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The monkey vertical vestibuloocular response: a frequency domain study.

We studied the vertical vestibuloocular response (VVOR) in seven cynomolgus monkeys. Eye movements were measured by the search coil method. We tested the monkeys by rotating them about their interaural axis, which was colinear with gravity. Each monkey was tested by using a standard rotational paradigm that consisted of discrete sinusoidal oscillations at three frequencies (0.01, 0.1, and 1.0 Hz) and six peak velocities (5, 10, 30, 60, 100, and 150 degrees/S). The standard rotational paradigm was applied twice for each of two conditions. The first condition (EOD) consisted of rotations with the animal's vision occluded; the second condition (EOL) consisted of rotations during which the animal was allowed to view a well-lighted room. Using various statistics, we tested the linearity of the sinusoidal slow-phase velocity component of the VVOR. The largest nonlinearity found was a skewness of approximately 14% in the waveform of f = 0.01 Hz. We did not find an amplitude asymmetry between slow-phase eye velocity upward (SPVU) and slow-phase eye velocity downward (SPVD) greater than 6% for any oscillation. Nonlinearities present in the VVOR during testing with vision occluded (EOD condition) disappeared with the addition of vision (EOL condition). Intensity function plots [peak slow-phase eye velocity vs. peak rotator (head) velocity] revealed that at f = 0.01, 0.1, and 1.0 Hz over the intensity range from +/-30 degrees/s to +/-150 degrees/s, the VVOR is highly linear. The lowest correlation coefficient associated with linear regressions of the intensity function data at each frequency was 0.99. Analyses of frequency response functions for the bandwidth f = 0.01 to 1.0 Hz, revealed the following: 1) mean amplitude ratio (AR) and phase overlap for four different stimulus intensities (30, 60, 100, and 150 degrees/s); 2) no significant differences (Mann-Whitney U test, P greater than 0.05) between any AR or phase value for mean peak SPVU and mean peak SPVD re appropriately directed head velocity; 3) no significant differences (Mann-Whitney U test, P greater than 0.05) between AR and phase values for animals tested and then retested 1 mo later with five intervening standard rotational paradigms; 4) a large effect of vision in producing a VVOR with near-unity gain and near-perfect phase compensation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Covariate effects on the apparent clearance of tacrolimus in paediatric liver transplant patients undergoing conversion therapy.

OBJECTIVE: To analyse the influence of covariates on the apparent clearance (CL) of tacrolimus in paediatric liver transplant recipients being converted from cyclosporin to tacrolimus. DESIGN: Retrospective modelling study. PATIENTS AND PARTICIPANTS: 18 children, 13 girls and 5 boys, aged 4 months to 16 years (median 9.1 years) who required conversion to tacrolimus because of acute or chronic rejection or cyclosporin toxicity. METHODS: 287 whole-blood tacrolimus concentrations from therapeutic drug monitoring were used to build a nonlinear mixed-effects population model (NONMEM program) for the apparent clearance of tacrolimus. Variables considered were age, total bodyweight (TBW), body surface area (BSA), time after initiation of treatment (T), gender, haematocrit (Hct), albumin (Alb), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (gammaGT), alkaline phosphatase (ALP), bilirubin (BIL), creatinine clearance (CL(CR)) and dosage of concomitant corticosteroids (EST). RESULTS: TBW, T, BIL and ALT were the covariates that displayed a significant influence on CL according to the final regression model: CL (L/h) = 10.4(TBW/70)3/4 x e(-0.00032 T) x e(-0.057 BIL) x (1 - 0.079 ALT). With this model, the estimates of the coefficients of variation were 24.3% and 29.5% for interpatient variability in CL and residual variability, respectively. CONCLUSIONS: The proposed model for tacrolimus CL can be applied for a priori dosage calculations, although the results should be used with caution because of the unexplained variability in the CL. We therefore recommended close monitoring of tacrolimus whole blood concentrations, especially within the first months of treatment. The best use of the model would be its application in dosage adjustment based on therapeutic drug monitoring and the Bayesian approach.

Adolescent↗

Finite element methods of studying mechanical factors in blood flow.

