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At least 109 records · Page 6

Computational Hemodynamics Involving Artificial Devices

This paper reports the progress being made towards developing complete blood flow simulation capability in human, especially, in the presence of artificial devices such as valves and ventricular assist devices. Devices modeling poses unique challenges different from computing the blood flow in natural hearts and arteries. There are many elements needed such as flow solvers, geometry modeling including flexible walls, moving boundary procedures and physiological characterization of blood. As a first step, computational technology developed for aerospace applications was extended in the recent past to the analysis and development of mechanical devices. The blood flow in these devices is practically incompressible and Newtonian, and thus various incompressible Navier-Stokes solution procedures can be selected depending on the choice of formulations, variables and numerical schemes. Two primitive variable formulations used are discussed as well as the overset grid approach to handle complex moving geometry. This procedure has been applied to several artificial devices. Among these, recent progress made in developing DeBakey axial flow blood pump will be presented from computational point of view. Computational and clinical issues will be discussed in detail as well as additional work needed.

Kwak, Dochan↗

Hemodynamic Responses to Head and Neck Cooling

Personal thermoregulatory systems which provide head and neck cooling are used in the industrial and aerospace environments to alleviate thermal stress. However, little information is available regarding the physiologic and circulatory changes produced by routine operation of these systems. The objective of this study was to measure the scalp temperature and circulatory responses during use of one commercially available thermal control system. The Life Support Systems, Inc. Mark VII portable cooling system and a liquid cooling helmet were used in this study. Two EEG electrodes and one skin temperature transducer were placed on the anterior midline of the scalp to measure the scalp blood and temperature. Blood flow was measured using a bipolar impedance rheograph. Ten subjects, seated in an upright position at normal room temperature, were tested at high, medium, moderate, moderate-low and low coolant temperatures. Scalp blood flow was recorded continuously using a computer data acquisition system with a sampling frequency of 200 Hz. Scalp temperature and cooling helmet Inlet temperature was logged periodically during the test period. This study quantifies the effect of head cooling upon scalp temperature and blood flow. These data may also be used to select operational specifications of the head cooling system for biomedical applications such as the treatment of migraine headaches, scalp cooling during chemotherapy, and cooling of multiple sclerosis patients.

Ku, Yu-Tsuan E.↗

Hemodynamic and Thermal Responses to Head and Neck Cooling in Men and Women

Personal cooling systems are used to alleviate symptoms of multiple sclerosis and to prevent increased core temperature during daily activities. Configurations of these systems include passive ice vests and circulating liquid cooling garments (LCGs) in the forms of vests, cooling caps and combined head and neck cooling systems. However, little information is available oil the amount or heat that can be extracted from the body with these systems or the physiologic changes produced by routine operation of these systems. The objective of this study was to determine the operating characteristics and the physiologic change, produced by short term use of one commercially available thermal control system.

Ku, Yu-Tsuan E.↗

Non-invasive characterization of complex coronary lesions

Conventional invasive diagnostic imaging techniques do not adequately resolve complex Type B and C coronary lesions, which present unique challenges, require personalized treatment and result in worsened patient outcomes. These lesions are often excluded from large-scale non-invasive clinical trials and there does not exist a validated approach to characterize hemodynamic quantities and guide percutaneous intervention for such lesions. This work identifies key biomarkers that differentiate complex Type B and C lesions from simple Type A lesions by introducing and validating a coronary angiography-based computational fluid dynamic (CFD-CA) framework for intracoronary assessment in complex lesions at ultrahigh resolution. Among 14 patients selected in this study, 7 patients with Type B and C lesions were included in the complex lesion group including ostial, bifurcation, serial lesions and lesion where flow was supplied by collateral bed. Simple lesion group included 7 patients with lesions that were discrete, <10mm long and readily accessible. Intracoronary assessment was performed using CFD-CA framework and validated by comparing to clinically measured pressure-based index, such as FFR. Local pressure, endothelial shear stress (ESS) and velocity profiles were derived for all patients. We validates the accuracy of our CFD-CA framework and report excellent agreement with invasive measurements (n=14,R 2 =0.6,p=0.0013). Ultra-high resolution achieved by the model enable physiological assessment in complex lesions and quantify hemodynamic metrics in all vessels up to 1mm in diameter. Importantly, we demonstrate that in contrast to traditional pressure-based metrics, there is a significant difference in the intracoronary hemodynamic forces, such as ESS, in complex lesions compared to simple lesions at both resting and hyperemic physiological states [n = 14, p=0.03]. Higher ESS was observed in the complex lesion group (7.0±4.7 Pa) than in simple lesion group (4.8±3.6 Pa). Complex coronary lesions have higher ESS compared to simple lesions, such differential hemodynamic evaluation can provide much the needed insight into the increase in adverse outcomes for such patients and has incremental prognostic value over traditional pressure-based indices, such as FFR.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Temazepam, but not zolpidem, causes orthostatic hypotension in astronauts after spaceflight

