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Biomedical subjects

S L Lehman

Publications and source records attributed to S L Lehman.

18 recordsLinked to original sources
PubMed1997

Calcium removal kinetics of the sarcoplasmic reticulum ATPase in skeletal muscle.

The models of the sarcoplasmic reticulum (SR) Ca pump used to simulate Ca kinetics in muscle fibers are simple but inconsistent with data on Ca binding or steady-state uptake. We develop a model of the SR pump that is consistent with data on transient and steady-state Ca removal and has rate constants identified under near-physiological conditions. We also develop models of the other main Ca-binding proteins in skeletal muscle: troponin C and parvalbumin. These models are used to simulate Ca transients in cut fibers during and after depolarizing pulses. Simulations using the full SR pump model are contrasted with simulations using a Michaelis-Menten (MM) approximation to SR pump kinetics. The MM pump underestimates the amount of Ca released during depolarization, underestimates the initial rate of Ca binding by the pump, and overestimates the later rate of Ca pumping. These errors are due to fast initial binding by the SR pump, which is neglected in the MM approximation.

Adenosine Triphosphatases↗
PubMed1996

Two mathematical models explain the variation in cystometrograms of obstructed urinary bladders.

Overdistension of the urinary bladder, secondary to outlet obstruction, causes cellular changes in the bladder wall, including hypertrophy of the smooth muscle cells, which increase bladder mass. To investigate the effects of increased mass on the cystometrogram (CMG), we have developed two mathematical models. In the first model, we assume that mass is added such that the largest bladder volume at zero transmural pressure, the zero pressure volume (ZPV), is constant, It predicts increased pressures and decreased compliance in the CMG. In the second model, we assume that both mass and ZPV increase proportionally. It predicts unchanged pressures, increased compliance, and increased capacity in the CMG. These results allow use to divide animal experiments in the literature into two groups. Cystometrograms performed on animals that have had outlet obstruction induced by a cuff method, inducing a small increase in mass, belong to the first group: hypertrophy with no change in ZPV. Cystometrograms performed on animals that have had outlet obstruction induced by a ligature method, inducing a large increase in mass, belong to the second group: hypertrophy with increased ZPV. We conclude that increased ZPV results from a more severe obstruction which is indicated by the increased capacity and compliance.

Animals↗
PubMed1995

The effect of urinary bladder shape on its mechanics during filling.

Despite the normal variation in the shape of the urinary bladder, it has always been modeled as a sphere. We have investigated whether its steady-state pressure-volume relation would be significantly different if it were a spheroid. From pressure-volume curves of anesthetized dogs, we deduced stress-strain constitutive relationships for the bladder wall material. We then solved the equilibrium equations for prolate and oblate spheroids with these constitutive relationships and predicted stress, strain, and volume at 120 different transmural pressures and eight different eccentricities of both types of spheroids. The pressure-volume relation of the prolate spheroid never differed very much from that of a sphere. However, an oblate spheroid made of urinary bladder material is significantly more compliant than either a prolate spheroid or a sphere made of the same material. Applications include identification of the position of highest stress in the bladder wall, estimation of material properties of urinary bladders, and determination of the physiological signal indicating bladder fullness.

Algorithms↗
PubMed1993

Does it matter, the shape of the bladder?

To determine if the pressure-volume curve of the urinary bladder is dependent on its shape, we compared the pressure-volume curves of spherical, prolate spheroidal, and oblate spheroidal bladders, all made of the same material. We found that oblate spheroidal bladders are significantly more compliant than either spherical or prolate spheroidal bladders. Since the capacity of normal oblate spheroidal bladders is not larger in vivo than those of any other shape bladder, we have concluded that bladder fullness can not be determined by transmural bladder pressure alone.

Animals↗
PubMed1992

Dantrolene sodium and fatigue of long duration.

A long-lasting impairment of muscular force generation follows fatiguing exercise (fatigue of long duration), the physiological basis of which is not well understood. To investigate the role of reduced calcium release in long-lasting fatigue, we examined the effects of dantrolene sodium, which selectively decreases calcium release from the sarcoplasmic reticulum. The drug impaired muscle function in a pattern identical to that of long-lasting fatigue. The results are consistent with either independent effects of dantrolene and exercise at the same site in the excitation-contraction coupling chain, or independent actions at separate serial sites.

Adult↗
PubMed1992

Human control of a simple two-hand grasp.

We investigated how people control fast, accurate movements of a load using a simple two-hand grasp. By providing a clear instruction to several subjects, we isolated a single control strategy. The kinematics produced by this control strategy are nearly indistinguishable from those produced during singlehand movements, but the torques are quite different: one hand accelerates not only itself, but also the load and the other hand, while the other hand brakes the hand-load-hand system. As a result, the hands squeeze the load with a large force during the movement. The dynamics of the hand-load-hand system are of the same form as the dynamics of a single-hand system. Apparently, by taking advantage of this dynamic similarity and of the spring-like properties of muscle, the human motor control system can control the two-hand grasp system simply by modifying the muscle activation patterns used to control single-hand movements. The task dynamics of two-hand grasp do not require that the load be squeezed during the movement, and squeezing the load wastes torque that could be used to move more quickly. However, the human motor control system may choose this squeezing strategy because it reliably brakes the hand-load-hand system despite inherent variability in the braking of individual hands.

