal sinus could be detected in 55% to 70% of cases. Detection rates were dependent on age and decreased as age increased. CONCLUSIONS: Venous TCCS can reliably image a significant part of the cerebral venous system. This method can provide information on venous hemodynamics in normal subjects and pathological cases. (+info