Insomnia is a common symptom, not only in the adult population but also in many astronauts. Hypnotics, such as temazepam (a benzodiazepine) and zolpidem (an imidazopyridine), are often taken to relieve insomnia. Temazepam has been shown clinically to have hemodynamic side effects, particularly in the elderly; however, the mechanism is not clear. Zolpidem does not cause hemodynamic side effects. The purpose of this study was to determine whether the use of different hypnotics during spaceflight might contribute significantly to the high incidence of postflight orthostatic hypotension, and to compare the findings in astronauts with clinical research. Astronauts were separated into three groups: control (n = 40), temazepam (15 or 30 mg; n = 9), and zolpidem (5 or 10 mg; n = 8). In this study, temazepam and zolpidem were only taken the night before landing. The systolic and diastolic blood pressures and heart rates of the astronauts were measured during stand tests before spaceflight and on landing day. On landing day, systolic pressure decreased significantly and heart rate increased significantly in the temazepam group, but not in the control group or in the zolpidem group. Temazepam may aggravate orthostatic hypotension after spaceflight when astronauts are hemodynamically compromised. Temazepam should not be the initial choice as a sleeping aid for astronauts. These results in astronauts may help to explain the hemodynamic side effects in the elderly who are also compromised. Zolpidem may be a better choice as a sleeping aid in these populations.

STS Shuttle Project↗

Cerebral blood flow velocity declines before arterial pressure in patients with orthostatic vasovagal presyncope

OBJECTIVES: We studied hemodynamic changes leading to orthostatic vasovagal presyncope to determine whether changes of cerebral artery blood flow velocity precede or follow reductions of arterial pressure. BACKGROUND: Some evidence suggests that disordered cerebral autoregulation contributes to the occurrence of orthostatic vasovagal syncope. We studied cerebral hemodynamics with transcranial Doppler recordings, and we closely examined the temporal sequence of changes of cerebral artery blood flow velocity and systemic arterial pressure in 15 patients who did or did not faint during passive 70 degrees head-up tilt. METHODS: We recorded photoplethysmographic arterial pressure, RR intervals (electrocardiogram) and middle cerebral artery blood flow velocities (mean, total, mean/RR interval; Gosling's pulsatility index; and cerebrovascular resistance [mean cerebral velocity/mean arterial pressure, MAP]). RESULTS: Eight men developed presyncope, and six men and one woman did not. Presyncopal patients reported light-headedness, diaphoresis, or a sensation of fatigue 155 s (range: 25 to 414 s) before any cerebral or systemic hemodynamic change. Average cerebral blood flow velocity (CBFV) changes (defined by an iterative linear regression algorithm) began 67 s (range: 9 to 198 s) before reductions of MAP. Cerebral and systemic hemodynamic measurements remained constant in nonsyncopal patients. CONCLUSIONS: Presyncopal symptoms and CBFV changes precede arterial pressure reductions in patients with orthostatic vasovagal syncope. Therefore, changes of cerebrovascular regulation may contribute to the occurrence of vasovagal reactions.

Non-NASA Center↗

Pharmacokinetics of Acetaminophen in Hind Limbs Unloaded Mice: A Model System Simulating the Effects of Low Gravity on Astronauts in Space