This paper reviews some biomechanical analyses of blood flow in large arteries based on a general computer modeling using the finite element method. We study the following question: What is the role played by the interrelated factors of mechanical stress, flow irregularities, and diffusion through the endothelium on the etiology of atherosclerosis or the aggravation of vascular injury. It presents the computational features of the method and stresses the physiological significance of the results, such as the effect of geometric complexities, material nonlinearities, and non-Newtonian rheology of the blood. The specific mechanical and fluid dynamic factors analyzed are wall shear stress, flow profiles, and pressure variations. After simulating tubes of circular cross section, we apply the analysis to a number of physiological situations of significance, including blood flow in the entrance region, at bifurcations, in the annular region between an inserted catheter of varying diameter and the vessel. A model study of pulsatile flow in a 60 degree bifurcated channel of velocity profiles provided corroborative measurements of these processes with special emphasis on reversed or distributed flow conditions. The corresponding analysis was extended to the situation in which flow separates and reverses in the neighborhood of stagnation points. This required developing the nonlinear expression for the convective velocity change in the medium. A computer algorithm was developed to handle simultaneous effects of pressure and viscous forces on velocity change across the element and applied to the canine prebranch arterial segment. For mean physiological flow conditions, low shear stresses (0-10 dynes/cm2) are predicted near the wall in the diverging plane, higher values (50 dynes/cm2) along the converging sides of the wall. Backflow is predicted along the outer wall, pressure recovery prior to and into the branches, and a peak shear at the divider lip.

Arteriosclerosis↗

Multiple-dose pharmacokinetics of fluvoxamine in children and adolescents.

OBJECTIVE: To determine the pharmacokinetics of fluvoxamine in children and adolescents and to compare pharmacokinetic data from adolescents to adults from a previous study. METHOD: Fluvoxamine was titrated to a target dose of 100 mg b.i.d. in children (6-11 years) and 150 mg b.i.d. in adolescents (12-17 years) with obsessive-compulsive disorder or other disorder requiring fluvoxamine treatment. Serum samples were collected over 12 hours after 12 or more consecutive doses of 25, 50, 100, and 150 mg. RESULTS: Sixteen children (seven females, nine males) and 18 adolescents (nine females, nine males) were included in the pharmacokinetic analyses. Children demonstrated higher mean peak plasma concentration, higher mean area under the plasma concentration-time curve, and lower apparent oral clearance compared with adolescents. Compared with male children, female children had higher mean area under the plasma concentration-time curve, higher mean peak plasma concentration, and more reports of adverse events. However, the area under the plasma concentration-time curve was not directly correlated with frequency or severity of adverse events. Pharmacokinetics were nonlinear over the dose range studied. No pharmacokinetic differences were apparent between adolescents and adults on 150 mg b.i.d. CONCLUSIONS: These pharmacokinetic results suggest that children (especially females) have a higher exposure to fluvoxamine than adolescents, whereas adolescents and adults appear to have similar exposure to fluvoxamine.

Adolescent↗

An economic analysis of "demand" for food in baboons.

Responding of 6 adult male baboons (Papio c. anubis) was maintained under a fixed-ratio schedule of food reinforcement during daily 22-hr experimental sessions. Completion of the ratio requirement resulted in the delivery of a single 1-g food pellet; supplemental feeding was limited to a daily fruit ration. Ratio values were increased on Mondays, Wednesdays, and Fridays according to the following schedule: 2, 4, 8, 16, 32, 64, 96, 128. Responding under each ratio value was examined four times. Under the Fixed-Ratio 2 conditions, food intake ranged between 300 and 600 g. Ratios were increased for each baboon until food intake decreased to about 100 g (20% to 30% of Fixed-Ratio 2 intake). Increasing the response cost increased total time responding and total daily responding in all baboons, but this increase in responding was not sufficient to maintain stable food intake. Baboons responded between 90 and 180 min per day. The highest running response rates were observed under the Fixed-Ratio 2 and Fixed-Ratio 4 schedules. Running rate was similar across the larger ratio values (greater than Fixed-Ratio 8) but was lower than that observed under the Fixed-Ratio 2 and Fixed-Ratio 4 schedules. Similar results were observed the four times that each fixed-ratio value was tested. Intake as a function of cost was analyzed by fitting data to the nonlinear equation proposed by Hursh, Raslear, Shurtleff, Bauman, and Simmons (1988) for "demand" functions. Demand for food was inelastic over most of the ratio values until food intake decreased to 15% to 55% of baseline. The results indicate that demand functions are appropriate for the study of food intake in baboons, but also caution that intake at the cost when demand shifts from inelastic to elastic and its relationship to maximal intake should also be included in analyses of demand for a commodity.

