C F Knapp

University of Kentucky, Lexington, Kentucky, United States

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Publications (70)213.99 Total impact

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    ABSTRACT: Purpose: In addition to serious bone, vestibular, and muscle deterioration, space flight leads to cardiovascular dysfunction upon return to gravity. In seeking a countermeasure to space flight-induced orthostatic intolerance, we previ ously determined that exposure to artificial gravity (AG) training in a centrifuge improved orthostatic tolerance of ambulatory subjects. This protocol was more effective in men than women and more effective when subjects exercised. Methods: We now determine the orthostatic tolerance limit (OTL) of cardiovascularly deconditioned (furosemide) men and women on one day following 90 min of AG compared to a control day (90 min of head-down bed rest, HDBR). Results: There were three major findings: a short bout of artificial gravity improved orthostatic tolerance of hypovolemic men (30 %) and women (22 %). Men and women demonstrated different mechanisms of cardiovascular regulation on AG and HDBR days; women maintained systolic blood pressure the same after HDBR and AG exposure while men's systolic pressure dropped (11 ± 2.9 mmHg) after AG. Third, as presyncopal symptoms developed, men's and women's cardiac output and stroke volume dropped to the same level on both days, even though the OTL test lasted significantly longer on the AG day, indicating cardiac filling as a likely variable to trigger presyncope. Conclusions: (1) Even with gender differences, AG should be considered as a space flight countermeasure to be applied to astronauts before reentry into gravity, (2) men and women regulate blood pressure during an orthostatic stress differently following exposure to artificial gravity and (3) the trigger for presyncope may be cardiac filling.
    Full-text · Article · Oct 2015 · Arbeitsphysiologie
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    ABSTRACT: We investigated whether and how cardiovascular and cardiorespiratory phase synchronization would respond to changes in hydration status and orthostatic stress. Four men and six women were tested during graded head-up tilt (HUT) in both euhydration and dehydration (DEH) conditions. Continuous R-R intervals (RRI), systolic blood pressure (SBP) and respiration were investigated in low (LF 0.04-0.15 Hz) and high (HF 0.15-0.4 Hz) frequency ranges using a phase synchronization index (λ) ranging from 0 (complete lack of interaction) to 1 (perfect interaction) and a directionality index (d), where a positive value of d reflects oscillator 1 driving oscillator 2, and a negative value reflects the opposite driving direction. Surrogate data analysis was used to exclude relationships that occurred by chance. In the LF range, respiration was not synchronized with RRI or SBP, whereas RRI and SBP were phase synchronized. In the HF range, phases among all variables were synchronized. DEH reduced λ among all variables in the HF and did not affect λ between RRI and SBP in the LF region. DEH reduced d between RRI and SBP in the LF and did not affect d among all variables in the HF region. Increasing λ and decreasing d between SBP and RRI were observed in the LF range during HUT. Decreasing λ between SBP and RRI, respiration and RRI, and decreasing d between respiration and SBP were observed in the HF range during HUT. These results show that orthostatic stress disassociated interactions among RRI, SBP and respiration, and that DEH exacerbated the disconnection.
    No preview · Article · Oct 2014 · Arbeitsphysiologie
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    ABSTRACT: Purpose: Harmful effects of inhaled particulates have been established in epidemiologic studies of ambient air pollution. In particular, heart rate variability responses to high levels of environmental tobacco smoke (ETS), similar to responses observed during direct smoking, have been reported. We sought to determine whether such responses could be observed at lower particulate concentrations. Methods: We monitored cardiovascular responses of non-smoking 21 women and 19 men to work-place-relevant levels of: ETS, cooking oil fumes (Coil), wood smoke (WS), and water vapor as sham control. Responses, tested on three consecutive days (random order of aerosol presentation), were averaged for each subject. Results: Low frequency spectral powers of heart rate and blood pressure rose during recovery from exposure to particulate, but not to sham exposures. At breathing frequencies, spectral power of men's systolic pressure doubled, and baroreflex effectiveness increased, following ETS exposure. An index of sympathetic control of heart rate was more pronounced in men than women, in response to ETS and Coil, compared to WS and sham. Conclusions: When measured under controlled conditions, autonomic activities in non-smoking men and women exposed to low level, short term, particulate concentrations were similar to those observed during longer term, higher level exposures to ETS and to direct smoking. These increased indexes of sympathetic control of heart rate and peripheral vasomotion followed introduction of particulates by about 15 min. Finally, coupling of heart rate and systolic pressure indicated an increase in baroreflex activity in the response to breathing ETS that was less effective in men than women.