The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in Space. Low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration in astronauts. Acquiring of such knowledge has inherent difficulties due to limited opportunities for experimenting in Space. One of the approaches is to use model systems that simulate some of the Space conditions on Earth. In this study we used hind limbs unloaded mice (HLU) to investigate the possible changes in PK of acetaminophen, a widely used analgesic with high probability of use by astronauts. The HLU is recognized as an appropriate model for simulating the effects of low gravity on hemodynamic parameters. Mice were tail suspended (n = 24) for 24-96 hours prior to introduction of acetaminophen (150 - 300 mg/kg). The drug (in aqueous solution containing 10% ethyl alcohol by volume) was given orally by a gavage procedure and after the administration of acetaminophen mice were additionally suspended for 30 min, 1 and 2 hours. Control mice (n = 24) received the same dose of acetaminophen and were kept freely all the time. Blood specimens were obtained either from retroorbital venous sinuses or from heart. Acetaminophen concentration was measured in plasma by the fluorescent polarization immunoassay and the AxSYM analyzer (Abbott Laboratories). In control mice peak acetaminophen concentration was achieved at 30 min. By 1 hour the concentration decreased to less than 50% of the peak level and at 2 hours the drug was almost undetectable in the serum. HLU for 24 hours significantly altered the acetaminophen pharmacokinetic: at 30 min the acetaminophen concentrations were significantly (both statistically and medically significant) lower than in control mice. The concentrations also reduced less significantly after 1 and 2 hours. At 2 hours approximately 20% of the drug still remained in the circulation. After 96 hrs of HLU the changes in acetaminophen PK were less prominent. These data indicate that short term HLU causes significant changes in acetaminophen PK most likely associated with HUL-related hemodynamic changes. However, after 96 hour these changes diminished. This suggests hemodynamic adaptation to the HUL conditions that possibly occurs also in real space conditions.

Peterson, Amanda↗

Noninvasive assessment of left atrial maximum dP/dt by a combination of transmitral and pulmonary venous flow

OBJECTIVES: The study assessed whether hemodynamic parameters of left atrial (LA) systolic function could be estimated noninvasively using Doppler echocardiography. BACKGROUND: Left atrial systolic function is an important aspect of cardiac function. Doppler echocardiography can measure changes in LA volume, but has not been shown to relate to hemodynamic parameters such as the maximal value of the first derivative of the pressure (LA dP/dt(max)). METHODS: Eighteen patients in sinus rhythm were studied immediately before and after open heart surgery using simultaneous LA pressure measurements and intraoperative transesophageal echocardiography. Left atrial pressure was measured with a micromanometer catheter, and LA dP/dt(max) during atrial contraction was obtained. Transmitral and pulmonary venous flow were recorded by pulsed Doppler echocardiography. Peak velocity, and mean acceleration and deceleration, and the time-velocity integral of each flow during atrial contraction was measured. The initial eight patients served as the study group to derive a multilinear regression equation to estimate LA dP/dt(max) from Doppler parameters, and the latter 10 patients served as the test group to validate the equation. A previously validated numeric model was used to confirm these results. RESULTS: In the study group, LA dP/dt(max) showed a linear relation with LA pressure before atrial contraction (r = 0.80, p < 0.005), confirming the presence of the Frank-Starling mechanism in the LA. Among transmitral flow parameters, mean acceleration showed the strongest correlation with LA dP/dt(max) (r = 0.78, p < 0.001). Among pulmonary venous flow parameters, no single parameter was sufficient to estimate LA dP/dt(max) with an r2 > 0.30. By stepwise and multiple linear regression analysis, LA dP/dt(max) was best described as follows: LA dP/dt(max) = 0.1 M-AC +/- 1.8 P-V - 4.1; r = 0.88, p < 0.0001, where M-AC is the mean acceleration of transmitral flow and P-V is the peak velocity of pulmonary venous flow during atrial contraction. This equation was tested in the latter 10 patients of the test group. Predicted and measured LA dP/dt(max) correlated well (r = 0.90, p < 0.0001). Numerical simulation verified that this relationship held across a wide range of atrial elastance, ventricular relaxation and systolic function, with LA dP/dt(max) predicted by the above equation with r = 0.94. CONCLUSIONS: A combination of transmitral and pulmonary venous flow parameters can provide a hemodynamic assessment of LA systolic function.

NASA Discipline Cardiopulmonary↗

Raised cerebrovascular resistance in idiopathic orthostatic intolerance: evidence for sympathetic vasoconstriction

