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Biomedical subjects

S F Stewart

Publications and source records attributed to S F Stewart.

At least 19 recordsLinked to original sources

Effects of a vascular graft/natural artery compliance mismatch on pulsatile flow.

Attempts have been made to correlate small-diameter vascular graft patency with compliance matching between the graft and the host artery. Without knowledge about the mechanisms of failure by compliance mismatch, however, such correlations remain empirical. We have developed a flow system which mimics the flow in peripheral arteries and techniques to model a compliance mismatch in a straight elastic tube, as might occur with vascular repair. Our goal was to investigate one proposed mechanism of graft failure by compliance mismatch, that of a blood flow disturbance. Flow visualization experiments showed that, under pulsatile flow, a compliance mismatch caused trapping of 40 microns microspheres at the wall near the distal or downstream anastomosis. This suggests that the presence of a microscopic flow separation or stagnant zone in vivo may contribute to the intimal hyperplasia and thrombosis seen in failed grafts.

Acceleration

Inhibition of human neutrophil activation by the allergic mediator release inhibitor, CI-949.

The allergic mediator release inhibitor Cl-949 [5-methoxy-3-(1-methylethoxy)-1-phenyl-N-1H-tetrazol-5-yl-1H -indole-2-carboxamide, L-arginine salt] was evaluated for its effects on human neutrophil functions. Cl-949 (100 microM) inhibited spontaneous migration and chemotaxis toward f-met-leu-phe (FMLP) by 49.1% and 45.8%, respectively. At the same concentration, Cl-949 inhibited the phagocytosis of serum-opsonized zymosan (SOZ) by 39.0%. Cl-949 inhibited leukotriene B4 and thromboxane B2 release in response to SOZ with IC50s of 2.0 microM and 3.3 microM, while inhibiting the response to FMLP with IC50s of 1.7 and 2.0 microM. Cl-949 also inhibited myeloperoxidase release from primary lysosomal granules in response to the following stimuli with the respective IC50s (microM): C5a (40.3); FMLP (34.4): SOZ (21.4); concanavalin A (Con A) 3.9); and calcium ionophore A23187 (91.2). In contrast, Cl-949 inhibited lysozyme release from secondary granules in response to SOZ and Con A with IC50s of 99.3 and 56.1 microM, while inhibiting the response to C5a, FMLP, and A23187 by 41.2%, 52.4%, and 10.0%, respectively, at 100 microM. Cl-949 (100 microM) had no inhibitory effect against lysozyme release in response to L-alpha-1,2 dioctanoylglycerol (DiC8), or phorbol 12-myristate 13-acetate (PMA). Cl-949 inhibited superoxide anion generation stimulated by FMLP and Con A with IC50s of 33.9 and 25.8 microM, while inhibiting the response to C5a, SOZ, and A23187 by 36.6%, 24.8%, and 14.1% and having no effect on the response to DiC8 or PMA at 100 microM. These results demonstrate preferential inhibition of arachidonic acid metabolism and degranulation of primary lysosomal granules by Cl-949 with selectivity for stimuli which promote intracellular calcium mobilization or calcium influx.

Arachidonic Acid

Errors in pressure gradient measurement by continuous wave Doppler ultrasound: type, size and age effects in bioprosthetic aortic valves.

The accuracy of continuous wave Doppler ultrasound in deriving pressure gradients across bioprosthetic heart valves was evaluated in an in vitro pulse duplicator. Simultaneous pressure transducer and Doppler measurements were made in new and explanted aortic bioprosthetic valves of several sizes and four types: Carpentier-Edwards, Ionescu-Shiley, Hancock standard and Hancock modified. The mean and peak gradients calculated by the modified Bernoulli equation from Doppler velocity measurements were always greater than those measured manometrically, despite corrections for location dependence of the manometric gradient (or pressure recovery). The relation between manometric and ultrasonically determined gradient was found to be statistically dependent on the valve type (mean gradient p less than 0.0001; peak gradient p = 0.0003) and size (mean gradient p = 0.0089; peak gradient p = 0.0107). Effects of implantation were observed, but were not shown to be significant. It is concluded that the continuous wave Doppler velocity data overestimated prosthetic valve pressure gradient in all cases, even when pressure recovery was taken into account. Clinicians should be wary of Doppler data when making major diagnostic or therapeutic decisions.