    Full-text · Article · Oct 2014 · Arbeitsphysiologie
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    ABSTRACT: Earth-based simulations of physiologic responses to space mission activities are needed to develop prospective countermeasures. To determine whether upright lower body positive pressure (LBPP) provides a suitable space mission simulation, we investigated the cardiovascular responses of normovolemic and hypovolemic men and women to supine and orthostatic stress induced by head-up tilt (HUT) and upright LBPP, representing standing in lunar, Martian, and Earth gravities. Six men and six women were tested in normovolemic and hypovolemic (furosemide, intravenous, 0.5 mg x kg(-1)) conditions. Continuous electrocardiogram, blood pressure, segmental bioimpedance, and stroke volume (echocardiography) were recorded supine and at lunar, Martian, and Earth gravities (10 degrees, 20 degrees, and 80 degrees HUT vs. 20%, 40%, and 100% bodyweight upright LBPP), respectively. Cardiovascular responses were assessed from mean values, spectral powers, and spontaneous baroreflex parameters. Hypovolemia reduced plasma volume by approximately 10% and stroke volume by approximately 25% at supine, and increasing orthostatic stress resulted in further reductions. Upright LBPP induced more plasma volume losses at simulated lunar and Martian gravities compared with HUT, while both techniques induced comparable central hypovolemia at each stress. Cardiovascular responses to orthostatic stress were comparable between HUT and upright LBPP in both normovolemic and hypovolemic conditions; however, hypovolemic blood pressure was greater during standing at 100% bodyweight compared to 80 degree HUT due to a greater increase of total peripheral resistance. The comparable cardiovascular response to HUT and upright LBPP support the use of upright LBPP as a potential model to simulate activity in lunar and Martian gravities.
    Full-text · Article · Apr 2014 · Aviation Space and Environmental Medicine
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    ABSTRACT: In this study we compare two models [head-up tilt (HUT) vs. body unweighting using lower body positive pressure (LBPP)] to simulate Moon, Mars, and Earth gravities. A literature search did not reveal any comparisons of this type performed previously. We hypothesized that segmental fluid volume shifts (thorax, abdomen, upper and lower leg), cardiac output, and blood pressure (BP), heart rate (HR), and total peripheral resistance to standing would be similar in the LBPP and HUT models. There were 21 subjects who were studied while supine (simulation of spaceflight) and standing at 100% (Earth), 40% (Mars), and 20% (Moon) bodyweight produced by LBPP in Alter-G and while supine and tilted at 80 degrees, 20 degrees, and 10 degrees HUT (analogues of Earth, Mars, and Moon gravities, respectively). Compared to supine, fluid shifts from the chest to the abdomen, increases in HR, and decreases in stroke volume were greater at 100% bodyweight than at reduced weights in response to both LBPP and HUT. Differences between the two models were found for systolic BP, diastolic BP, mean arterial BP, stroke volume, total peripheral resistance, and thorax and abdomen impedances, while HR, cardiac output, and upper and lower leg impedances were similar. Bodyweight unloading via both LBPP and HUT resulted in cardiovascular changes similar to those anticipated in actual reduced gravity environments. The LBPP model/Alter-G has the advantage of providing an environment that allows dynamic activity at reduced bodyweight; however, the significant increase in blood pressures in the Alter-GC may favor the HUT model.