Patients with idiopathic orthostatic intolerance (IOI) exhibit symptoms suggestive of cerebral hypoperfusion and an excessive decrease in cerebral blood flow associated with standing despite sustained systemic blood pressure. In 9 patients (8 women and 1 man aged 22 to 48 years) with IOI, we tested the hypothesis that volume loading (2000 cc normal saline) and alpha-adrenoreceptor agonism improve systemic hemodynamics and cerebral perfusion and that the decrease in cerebral blood flow with head-up tilt (HUT) could be attenuated by alpha-adrenoreceptor blockade with phentolamine. At 5 minutes of HUT, volume loading (-20+/-3.2 bpm) and phenylephrine (-18+/-3.4 bpm) significantly reduced upright heart rate compared with placebo; the effect was diminished at the end of HUT. Phentolamine substantially increased upright heart rate at 5 minutes (20+/-3.7 bpm) and at the end of HUT (14+/-5 bpm). With placebo, mean cerebral blood flow velocity decreased by 33+/-6% at the end of HUT. This decrease in cerebral blood flow with HUT was attenuated by all 3 interventions. We conclude that in patients with IOI, HUT causes a substantial decrease in cerebrovascular blood flow velocity. The decrease in blood flow velocity with HUT can be attenuated with interventions that improve systemic hemodynamics and therefore decrease reflex sympathetic activation. Moreover, alpha-adrenoreceptor blockade also blunts the decrease in cerebral blood flow with HUT but at the price of deteriorated systemic hemodynamics. These observations may suggest that in patients with IOI, excessive sympathetic activity contributes to the paradoxical decrease in cerebral blood flow with upright posture.

Non-NASA Center↗

High-speed volumetric two-photon fluorescence imaging of neurovascular dynamics

Abstract Understanding the structure and function of vasculature in the brain requires us to monitor distributed hemodynamics at high spatial and temporal resolution in three-dimensional (3D) volumes in vivo. Currently, a volumetric vasculature imaging method with sub-capillary spatial resolution and blood flow-resolving speed is lacking. Here, using two-photon laser scanning microscopy (TPLSM) with an axially extended Bessel focus, we capture volumetric hemodynamics in the awake mouse brain at a spatiotemporal resolution sufficient for measuring capillary size and blood flow. With Bessel TPLSM, the fluorescence signal of a vessel becomes proportional to its size, which enables convenient intensity-based analysis of vessel dilation and constriction dynamics in large volumes. We observe entrainment of vasodilation and vasoconstriction with pupil diameter and measure 3D blood flow at 99 volumes/second. Demonstrating high-throughput monitoring of hemodynamics in the awake brain, we expect Bessel TPLSM to make broad impacts on neurovasculature research.

59 BASIC BIOLOGICAL SCIENCES↗

Feasibility of Vascular Parameter Estimation for Assessing Hypertensive Pregnancy Disorders

Abstract Hypertensive pregnancy disorders (HPDs), such as pre-eclampsia, are leading sources of both maternal and fetal morbidity in pregnancy. Noninvasive imaging, such as ultrasound (US) and magnetic resonance imaging (MRI), is an important tool for predicting and monitoring these high risk pregnancies. While imaging can measure hemodynamic parameters, such as uterine artery pulsatility and resistivity indices (PI and RI), the interpretation of such metrics for disease assessment relies on ad hoc standards, which provide limited insight to the physical mechanisms underlying the emergence of hypertensive pregnancy disorders. To provide meaningful interpretation of measured hemodynamic data in patients, advances in computational fluid dynamics can be brought to bear. In this work, we develop a patient-specific computational framework that combines Bayesian inference with a reduced-order fluid dynamics model to infer parameters, such as vascular resistance, compliance, and vessel cross-sectional area, known to be related to the development of hypertension. The proposed framework enables the prediction of hemodynamic quantities of interest, such as pressure and velocity, directly from sparse and noisy MRI measurements. We illustrate the effectiveness of this approach in two systemic arterial network geometries: an aorta with branching carotid artery and a maternal pelvic arterial network. For both cases, the model can reconstruct the provided measurements and infer parameters of interest. In the case of the maternal pelvic arteries, the model can make a distinction between the pregnancies destined to develop hypertension and those that remain normotensive, expressed through the value range of the predicted absolute pressure.

Biophysics↗

Influence of Blood Rheology and Turbulence Models in the Numerical Simulation of Aneurysms

An aneurysm is a vascular malformation that can be classified according to its location (cerebral, aortic) or shape (saccular, fusiform, and mycotic). Recently, the study of blood flow interaction with aneurysms has gained attention from physicians and engineers. Shear stresses, oscillatory shear index (OSI), gradient oscillatory number (GON), and residence time have been used as variables to describe the hemodynamics as well as the origin and evolution of aneurysms. However, the causes and hemodynamic conditions that promote their growth are still under debate. The present work presents numerical simulations of three types of aneurysms: two aortic and one cerebral. Simulation results showed that the blood rheology is not relevant for aortic aneurysms. However, for the cerebral aneurysm case, blood rheology could play a relevant role in the hemodynamics. The evaluated turbulence models showed equivalent results in both cases. Lastly, a simulation considering the fluid–structure interaction (FSI) showed that this phenomenon is the dominant factor for aneurysm simulation.