Acceleration↗
PubMed1992

Feedforward stabilization in a bimanual unloading task.

When one hand removes a load from the other hand, feedforward motor commands stabilize the position of the unloaded hand. We studied the stabilization of the postural hand using a novel apparatus that allowed unloading at different rates, and unexpected uncoupling of the unloading force from the postural hand. Feedforward stabilization of hand position was observed in all subjects. This stabilization was achieved both by deactivation of postural agonist muscles and by activation of postural antagonist muscles. The neural feedforward command apparently increased with unloading rate. However, the command only partially canceled the interaction torque generated by removing the load, and stabilization became less effective as unloading rate increased.

Electromyography↗
PubMed1992

Erector spinae activation and movement dynamics about the lumbar spine in lordotic and kyphotic squat-lifting.

Activation of the erector spinae during squat lifts depends on the initial posture of the lumbar spine. The authors assessed erector spinae activation by electromyography during squat lifts from lordotic and kyphotic postures, measured kinematics of the lifts from digitized video images, and inferred torques from the kinematics, using a two-dimensional model of a human lifting in the sagittal plane, with a joint at L3. Lifts from the lordotic initial posture had peak electromyographic signals early in the lift, whereas lifts from kyphotic initial posture had an initial "flexor relaxation," and peak activity in the middle of the lift. Lumbar flexion was much greater in lifts from kyphotic initial position. Torques required about L3 were similar between the two postures, though somewhat larger initially in lifts from kyphosis. The largest torques were therefore sustained by flexed lumbar spines, during periods of little or no erector spinae activity, in lifts made from kyphotic initial position. A sizable portion of the early torque is inertial, and therefore strongly dependent on movement time. Movements with a 30-lb load in the hands were similar, in kinematics and electromyography, to unloaded lifts, though longer in duration. The clinical implications of the differences in activation with posture, the practical implications of the inertial component of torque, and the need for consideration of lumbar posture in future modeling of squat lifting are discussed.

Adult↗
PubMed1992

Adaptation to fatigue of long duration in human wrist movements.

Subjects made fast, accurate, consistent wrist flexions under normal conditions and under conditions of low-frequency fatigue. Movements made 1 h after fatiguing exercise were indistinguishable from those made before exercise, even though twitch tensions were only approximately 60% of their fresh values. Electromyograms (EMGs) recorded from the fatigued muscles were, however, different from those recorded before exercise. EMGs during unfatigued movements showed multiple bursts typical for rapid movements. In the presence of low-frequency fatigue, the duration of the first burst was longer than that under normal conditions, and its onset occurred earlier relative to the initiation of movement. The area of the second agonist burst and, in some cases, the antagonist burst, was increased, although changes in their timings were unclear. We conclude that subjects adapted to low-frequency fatigue by changing the neural patterns controlling their muscles and present a simple model of excitation-contraction coupling that demonstrates how the observed changes in excitation can produce the same kinematics.

Adaptation, Physiological↗
PubMed1991

Measurement of lactate production by tracer techniques.

Tracer methodology is developed for use in the study of lactate metabolism. A one-compartment model introduces the inference of lactate flux from specific activity. Two compartments distinguish between blood and tissue, and give an estimate of tissue specific activity from measurements in blood. The two-compartment model is applied directly to the problem of flux between lactate and pyruvate in a single tissue. It is shown that equilibration between lactate and pyruvate pools does not invalidate the use of tracer methodology to study lactate metabolism. Application of the two-compartment model to a perfused muscle preparation shows that both lactate and pyruvate fluxes can be measured by using tracer techniques. A three-compartment formalism is presented to resolve the controversy regarding sampling and infusion sites, with special attention given to anatomical identity of the sites. Future directions include measurement of tracer transients during tracee steady state, measurement of distribution of blood flow, and further study of isolated organ preparations.

Humans↗
PubMed1990

An identified model for human wrist movements.

We have performed tests to find the mechanical properties of the hand and muscles driving wrist flexion and extension, and have identified parameters of a model. The hand acts as a nearly pure inertial load over most of its range of motion. It can be approximated as a rigid body rotating about a single axis. Viscosity of the wrist joint is negligible. Passive elastic torques are also small, except at extreme wrist angles. We measured torque as a function of wrist angle for maximum voluntary contractions, and angular velocity as a function of load. The torque/velocity curves for shortening muscles are well approximated by a Hill equation. To measure the "series elasticity" of the muscle equivalents, we imposed step changes in torque. The series stiffness is a monotonically increasing function of the preload, or "active state", in the Hill sense. We discuss the relationship of the measured parameters to properties of isolated muscles. To see the implications of the model structure for the "inverse problem" of identifying motor control signals, we simulated four models of different complexities, and found best fits to movement data, assuming simple pulse-shaped inputs. Inferred inputs depend strongly on model complexity. Finally, we compared the best fit control signals to recorded electromyograms.