    No preview · Article · Apr 2014 · Aviation Space and Environmental Medicine
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    ABSTRACT: We hypothesized that human cardiovascular responses to standing in reduced gravity environments, as on the Moon or Mars, could be modeled using a lower body positive pressure (LBPP) chamber. Heart rate, blood pressure, body segment fluid shifts, ECG, indexes of sympathetic, parasympathetic balance, and baroreflex control of the heart and periphery plus echocardiographic measures of cardiac function were recorded from seven men and seven women supine and standing at 100% (Earth), 40% (-Mars), and 20% (-Moon) bodyweights (BW). The fluid shifted from the chest was greater when standing at 100% BW than at 20% and 40% BW, while fluid pooled in the abdomen was similar at all BWs. Compared to moving from supine to standing at 100% BW, moving to 20% and 40% BW resulted in smaller decreases in stroke volume and pulse pressure, smaller increases in heart rate and smaller decreases in parasympathetic control of heart rate, baroreflex slope, numbers of blood pressure ramps, and much reduced indexes of sympathetic drive to the heart and periphery. However, peripheral vascular resistance, systolic pressure, and baroreflex effectiveness were elevated during 20% and 40% BW, compared to supine and standing at 100% BW. Standing at reduced bodyweight suppressed indexes of sympathetic control of heart rate and peripheral vasomotion. Regulatory responses indicated a combination of arterial and cardiopulmonary baroreflex control: mean heart rate, vasomotion, and baroreflex sensitivity appeared to be more under cardiopulmonary control while baroreflex effectiveness appeared to be driven more by the arterial baroreflex.
    Full-text · Article · Nov 2013 · Aviation Space and Environmental Medicine
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    ABSTRACT: Cardiac and vascular dysfunctions resulting from autonomic neuropathy (AN) are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure (BP) regulation in patients with peripheral neuropathy and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. We continuously measured electrocardiogram, arterial BP, and respiration during supine rest and 70° head-up tilt in 12 able-bodied subjects, 7 diabetics without, 7 diabetics with possible, and 8 diabetics with definite, sensory, and/or motor neuropathy (D2). During the first 3 min of tilt, systolic BP (SBP) of D2 decreased [-10.9 ± 4.5 (SE) mmHg] but increased in able-bodied (+4.8 ± 5.4 mmHg). Compared with able-bodied, D2 had smaller low-frequency (0.04-0.15 Hz) spectral power of diastolic BP, lower baroreflex effectiveness index (BEI), and more SBP ramps. Except for low-frequency power of SBP, D2 had greater SBP and smaller RR interval harmonic and nonharmonic components at rest across the 0.003- to 0.45-Hz region. In addition, our results support previous findings of smaller HF RR interval power, smaller numbers of baroreflex sequences, and lower baroreflex sensitivity in D2. We conclude that diabetic peripheral neuropathy is accompanied by diminished parasympathetic and sympathetic control of heart rate and peripheral vasomotion and diminished baroreflex regulation. A novel finding of this study lies in the sensitivity of BEI to detect AN, presumably because of its combination of parameters that measure reductions in both sympathetic control of vasomotion and parasympathetic control of heart rate.
    Full-text · Article · Nov 2011 · AJP Regulatory Integrative and Comparative Physiology
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    ABSTRACT: We studied 15 men (8 treatment, 7 control) before and after 21 days of 6º head-down tilt to determine whether daily, 1-h exposures to 1.0 G(z) (at the heart) artificial gravity (AG) would prevent bed rest-induced cardiovascular deconditioning. Testing included echocardiographic analysis of cardiac function, plasma volume (PV), aerobic power (VO(2)pk) and cardiovascular and neuroendocrine responses to 80º head-up tilt (HUT). Data collected during HUT were ECG, stroke volume (SV), blood pressure (BP) and blood for catecholamines and vasoactive hormones. Heart rate (HR), cardiac output (CO), total peripheral resistance, and spectral power of BP and HR were calculated. Bed rest decreased PV, supine and HUT SV, and indices of cardiac function in both groups. Although PV was decreased in control and AG after bed rest, AG attenuated the decrease in orthostatic tolerance [pre- to post-bed rest change; control: -11.8 ± 2.0, AG: -6.0 ± 2.8 min (p = 0.012)] and VO(2)pk [pre- to post-bed rest change; control: -0.39 ± 0.11, AG: -0.17 ± 0.06 L/min (p = 0.041)]. AG prevented increases in pre-tilt levels of plasma renin activity [pre- to post-bed rest change; control: 1.53 ± 0.23, AG: -0.07 ± 0.34 ng/mL/h (p = 0.001)] and angiotensin II [pre- to post-bed rest change; control: 3.00 ± 1.04, AG: -0.63 ± 0.81 pg/mL (p = 0.009)] and increased HUT aldosterone [post-bed rest; control: 107 ± 30 pg/mL, AG: 229 ± 68 pg/mL (p = 0.045)] and norepinephrine [post-bed rest; control: 453 ± 107, AG: 732 ± 131 pg/mL (p = 0.003)]. We conclude that AG can mitigate some aspects of bed rest-induced cardiovascular deconditioning, including orthostatic intolerance and aerobic power. Mechanisms of improvement were not cardiac-mediated, but likely through improved sympathetic responsiveness to orthostatic stress.