59 BASIC BIOLOGICAL SCIENCES↗

Correlation of macro and micro cardiovascular function during weightlessness and simulated weightlessness

The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermo-neutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the performed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.

NASA Discipline Number 00-00↗

Adrenergic responsiveness is reduced, while baseline cardiac function is preserved in old adult conscious monkeys

To examine the physiological deficit to adrenergic stimulation with aging, five younger adult (3 +/- 1 yr old) and nine older adult (17 +/- 1 yr old) healthy monkeys were studied after instrumentation with a left ventricular (LV) pressure gauge, aortic and left atrial catheters, and aortic flow probes to measure cardiac output directly. There were no significant changes in baseline hemodynamics in conscious older monkeys. For example, an index of contractility, the first derivative of LV pressure (LV dP/dt) was similar (3,191 +/- 240, young vs. 3,225 +/- 71 mmHg/s, old) as well as in isovolumic relaxation, tau (24.3 +/- 1.7 ms, young vs. 23.0 +/- 1.0 ms, old) was similar. However, inotropic, lusitropic, and chronotropic responses to isoproterenol (Iso; 0.1 micrograms/kg), norepinephrine (NE; 0.4 micrograms/kg), and forskolin (For; 75 nmol/kg) were significantly (P < 0.05) depressed in older monkeys. For example. Iso increased LV dP/dt by by 146 +/- 14% in younger monkeys and by only 70 +/- 5% in older monkeys. Iso also reduced tau more in younger monkeys (-28 +/- 7%) compared with older monkeys (-13 +/- 3%). Furthermore, peripheral vascular responsiveness to Iso, NE, For, and phenylephrine (PE; 5 micrograms/kg) was significantly (P < 0.05) reduced in older monkeys. For example, phenylephrine (5 micrograms/kg) increased total peripheral resistence by 69 +/- 4% in younger monkeys and by only 45 +/- 3% in older monkeys. Thus in older monkeys without associated cardiovascular disease, baseline hemodynamics are preserved, but adrenergic receptor responsiveness is reduced systemically, not just in the heart.

Non-NASA Center↗

Superiority of compensatory reserve measurement compared with the Shock index for early and accurate detection of reduced central blood volume status

Shock index (SI) equals the ratio of heart rate (HR) to systolic blood pressure (SBP) with clinical evidence that it is more sensitive for trauma patient status assessment and prediction of outcome compared with either HR or SBP alone. We used lower body negative pressure (LBNP) as a human model of central hypovolemia and compensatory reserve measurement (CRM) validated for accurate tracking of reduced central blood volume to test the hypotheses that SI: (1) presents a late signal of central blood volume status; (2) displays poor sensitivity and specificity for predicting the onset of hemodynamic decompensation; and (3) cannot identify individuals at greatest risk for the onset of circulatory shock. We measured HR, SBP, and CRM in 172 human subjects (19–55 years) during progressive LBNP designed to determine tolerance to central hypovolemia as a model of hemorrhage. Subjects were subsequently divided into those with high tolerance (HT) (n = 118) and low tolerance (LT) (n = 54) based on completion of 60 mm Hg LBNP. The time course relationship between SI and CRM was determined and receiver operating characteristic (ROC) area under the curve (AUC) was calculated for sensitivity and specificity of CRM and SI to predict hemodynamic decompensation using clinically defined thresholds of 40% for CRM and 0.9 for SI. The time and level of LBNP required to reach a SI = 0.9 (~60 mm Hg LBNP) was significantly greater (p < 0.001) compared with CRM that reached 40% at ~40 mm Hg LBNP. Shock index did not differ between HT and LT subjects at 45 mm Hg LBNP levels. ROC AUC for CRM was 0.95 (95% CI = 0.94–0.97) compared with 0.91 (0.89–0.94) for SI (p = 0.0002). Despite high sensitivity and specificity, SI delays time to detect reductions in central blood volume with failure to distinguish individuals with varying tolerances to central hypovolemia.

60 APPLIED LIFE SCIENCES↗