Adult↗
PubMed1990

Obtaining a representative blood sample in lactate tracer studies.

Reasons why venous tracer infusion with arterial sampling [(v-a) mode] has advantages compared to arterial infusion and venous sampling [(a-v) mode] for studies of blood lactate kinetics are presented. Arterial tracer infusion can result in biased tracer input due to streaming and unequal blood flow distribution. The procedure is impractical for human studies. Venous sampling from the jugular, or any other peripheral or great vein, provides a sample which may, or may not represent mixed venous systemic blood, which exists only in the pulmonary artery. Venous sampling will not represent cardiac lactate metabolism because the coronary arteries drain into the coronary sinus. Venous sampling, as well as pulmonary artery sampling, will also ignore lactate metabolism in the lungs which drain into the left atrium from bronchial and pulmonary circulations. Turnover rates calculated from either venous or arterial specific activities underestimate true tissue turnover. Correction for either measurement depends on good estimates of blood flows to lactate exchanging and non-exchanging tissue. Equilibration between lactate and pyruvate pools does not invalidate the use of tracers to measure lactate turnover. The (v-a) mode with venous infusion and arterial sampling has advantages for lactate tracer studies.

Arteries↗
PubMed1988

A model for measurement of lactate disappearance with isotopic tracers in the steady state.

1. The irreversible disappearance of lactate carbon from the body (RdL) is commonly calculated from data obtained with a continuous infusion of isotopically labelled lactate tracer. The tracer infusion rate divided by the steady-state lactate specific radioactivity in blood is taken to give the rate of lactate disappearance. 2. Measurement of lactate disappearance is complicated by the fact that it is reversibly converted into pyruvate as well as being irreversibly removed from the system. 3. We analysed a four-compartment model of lactate metabolism, representing blood lactate, tissue lactate and pyruvate carbon pools. 4. The standard method of calculating RdL from the lactate tracer infusion rate divided by the specific radioactivity of lactate was not validated. 5. We found that RdL can be calculated from the infusion rate and the pyruvate specific radioactivity, multiplied by the fraction of the total carbon flow out of pyruvate that goes to lactate. 6. Therefore, if almost all of the pyruvate carbon flows back to lactate, then RdL approaches the tracer infusion rate divided by the pyruvate specific radioactivity. On the other hand, if the rate of oxidation is large in relation to the rate of pyruvate conversion into lactate, than RdL is overestimated when calculated from the pyruvate specific radioactivity. 7. Calculation of RdL with the arterial lactate specific radioactivity results in an underestimate of the true RdL.

Animals↗
PubMed1988

Measuring tracee turnover from tracer specific activity in the steady state.

When a substrate appears in and disappears from an unmeasured (tissue) compartment, the proper sites for tracer infusion and sampling to measure tracee turnover become controversial. We analyze a three-compartment model representing arterial blood, tissue, and venous blood. The desired quantity, tracee turnover, is the ratio of the steady-state infusion rate to tissue specific activity. However, specific activity in the tissue compartment is unknown. We assume infusion of tracer into the arterial pool at a constant rate and consider sampling of specific activity of either blood compartment in the steady state. We obtain estimates of tissue specific activity from measurement of concentrations of tracer and tracee in blood samples in two extreme cases. In case I, tracee is assumed to appear in the venous compartment but to disappear from the tissue pool. Then tissue specific activity is equal to arterial specific activity. In case II, both appearance and disappearance are from the tissue pool. Tissue specific activity is then less than arterial or venous specific activity. We give formulas for the difference in each case. We discuss the relationship of our models to actual tracer experiments and define physiological locations for our three compartments. Appearance of substrates is probably intermediate between our extreme cases. A numerical estimate of turnover for the substrate lactate in resting humans reveals an error bound of approximately 30%. We discuss sites of infusion and sampling consistent with our model, the effects of relaxing some of our modeling constraints, and experimental necessities for getting beyond the steady state.

Algorithms↗
PubMed1982

Oculomotor effects of intermittent conduction block in myasthenia gravis and Guillain-Barré syndrome. An oculographic study with computer simulations.

Five abnormal oculographic patterns were identified in eight patients with either myasthenia gravis or Guillain-Barré syndrome (GBS). These could be differentiated into three intrasaccadic and two postsaccadic abnormalities. From our studies of computer simulations, and considering the established pathophysiology of myasthenia gravis and GBS, we believe that our oculographic findings were a consequence of defects in peripheral neural and neuromuscular conduction, together with a simple adaptive increase in duration of the saccadic burst of central innervation. We conclude that the eye movement abnormalities we observed are explained by intermittent block of peripheral conduction, and suggest that any disease causing intermittent blockage of neural signals to extraocular muscles will produce similar abnormalities of eye movement.

Adolescent↗