    Full-text · Article · May 2011 · Arbeitsphysiologie
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    Full-text · Article · May 2011 · Medicine & Science in Sports & Exercise
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    ABSTRACT: We investigated autonomic control of cardiovascular function in able-bodied (AB), paraplegic (PARA), and tetraplegic (TETRA) subjects in response to head-up tilt following spinal cord injury. We evaluated spectral power of blood pressure (BP), baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), occurrence of systolic blood pressure (SBP) ramps, baroreflex sequences, and cross-correlation of SBP with heart rate (HR) in low (0.04-0.15 Hz)- and high (0.15-0.4 Hz)-frequency regions. During tilt, AB and PARA effectively regulated BP and HR, but TETRA did not. The numbers of SBP ramps and percentages of heartbeats involved in SBP ramps and baroreflex sequences increased in AB, were unchanged in PARA, and declined in TETRA. BRS was lowest in PARA and declined with tilt in all groups. BEI was greatest in AB and declined with tilt in all groups. Low-frequency power of BP and the peak of the SBP/HR cross-correlation magnitude were greatest in AB, increased during tilt in AB, remained unchanged in PARA, and declined in TETRA. The peak cross-correlation magnitude in HF decreased with tilt in all groups. Our data indicate that spinal cord injury results in decreased stimulation of arterial baroreceptors and less engagement of feedback control as demonstrated by lower 1) spectral power of BP, 2) number (and percentages) of SBP ramps and barosequences, 3) cross-correlation magnitude of SBP/HR, 4) BEI, and 5) changes in delay between SBP/HR. Diminished vasomotion and impaired baroreflex regulation may be major contributors to decreased orthostatic tolerance following injury.
    Full-text · Article · Apr 2007 · AJP Regulatory Integrative and Comparative Physiology
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    ABSTRACT: Orthostatic intolerance (OI) continues to be a problem experienced by astronauts upon return from spaceflight. Artificial gravity (AG) training via short radius centrifugation has been suggested as a countermeasure to this OI. The purpose of our research was to determine effects of three weeks of intermittent (+1 to +2.5Gz for 35 min/day) AG exposure on normal, ambulatory men and women. The results of this study indicate that 3 weeks of AG training improved orthostatic tolerance in a group of 14 men and 12 women by an average of 13.6%. This improvement was associated with a decrease in arterial pressure and vascular resistance, and increases in stroke volume and low frequency (0.04–0.15 Hz) arterial pressure and heart rate spectral power. These results suggest that improvement may be attributable to increased venous return possibly as a function of increased stress-induced sympathetic activity and/or vascular sympathetic responsiveness.
    Full-text · Article · Feb 2007 · Acta Astronautica
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    ABSTRACT: The purpose of this study was to test the hypothesis that plasma galanin concentration (pGal) is regularly increased in healthy humans with extensive orthostatic stress. Twenty-six test persons (14 men, 12 women) were brought to an orthostatic end point via a progressive cardiovascular stress (PCS) protocol consisting of 70 degrees head-up tilt plus increasing levels of lower body negative pressure until either hemodynamically defined presyncope or other signs of orthostatic intolerance occurred (nausea, clammy skin, excessive sweating, pallor of the skin). We further tested for possible gender, gravitational, and muscular training influences on plasma pGal responses: PCS was applied before and after 3 wk of daily vertical acceleration exposure training on a Human Powered Centrifuge. Test persons were randomly assigned to active (with bicycle work) or passive (without work) groups (seven men, six women in each group). Resting pGal was 26+/-3 pg/ml in men and 39+/-15 pg/ml in women (not significant); women had higher galanin responses (4.9-fold increase) than men (3.5-fold, P=0.017) to PCS exposure. Overall, PCS increased pGal to 186+/-5 pg/ml (P=0.0003), without significant differences between presyncope vs. orthostatic intolerance, pre- vs. postcentrifuge, or active vs. passive gravitational training. Increases in pGal were poorly related to synchronous elevations in plasma vasopressin. We conclude that galanin is regularly increased in healthy humans under conditions of presyncopal orthostatic stress, the response being independent of gravity training but larger in women than in men.