Aortic Valve

Predicting the compliance of small diameter vascular grafts from uniaxial tensile tests.

The compliance hypothesis states that the compliance of vascular grafts should match that of the host artery for optimal patency. Although this has not been proven, the literature shows that much effort has gone into measuring compliance. Uniaxial circumferential tensile tests are simpler than compliance tests, but do not give the compliance (a multiaxial property) directly. Therefore, we have used mechanical models to correlate the two. Simple models suffer from inappropriate simplifying assumptions. In a clinically useful range, a Laplace law model and an incremental elasticity model do not predict the compliance from the rigidity as well as does a model derived from finite elasticity. This latter model has helped locate sources of errors. Variations in graft thickness, diameter, and anisotropy may be responsible for scatter in the experimental correlations between compliance and uniaxial rigidity.

Animals

Solid state line scan cameras for measuring strain in soft tissues and implants.

The line scan camera, or LSC, is an inexpensive and easily applied technique for optical strain measurement of soft biomaterials. The LSC is based on a linear array of photodiodes; in gauging applications, where measurements between dark/light interfaces are important, the digital nature of the array can be exploited. Advantages of the LSC include low cost, high frequency response, applicability to front- or back-lighted samples, insensitivity to stray and nonuniform lighting as well as to accidental overexposure, ease and linearity of calibration, and lack of temperature sensitivity. With the 1024 element arrays used herein, the relative resolution is theoretically limited to 1 part in 1024, or 0.1%; in practice, the relative resolution is somewhat poorer. LSCs have been successfully used in mechanical tests to measure the diameter of arteries and compliant vascular grafts, the longitudinal strain of vascular grafts, and the dynamic diameter of elastic tube models of graft/artery systems in pulsatile flow visualization experiments.

Animals

CI-943, a potential antipsychotic agent. II. Neurochemical effects.

The effects of CI-943 (a novel 8-ethyl-7,8-dihydro-1,3,5-trimethyl-1H-imidazo[1,2-c]pyrazolo[3,4- e]pyrimidine compound exhibiting a favorable antipsychotic profile in animal tests) on neurochemical parameters related to biogenic amine neurons have been studied in rat brain. CI-943 (1-40 mg/kg p.o. and 20 mg/kg i.p.) accelerated the turnover of dopamine (DA) in rat brain as demonstrated by the enhancement of levels of the DA metabolites homovanillic acid, 3,4-dihydroxyphenylacetic acid or 3-methoxytyramine and by the enhancement rate of DA synthesis in either striatum or mesolimbic regions. These increases in DA turnover induced by CI-943 are not due to DA receptor blockade as CI-943, unlike known antipsychotics, did not exhibit affinity for DA receptors either in vitro or in vivo and did not affect rat serum basal prolactin levels. Amfonelic acid enhanced the action of haloperidol in increasing striatal homovanillic acid with no effect on that of CI-943 and clozapine, suggesting that CI-943, like clozapine, would be predicted to have a low risk of extrapyramidal side effects as compared to haloperidol. Chronic administration of CI-943 (40 mg/kg i.p.) to rats for 28 days did not affect the affinity or number of striatal DA receptors; in comparison haloperidol (0.5 mg/kg i.p.) caused an increase in number of DA receptors with no change in affinity. Measures of serotonergic function were increased; noradrenergic function was not affected by CI-943, nor did it exhibit affinity for a number of central nervous system receptors in vitro. The molecular mechanism by which CI-943 increases brain DA turnover is not known at this time but appears to be unique in comparison to known antipsychotic agents.

Animals

Finite elasticity modeling of the biaxial and uniaxial properties of compliant vascular grafts.

Compliant vascular grafts were modeled by finite elasticity theory. A linear, biaxial model satisfactorily described the stress-strain behavior in inflation tests, where the sample length was fixed longitudinally and inflated. The model was then used to predict the behavior in a longitudinal test (where the longitudinal stretch was varied while keeping the pressure zero), and in a uniaxial test of a circumferential strip. The model satisfactorily predicted the longitudinal Young's modulus measured in the longitudinal test. The model was less successful in predicting the circumferential Young's modulus measured in the uniaxial test, possibly because the state of stress was not purely uniaxial.

Blood Vessel Prosthesis

CI-922--a novel, potent antiallergic compound--I. Inhibition of mediator release in vitro.