Animals↗

Buffer effects and threshold effects: an alternative interpretation of nonlinearities in the relationship between social support, stress, and depression.

The common interpretation of statistical interactions of global measures of social support and stress in their effects on depression (the "buffer effect" of social support) as reflecting interactive processes within individuals was examined. It was argued that its adequacy depends on incorrect assumptions about the distribution of depressive symptoms within individuals over time and/or different levels of psychosocial adversity. With hypothetical data sets generated under the assumption of a threshold effect in the development of depression and of additive, rather than interactive, effects of social support and stress, it was demonstrated that spurious "buffer effects" of social support can appear in analyses of cross-sectional data. Methodological and substantive implications are discussed, and strategies for study design and data analysis are proposed that allow to assess whether empirical deviations from linearity are more adequately interpreted as a buffer or as a threshold effect.

Adjustment Disorders↗

Segmentation of endpoint trajectories does not imply segmented control.

While it is generally assumed that complex movements consist of a sequence of simpler units, the quest to define these units of action, or movement primitives, remains an open question. In this context, two hypotheses of movement segmentation of endpoint trajectories in three-dimensional human drawing movements are reexamined: (1) the stroke-based segmentation hypothesis based on the results that the proportionality coefficient of the two-thirds power law changes discontinuously with each new "stroke," and (2) the segmentation hypothesis inferred from the observation of piecewise planar endpoint trajectories of three-dimensional drawing movements. In two experiments human subjects performed a set of elliptical and figure eight patterns of different sizes and orientations using their whole arm in three dimensions. The kinematic characteristics of the endpoint trajectories and the seven joint angles of the arm were analyzed. While the endpoint trajectories produced similar segmentation features to those reported in the literature, analyses of the joint angles show no obvious segmentation but rather continuous oscillatory patterns. By approximating the joint angle data of human subjects with sinusoidal trajectories, and by implementing this model on a 7-degree-of-freedom (DOF) anthropomorphic robot arm, it is shown that such a continuous movement strategy can produce exactly the same features as observed by the above segmentation hypotheses. The origin of this apparent segmentation of endpoint trajectories is traced back to the nonlinear transformations of the forward kinematics of human arms. The presented results demonstrate that principles of discrete movement generation may not be reconciled with those of rhythmic movement as easily as has been previously suggested, while the generalization of nonlinear pattern generators to arm movements can offer an interesting alternative to approach the question of units of action.

Adult↗

Flat medial-lateral conformity in total knee replacements does not minimize contact stresses.

The potential for wear in UHMWPE components for total knee replacements can be reduced by decreasing the stresses and strains arising from tibial-femoral contact. The conformity of the articular surfaces has a large effect on the resultant stresses, and components that achieve flat medial-lateral contact have been assumed to produce the lowest stresses due to their perfect conformity. We computed the stresses arising from curved and flat contact on a half-space using two-dimensional, plane strain elasticity solutions and finite element analyses to compare the performance of curved and flat indenters. These indenters were represented by a polynomial so the profiles could be continuously varied from curved to flat. Curved contact resulted in maximum stresses at the center of contact, while flat contact produced maximum stresses at the edge of contact. In addition, three contemporary tibial configurations (flat-on-flat, curved-on-flat, and curved-on-curved geometries) were analyzed using the finite element method with nonlinear material properties. The maximum contact stress, von Mises stress, and von Mises strain were lowest for the curved-on-curved model. The other configurations resulted in higher contact stresses, von Mises stresses, and von Mises strains. The perfect conformity arising from flat contact did not reduce the contact stresses in the UHMWPE component. The tensile stresses, however, were lowest for the flat-on-flat geometry compared with the other two configurations. Relating these distinct differences could prove useful in interpretation of data from simulator and retrieval studies.

Finite Element Analysis↗

Modeling of time-dependent force response of fingertip to dynamic loading.