    Full-text · Article · Apr 2006 · Journal of Applied Physiology

  • No preview · Article · Mar 2006 · ASAIO Journal
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    ABSTRACT: A Systemic-to-Pulmonary artery (SPA) shunt is a connection used to augment pulmonary blood flow in children with congenital heart disease. Current SPA shunts are made from simple synthetic vascular graft, generally made from polytetrafluroethylene (PTFE). Clinical difficulties in maintaining appropriate balance between the systemic and pulmonary circulations using the existing shunts necessitate the need for an implantable adjustable shunt. An important indication for an adjustable shunt is the Norwood procedure for hypoplastic left heart syndrome (HLHS). An adjustable SPA shunt is being developed in order to achieve full range of control of blood flow between the systemic and pulmonary circulation. For optimizing the design of the shunt, it is necessary to determine the forces required to constrict the pressurized shunt. In this study, a relation between the forces needed to cause a desired constriction of the shunt at constant internal pressure is determined using an in-vitro set up. The set up consists of an hydraulic system to pressurize the shunt at constant internal pressure, a force gauge attached to the plunger to determine the forces required to produce constriction, and mounting stands to hold the shunt and force gauge and also to measure the downward displacement of the plunger. Effects of different (constant) internal pressures, different plunger designs, and different diameter shunts on the forces required under different constraining conditions (enclosing the shunt) are investigated. Results from this study will be used to determine the torque needed to drive the screw plunger mechanism to cause the desired constriction.
    No preview · Article · Jan 2005
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    ABSTRACT: Exposure to spaceflight or simulations of microgravity reduce human postflight orthostatic tolerance. Exercise training and volume loading can reduce associated losses of plasma volume and muscle strength, but are not successful in maintaining postflight orthostatic tolerance. A preliminary study (16) indicated that short bouts of artificial gravity (AG) training on a centrifuge could increase orthostatic tolerance in healthy, ambulatory volunteers. We tested the same AG protocol for its tolerance effect on 14 men who underwent a 3-wk exposure to Gz acceleration training on NASA-Ames' (Moffet Field, CA) human-powered centrifuge. Subjects trained supine (head near the center of rotation) and in pairs (one subject rode passively while the other provided power to operate the 1.9-m centrifuge). The acceleration profile consisted of 7 min at 1 Gz before alternating between 1 and 2.5 Gz at 2-min intervals for 28 min. Each subject's presyncopal orthostatic tolerance limit (to a combination of 70 degrees head-up tilt and increasing lower body negative pressure) was determined before and after training. There were no significant differences between training groups, but presyncopal orthostatic tolerance time was improved 17 +/- 10% (p < 0.05) for the combined groups. Mechanisms associated with increased tolerance included: increased cardiac output (p < 0.04), stroke volume (p < 0.01) and low-frequency spectral power of arterial pressure (p < 0.006), and decreased arterial pressure (p < 0.05) and vascular resistance (p < 0.04). Artificial gravity training in this group of men appears to increase orthostatic tolerance through a combination of decreased vascular resistance and enhanced cardiac function.
    No preview · Article · Nov 2004 · Aviation Space and Environmental Medicine
  • Amit Shah · Charles Fischer · Charles F Knapp · Betty F Sisken
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    ABSTRACT: An interactive image processing program was developed to quantify the effects of various biochemical and physical factors on cultured explants of nerve tissue. We used this method to obtain a growth curve of chick embryo dorsal root ganglia (DRG) in media containing various concentrations of nerve growth factor (NGF). In the past, neurite lengths and numbers were measured manually using collages of 35 mm color photographs or made directly under the microscope. Our new program makes it possible to quantify the growth of whole live, unstained DRG's on photograph collages or digital images with respect to center area, neurite area, total explant area, and the number and length of neurites almost exclusive of background artifacts. After comparing the old and new methods, we conclude that our analysis algorithm correlates well with previously accepted protocols for assessing stimulation and inhibition of growth. It rapidly measures several biologically-relevant properties and provides a means to obtain information on six parameters (neurite area, neurite length, neurite number, center area, total area, neurite density) using a single quantitative method. Neurite area in the presence of 10 ng/ml or 20 ng/ml NGF was the most significantly increased parameter as was expected from previous studies since it includes both neurite length and number as well as any crossing fibers.