CI-922 (3,7-dimethoxy-4-phenyl-N-1H-tetrazol-5-yl-4H-furo[3,2-b]-indole- 2-carboxamide, L-arginine salt) is a novel antiallergy compound which inhibits the release of the inflammatory mediators histamine and leukotriene (LT) from stimulated cells. CI-922 showed potent, effective inhibition of antigen-induced mediator release from human basophils and isolated guinea pig lung. The drug inhibited ragweed or housedust-induced histamine release from basophils of allergic human donors (IC50 = 8.6 microM). The antiallergy agents proxicromil (IC50 = 80 microM) and cromolyn (100 microM) were less potent than CI-922 or inactive, respectively. In fragmented lung from actively sensitized guinea pigs, CI-922 (IC50 = 1.5 microM), blocked the antigen-induced production of LT and was a more potent inhibitor of histamine release (IC50 = 13.4 microM) than proxicromil (IC50 = 72.9 microM), or cromolyn (inactive at 1 mM). CI-922 (IC50 = 0.9 microM) completely inhibited repeated contractions of guinea pig lung strips that were induced by low antigen concentration in the presence of antihistamine (H1). Nordihydroguaiaretic acid (NDGA) (IC50 = 2.8 microM), proxicromil (IC50 = 6.2 microM) and the LT antagonist FPL-55712 (IC50 = 3.3 microM) also were fully effective, but cromolyn (300 microM) was inactive. In other experiments, CI-922 (IC50 = 7.0 microM) inhibited a strong, nonrepeatable lung contraction induced with high antigen concentration (histamine responses blocked), and was six times more potent than FPL-55712. Other investigations in isolated tissue preparations showed CI-922 to be a weak inhibitor of LT or histamine-induced effects with no anticholinergic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Increase of rat serum prolactin by adenosine analogs and their blockade by the methylxanthine aminophylline.

The administration of the stable adenosine analogs N6-[(R)-methyl-2-phenylethyl]adenosine (R-PIA; 0.01-1.0 mg/kg i.p.) and 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-D-ribofuronamide (NECA; 0.01-1.0 mg/kg i.p.) caused a dose-related (NECA) or biphasic (R-PIA) increases in rat serum prolactin. The S-isomer of PIA was inactive up to 4 mg/kg i.p. The methylxanthine aminophylline (10 and 30 mg/kg i.p.) antagonized the R-PIA- and NECA-induced elevation of prolactin suggesting an adenosine receptor-mediated effect. The dopaminergic agents L-dopa and bromocriptine antagonized the R-PIA and NECA-induced increase in serum prolactin. Haloperidol (a dopamine antagonist) and alpha-methyl-p-tyrosine (a catecholamine synthesis inhibitor) potentiated the R-PIA-induced effects. R-PIA and NECA did not displace 3H-haloperidol from rat striatal membranes nor effect in vitro prolactin release from rat anterior pituitary cells grown in culture. Based upon these findings it is postulated that R-PIA and NECA may be increasing prolactin secretion in part by inhibiting central dopamine release, although other mechanisms may also be operating.

Adenosine

Wheelchair cushion effect on skin temperature, heat flux, and relative humidity.

For patients subject to decubitus ulcers, wheelchair cushions should be prescribed with knowledge of the cushion's effect on the thermal as well as mechanical environment of the skin. To define thermal effects that may be encountered during routine use, tests werr made on 24 commercially available cushions. Skin temperature, heat flux and relative humidity were measured under the ischial tuberosities of a normal 24-year-old man during a 1-hour period of sitting on each cushion. After 1 hour, skin temperatures increased by means of 3.4 C and 2.8 C on foams and viscoelastic foams and there were slight decreases in heat flux as compared with control values in air. On gels, skin temperatures remained constant and heat flux increased, while water "floatation" pads caused a mean skin temperature decreased of 2.7 C along with a marked increase in heat flux. Relative humidity at the skin cushion interface increased by 10.4%, 22.8% and 19.8% on foams, gels and water floatation pads, as compared with room air values. Representative cushions from each of the general types (foam, viscoelastic foam, gel and water floatation) also were subjected to 2-hour tests which indicated the measured parameters continued to change asymptotically.

Adult

Changes in pituitary hormone secretions and corpora lutea following PGF2alpha administration to PMS/hCG-stimulated rats.