An extended exposure to repeated loading on fingertip has been associated to many vascular, sensorineural, and musculoskeletal disorders in the fingers, such as carpal tunnel syndrome, hand-arm vibration syndrome, and flexor tenosynovitis. A better understanding of the pathomechanics of these sensorineural and vascular diseases in fingers requires a formulation of a biomechanical model of the fingertips and analyses to predict the mechanical responses of the soft tissues to dynamic loading. In the present study, a model based on finite element techniques has been developed to simulate the mechanical responses of the fingertips to dynamic loading. The proposed model is two-dimensional and incorporates the essential anatomical structures of a finger: skin, subcutaneous tissue, bone, and nail. The skin tissue is assumed to be hyperelastic and viscoelastic. The subcutaneous tissue was considered to be a nonlinear, biphasic material composed of a hyperelastic solid and an invicid fluid, while its hydraulic permeability was considered to be deformation dependent. Two series of numerical tests were performed using the proposed finger tip model to: (a) simulate the responses of the fingertip to repeated loading, where the contact plate was assumed to be fixed, and the bone within the fingertip was subjected to a prescribed sinusoidal displacement in vertical direction; (b) simulate the force response of the fingertip in a single keystroke, where the keyboard was composed of a hard plastic keycap, a rigid support block, and a nonlinear spring. The time-dependent behavior of the fingertip under dynamic loading was derived. The model predictions of the time-histories of force response of the fingertip and the phenomenon of fingertip separation from the contacting plate during cyclic loading agree well with the reported experimental observations.

Bone and Bones↗

Determination of protonation sites in thermospermine and in some other polyamines by 15N and 13C nuclear magnetic resonance spectroscopy.

The pK values of thermospermine, a novel asymmetric tetraamine (4,8-diazadodecane-1,12-diamine), have been determined for the first time by the conventional titration method with subsequent data analyses. It was found to be the most basic polyamine among naturally occurring tetraamines. The 15N NMR titration method was applied to determine its protonation site. Natural-abundance 15N magnetic resonance spectra of the polyamine have been recorded as a function of pH from its free to the protonated form. Its apparent pK values, as well as the intrinsic chemical shifts for each stage of protonation, have been calculated from the NMR titration curve by using a nonlinear least-squares method. The four protonation sites of thermospermine have been successfully determined to be N12, N1, N-8, and N-4 in that order from the free to the completely protonated form. In a similar manner the protonation sites of spermidine and two symmetric tetraamines, thermine and spermine, have been established. 13C NMR experiments for the four polyamines were almost consistent with those of 15N NMR. Owing to the much higher concentration of the polyamines furnished for NMR titration experiments, the pK values obtained by NMR were larger than those derived by the conventional titration methods.

Binding Sites↗

A suite of Mathematica notebooks for the analysis of protein main chain 15N NMR relaxation data.

A suite of Mathematica notebooks has been designed to ease the analysis of protein main chain 15N NMR relaxation data collected at a single magnetic field strength. Individual notebooks were developed to perform the following tasks: nonlinear fitting of 15N-T1 and -T2 relaxation decays to a two parameter exponential decay, calculation of the principal components of the inertia tensor from protein structural coordinates, nonlinear optimization of the principal components and orientation of the axially symmetric rotational diffusion tensor, model-free analysis of 15N-T1, -T2, and {1H}-15N NOE data, and reduced spectral density analysis of the relaxation data. The principle features of the notebooks include use of a minimal number of input files, integrated notebook data management, ease of use, cross-platform compatibility, automatic visualization of results and generation of high-quality graphics, and output of analyses in text format.

Anisotropy↗

Elastic responses to longitudinal torsion of single-strand, rectangular, orthodontic archwire segments.

OBJECTIVES: This study was undertaken to characterize elastic responses of orthodontic archwire segments in longitudinal torsion, to compare experimental results with predictions from structural engineering theory, and to examine the potential interaction between flexural and torsional responses of archwires. METHODS: Passively straight and deflected rectangular wire segments were activated in torsion to states beyond their elastic limits. The wire parameters that were controlled included: the alloy, the cross-sectional size, and the gauge length. The research design included 48 cells and 240 separate tests. From torque-twist plots, values of elastic stiffness, elastic range, and unit elastic range were obtained. Raw experimental data were subjected to analyses of variance and means to a Tukey's post-hoc test. Mean stiffness and elastic range outcomes were compared with theoretical values. RESULTS: Most plots were generally characteristic of Hookean materials. All three wire parameters significantly influenced the three dependent variables; few statistical interactions emerged. Theoretical stiffness values were reasonably comparable to those obtained experimentally; however, the elastic range predictions were conservative. Torsion theory predicts unit elastic ranges independent of gauge length; the experimental data displayed a nonlinear relationship. The minor influences of flexural deformations on the responses of wire segments activated in torsion are suggested as clinically inconsequential. SIGNIFICANCE: Few clinically relevant, controlled studies of archwire torsion have been published. A modified or new formula is needed to predict elastic range magnitudes of archwires in torsion. When flexure and torsion exist in an archwire, it may be possible to separate them to determine overall structural response.