    No preview · Article · Aug 2004 · Journal of Neuroscience Methods
  • N R Bates · W I Douglas · T Brown · J D Jacob · C F Knapp

    No preview · Article · Mar 2004 · ASAIO Journal
  • N.V. Thuramalla · W.I. Douglas · C.F. Knapp
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    ABSTRACT: Adjustable systemic to pulmonary artery shunt is being developed to maintain appropriate balance between the systemic and pulmonary flows in infants with single ventricle physiology. Regulation of pulmonary blood flow in first-stage palliative surgery (Norwood procedure) is one of the most important factors for the treatment of hypoplastic left heart syndrome. Effect of internal pressure in an unconstrained and constrained shunt on the forces required to cause a desired constriction in the pressurized shunt are investigated using finite element analysis. Preliminary results presented clearly indicate that the forces required to deform a pressurized shunt are considerably higher in the constrained case when compared to the unconstrained case. But the variation in the internal pressure had a negligible effect on the forces required in both the cases.
    No preview · Article · Jan 2004
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    ABSTRACT: Hypoplastic left heart syndrome (HLHS) is a leading cause of cardiac death among newborns, in which the entire left side of the heart is underdeveloped and unable to support the blood circulation. It is the most common type of single ventricle physiology (SVP) and an important need for an adjustable systemic to pulmonary artery (SPA) shunt. In order to achieve full range control of blood flow between the systemic and pulmonary circulation, an adjustable SPA shunt is being developed. SPA shunts are generally made from FDA approved polytetrafluroethylene (PTFE). A screw-plunger mechanism is being used to cause the desired constriction in the pressurized shunt. It is necessary to optimize the design of the plunger, in order to vary the cross-section of the shunt with minimum forces required. An in vitro set up consisting of a hydraulic circuit to have a constant inlet pressure to the shunt throughout the process and a certain post shunt pressure initially, plunger attached to the force gauge mounted on a stand to cause constriction and measure forces, a mounting stand to hold the shunt and its casing, a flow meter and pressure transducers, is used to determine the effect of various plunger tip shapes. It was observed that wider the plunger, lesser is the force required to cause the same reduction in flow. Flow-displacement-force variations for each plunger tip used are also presented. Results from this study will be used to determine the torque required to drive the screw plunger mechanism to cause the desired constriction.
    No preview · Conference Paper · Jan 2004
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    ABSTRACT: Systemic-pulmonary artery (SPA) shunts are connections that exist to augment pulmonary blood flow in neonates born with single ventricle physiology. An appropriate balance between the systemic and pulmonary circulations is crucial to their survival. To achieve this, an adjustable SPA shunt is being developed at our institution that consists of a 4 mm PTFE tube with a screw plunger mechanism to achieve the desired change in flow rate by increasing pulmonary resistance. To determine the effect this mechanism has on flow patterns, two in vitro models were created; an idealized model with an axisymmetric constriction and a model developed from flow phantoms of the actual shunt under various actuations. These models were used to measure the instantaneous velocity and vorticity fields using PIV. Recirculation regions downstream of the constriction were observed for both models. For the idealized model, a separation region persisted for approximately 2-5 diameters downstream with a flow range between 600-850 cc/min, corresponding to in vivo conditions and a Re of approximately 1000-1500. In the realistic test sections, shedding vortices were visible 2.5 diameters downstream on the opposing side of the imposed constriction. The flow field structure and wall skin friction of the two cases under various conditions will be discussed.
    No preview · Article · Oct 2002

Publication Stats

854 Citations
213.99 Total Impact Points

Institutions

  • 1983-2015
    • University of Kentucky
      • Department of Biomedical Engineering
      Lexington, Kentucky, United States
  • 2004
    • University of California, San Diego
      • Department of Medicine
      San Diego, California, United States
  • 1980
    • Lexington Medical Center
      West Columbia, South Carolina, United States