Pseudopregnancy was induced in 26 day old female rats by giving 30 IU of PMS followed 56 hours later with 5 IU of hCG. Day 1 of pseudopregnancy was considered established 72 hours after PMS administration. Pseudopregnancy lasted 14 to 15 days. Ovarian weights increased for 4 to 8 times due to treatment. Histological examiniation of the corpora lutea (CL) of pseudopregnancy suggested luteolysis began on day 6 and extended to day 8. A "new" crop of CL appeared on day 9 suggesting the duration of pseudopregnancy was supported by more than one generation of CL or by CL maturing at different rates. Twice daily administration of 1 mg PGF2alpha on days 5 to 8 prevented the appearance of the "new" CL on day 9, and increased signs of luteolysis in the initially formed CL. Lower doses (0.01 and 0.1 mg, b.i.d., X 4 days) delayed the appearance of "new" CL until day 10. Blood samples withdrawn between 0930 and 1100 hours were analysed for FSH, LH and prolactin. Animals treated with 0.01 and 0.1 mg of PGF2alpha, b.i.d., X 4 days had increased LH values on day 8, thus the PG appeared luteotrophic. Rats treated with 1 mg of PGF2alpha, b.i.d., X 4 days had decreased LH values on day 7 and the CL showed subsequent luteolysis. FSH levels were relatively constant during pseudopregnancy. However, all doses of PGF2alpha reduced FSH levels on day 7. An associated decrease in uterine weight occurred, possibly due to reduced follicular development. Prolactin levels fell in response to PGF2alpha treatment which undoubtedly contributed to the observed luteolysis. The signs of early cessation of pseudopregnancy were: increased serum FSH on days 9 and 10; increasing uterine weight; and the reappearance of follicular growth. These data suggest that PGF2alpha reduced the duration of pseudopregnancy primarily by inhibiting the secretion of FSH, LH and prolactin.

Animals

A comprehensive cardiovascular waveform analysis program for IBM-compatible personal computers.

Computerized cardiovascular waveform processing has become a necessary and fundamental tool in the analysis of physiologic data. The availability of numerous commercial data-analysis programs has significantly enhanced the efficiency of waveform analysis. Many such programs come with their own programming language, which enables the researcher to create an application program suited to a specific series of calculations. Once written, an application program can significantly increase the efficiency with which data from a specific experiment can be analyzed. However, creating or modifying a program for each new experimental protocol can be time-consuming, especially in the error-detection and verification stages. Single-purpose programs also prove somewhat inflexible to unexpected changes in experimental formats. These problems suggested the need for a more flexible program, but one that is nevertheless specifically suited to the analysis of cardiovascular signals. This need led to the development of a program designed in collaboration with surgeons and physiologists. This program addresses some important analysis problems in cardiovascular research, and allows the user to survey and manipulate cardiovascular waveforms in an intuitive and spontaneous manner.

Algorithms

In vitro quantification of regurgitant jet flow by color Doppler ultrasound and conservation of momentum.

Prosthetic valve regurgitant jets can be imaged with color Doppler ultrasound (CDU), but clinical quantitation remains elusive. An equation based on an integrated conservation of momentum analysis was implemented for CDU quantitation of regurgitation. This was compared with a simple, non-CDU momentum balance analysis recently reported that requires only a pulsed Doppler ultrasound (PDU) reading within the jet and a continuous wave Doppler (CWD) reading of the orifice velocity. For in vitro steady flows, the simple, non-CDU method was accurate only with PDU readings taken 5 cm from the orifice; flows were underestimated when readings 1 and 3 cm from the orifice were used. The CDU method was accurate, even when flows calculated from readings between 0.5 and 6.0 cm from the orifice were averaged together.

Blood Flow Velocity

In vitro ultrasound characterization of a polyurethane trileaflet valve.

Polyurethane synthetic trileaflet valves were compared with commercial prostheses in vitro, in a pulse duplicator using ultrasound to characterize the flow velocities and patterns. Flow-pressure drop behavior was in the middle range of other prosthetic valves. Diastolic regurgitant jets were located by color Doppler ultrasound, and there appeared to be some leakage through the leaflet fold at the commissure. Nevertheless, the closing volumes and closed valve leakage volumes were, on average, lower than other prosthetic valves. Systolic 20 Hz spectral oscillations detected with pulsed Doppler and continuous wave Doppler were attributed to leaflet flutter in the open valve.

Aortic Valve