Alloys↗

Adiposity in adolescents: change in actual BMI works better than change in BMI z score for longitudinal studies.

PURPOSE: Longitudinal epidemiologic studies often relate adiposity changes to suspected causal factors. In growing adolescents, this becomes complicated. Many investigators use within-child change in body mass index (BMI) z scores (Delta z) from sex- and age-specific BMI charts developed by the Centers for Disease Control and Prevention (CDC). These charts, derived from cross-sectional data, may not represent BMI growth patterns of real children. Furthermore, because cross-sectional BMIs are not Gaussian, these z scores are from month-specific transformed distributions, with possible unintended consequences when used longitudinally. Alternatively, we can directly analyze BMI change (Delta BMI). We compare these two widely used measures of change in adiposity. METHODS AND RESULTS: With real adolescent data, we show that annual Delta BMIs have nonlinear peaks that are inconsistent with the CDC curves. We also show that a specified Delta z represents a broad range of adiposity changes for children measured at the same two ages. To see how this affects power, we performed simulation studies confirming that analyzing Delta BMIs in models with hypothesized factors is more powerful than analyzing Delta zs. CONCLUSIONS: In longitudinal studies of adolescent adiposity, investigators should be encouraged to analyze Delta BMI rather than Delta z because analyses using BMI are more powerful and findings presented in BMI units are more interpretable.

Adipose Tissue↗

Evaluation of the methods for first flush analysis in urban watersheds.

The general tendency between the ratio of cumulative pollutant loads and the ratio of cumulative runoff appears as a nonlinear form which can be expressed in the form of a third polynomial. In this paper third degree polynomials were applied to represent the first flush curves based on the relationship between the cumulative pollutant load ratio and cumulative runoff ratio. The quantity of stormwater runoff and quality constituents, including chemical oxygen demand (COD), suspended solids (SS), total Kjeldahl nitrogen (TKN), ortho-phosphorus (PO4-P), total phosphorus (TP), n-hexane extracts (HEM), and iron (Fe) were analysed. The objectives of this study were (1) to characterize the quality of stormwater runoff (2) in order to analyse the cumulative curve area ratio and to calculate the first flush coefficients, (3) while also representing the first flush with a third polynomial equation.

Environmental Monitoring↗

Identification and mapping of human saphenous vein medial smooth muscle proteins by two-dimensional polyacrylamide gel electrophoresis.

Changing smooth muscle phenotype and abnormal cell proliferation are important features of vascular pathology, including the failure of saphenous vein bypass grafts. We have characterised and mapped protein expression in human saphenous vein medial smooth muscle, using two-dimensional (2-D) polyacrylamide gel electrophoresis. The 2-D system comprised a nonlinear immobilised pH 3-10 gradient in the first dimension (separating proteins with isoelectric point values between pH 3-10), and 12%T total gel concentration sodium dodecyl sulphate polyacrylamide gel electrophoresis in the second dimension (separating proteins in the range 14,000-200,000 Daltons). Using a combination of peptide mass fingerprinting by matrix-assisted laser desorption/ionisation-time of flight mass spectrometry and partial amino acid sequencing by nanospray tandem mass spectrometry, a subset of 149 protein spots was analysed, with 129 protein spots being identified and mapped. The data presented here are an important addition to the limited knowledge of venous medial smooth muscle protein expression in vivo. Our protein map will facilitate the identification of proteins differentially expressed in human saphenous vein bypass grafts. In turn, this may lead to the elucidation of molecular events involved in saphenous vein bypass graft failure. The map should also provide a basis for comparative studies of protein expression in vascular smooth muscle of varying origins.

Electrophoresis, Gel, Two-Dimensional↗

Pain measurement scales: a comparison of the visual analogue and faces rating scales in measuring pressure ulcer pain.

OBJECTIVE: Although different pain scales often have been used interchangeably, it is not known whether interchanging them is appropriate. The purpose of this report was twofold: to better understand the statistical properties of the Faces Rating Scale (FRS) so it can be used appropriately in clinical settings and to describe the mathematical relationship between the Visual Analogue Scale (VAS) and the FRS when they are used to quantify pressure ulcer pain in hospitalized elderly patients. DESIGN: Secondary data analyses were performed as part of a cross-sectional study. SETTING AND SUBJECTS: A quality assurance program was undertaken to evaluate pressure ulcer pain perceived by elderly hospitalized patients. All patients without aphasia participated. INSTRUMENTS: The VAS used was a 0 to 100 mm horizontal line demonstrated to have ratio scale properties with high validity and reproducibility, and the FRS used was 6 faces ordered horizontally from smiling to crying, labeled 0 to 5 beneath each face, respectively. METHODS: Nonlinear least squares regression with a Gauss-Newton iterative procedure was used. RESULTS: Among models with cubic, quadratic, and linear terms, only the quadratic term was significant (P <.05). With use of the equation derived, VAS = 3.33*(FRS)(2), the resulting reliability coefficient was r = 0.92. CONCLUSIONS: The nonlinear relationship indicated high reliability between VAS and FRS for pain assessment in populations with diminished verbal and abstract thinking abilities. For readers who would like to translate results from one scale to another, a quadratic equation is provided.

Adult↗

Heart rate variability in young patients with diabetes mellitus and healthy subjects explored by Poincaré and sequence plots.

Autonomic neuropathy is a common complication of the diabetes mellitus (DM). The significance of its early diagnosis is very high because the mortality of the patients with this complication is elevated. Considering the effort to apply new mathematical methods to cardiac dysregulation diagnosis, the major aim of the study was to ascertain which of the new heart rate variability (HRV) parameters are different in young patients with DM type 1 compared with control group. The next aim was to assess the HRV changes during prolonged (40 min) supine rest. The heart rate was continuously recorded during supine rest in 17 young patients with DM type 1 (10 women, 7 men) aged 22.4 +/- 1.0 years (mean +/- SEM). The control group consisted of 17 healthy matched probands. The HRV (time/frequency domains, Poincare and sequence plots, sample entropy) was analysed in two intervals - T1 starting at fifth minute and T2 starting at 30th minute of supine rest. The major results of our study are: the reduced Poincare plot pattern measures in the young DM group; the lower percentage of points in the third quadrant of sequence plot (this parameter was not correlated with the mean heart rate) and significant changes in HRV during supine rest in DM group (in contrast to control subjects). In conclusion, HRV parameters based on nonlinear dynamics were able to distinguish cardiac dysregulation in young patients with DM from the control group. The percentage of points in the third quadrant of sequence plot provides information that is not dependent on mean heart rate. Poincare and sequence plots, together with the rate of HRV changes during supine rest, can provide clinically relevant information usable in diagnosis of the cardiac dysregulation.

Adolescent↗

Left ventricular volume measurement by conductance catheter in intact dogs. Parallel conductance volume depends on left ventricular size.

The conductance catheter is a promising new instrument for continuously measuring left ventricular (LV) volume. Absolute LV volume (V[t]) is related to uncorrected conductance volume, B(t), according to the equation: V(t) = (1/alpha)(B(t) - alpha Vc). The alpha Vc factor represents parallel-conductance volume due to conducting material outside the LV blood pool, and may be estimated by transiently changing blood conductivity using a bolus injection of hypertonic saline. alpha is the slope in the relation between B(t) and true LV volume. We tested the assumption that alpha Vc and alpha are constant over a range of hemodynamic conditions. We performed multiple hypertonic saline alpha Vc determinations in seven intact dogs during control conditions and subsequent temporary balloon occlusions of inferior vena cava (IVCO), aorta (AO), and pulmonary artery (PAO). We also compared B(t) with simultaneous biplane angiographic LV volume during similar control and intervention conditions. The saline-derived alpha Vc was 76 +/- 2 ml during control and fell significantly by -7 +/- 2 ml during IVCO (p less than 0.001) but not during AO or PAO. According to multiple linear regression analyses, the strongest predictor of saline-derived alpha Vc was uncorrected end-systolic Bes, with a sensitivity coefficient of 0.60 +/- 0.06 ml/ml (p less than 0.001). Angiographically derived alpha Vc showed a similar dependence on Bes, with a coefficient of 0.77 +/- 0.14 ml/ml (p less than 0.001). Angiographically determined alpha also showed significant variation with hemodynamic interventions, largely reflecting an underlying dependence on alpha Vc. The variation in alpha Vc and alpha with LV size may stem from nonlinearity in the B(t)-V(t) relation. Although the conductance catheter provides a useful measure of relative LV volume, measurement of absolute LV volume over a wide hemodynamic range using constant alpha Vc and alpha factors is unrealistic. This result calls into question the current use of this technique for the measurement of the absolute end-systolic--pressure-volume relation.

Animals↗