Biomedical subjects

W C Hunter

Publications and source records attributed to W C Hunter.

At least 55 records · Page 3Linked to original sources

PubMed1987

Dynamic stiffness measured in central segment of excised rabbit papillary muscles during barium contracture.

The dynamic mechanical behavior of excised rabbit papillary muscles that had been tonically activated by replacing bathing Ca2+ with Ba2+ was studied. Steady activation was used to visualize the dynamic behavior of cardiac myofilaments more clearly than is possible during twitches, which are complicated by the kinetics of excitation-contraction coupling. To avoid artifacts due to damaged ends of the muscle, the length of a central segment, which was defined by 2 tungsten pins inserted through the muscle, was measured. To test the mechanical behavior of the contractured muscles (at 24 degrees C), the central segment length was sinusoidally oscillated (amplitude 1%) at 15 different frequencies (0.05-30 Hz). The dynamic stiffness of the central segment was calculated from the ratio of force response amplitude to length perturbation amplitude. At low frequencies (below 0.4 Hz), stiffness was approximately constant and reflected the force-length relation. However, in a localized range near 1 Hz, there was a distinct drop in the magnitude of dynamic stiffness to approximately half its low-frequency baseline. This range may reflect the dynamics of attachment and detachment of force generators. The frequency of minimum stiffness was consistent among all muscles (1.3 +/- 0.3 Hz). Moreover, no significant change in this frequency was found over the examined range of lengths (90-100% of the segment length that produced maximal developed force) and activation levels (Ba2+ concentration 0.3-1.0 mM). From 2 to 8 Hz, dynamic stiffness appeared to reflect force-velocity properties, but at higher frequencies, another elastic property emerged. At 30 Hz, stiffness was proportional to force, with an apparent series elasticity less than 1.8%. Even though the muscles had only moderate longitudinal inhomogeneity, quantitatively significant (35%) errors would have been introduced had the study relied on total muscle length instead of central segment length.

Animals↗

PubMed1987

Dynamic stiffness of barium-contractured cardiac muscles with different speeds of contraction.

The dynamic stiffness of excised cardiac muscles that would be likely to have different intrinsic speeds of contraction, as judged by previous biochemical reports of their myosin ATPase rates, was compared. This study included muscles from thyrotoxic rabbits and newborn rabbits, rabbit atria, and normal papillary muscles at different temperatures. The usual excitation-contraction coupling process was bypassed by replacing bathing Ca2+ with Ba2+. The ensuring actively maintained contracture allowed us to focus more specifically on the contractile properties of the myofilaments. Dynamic stiffness was determined by sinusoidally oscillating muscle length at many different frequencies over the range 0.05-50 Hz while holding average muscle length at 95% of the systolic length, thus giving maximal developed force. The form of the stiffness modulus spectrum was similar for all muscles studied: stiffness was fairly constant at low frequencies, decreased to a minimum at an intermediate frequency, and then increased steeply, followed by a milder rate of increase over high frequencies. Differences in contraction speed were evident by shifts in the frequencies at which corresponding portions of the stiffness spectrum appeared. The clearest landmark was the frequency where stiffness became minimum (fmin). This varied strongly with temperature (Q10 = 2.9). Compared to normal adult papillary muscles (fmin = 1.2 Hz), fmin was 2.2 times faster in thyrotoxic myocardium, 1.9 times faster in 1-week-old rabbits, and 3.7 times faster in atrial trabeculae. These ratios of functional speed are similar to the corresponding ratios of myosin Ca2+-ATPase activities reported in the literature.

Animals↗

PubMed1986

Time sequential prediction of ventricular-vascular interactions.

A new analytical method (sequential convolution) for describing ventricular-vascular interactions was used to predict instantaneous pressure and flow in four isolated canine left ventricles ejecting into a computer-simulated arterial system. Ventricular pumping ability was described by a load-independent elastance, [E*(t)] combined with a ventricular internal resistance. "Arterial" properties were characterized using a time-based impulse response function that is derived from impedance measurements. Sequential convolution was then used to couple these independent descriptions of ventricular and vascular properties. Predicted pressure-volume trajectories, as well as instantaneous pressures and flows, closely matched the experimental data. Stroke volume, peak pressure, and peak flow were typically within 5% of measured values. This method provides a powerful analytical technique for examining ventricular-vascular interactions and has potential application in evaluating the ventricular-loading effects of more complex in vivo vascular properties.

Animals↗

PubMed1986

End-systolic measures of regional ventricular performance.

Dimension change measures of regional ventricular function, such as absolute or percent wall thickening (delta T or % delta T) or segmental shortening (delta L or % delta L), are highly load dependent. In 16 anesthetized mongrel dogs we assessed use of the end-systolic pressure-thickness and end-systolic pressure-length relationships (ESPTR, ESPLR) as more load-independent measures of regional function. We found that the ESPTR and ESPLR could be measured without detectable baroreceptor-mediated reflex changes in cardiac contractile state. Systemic administration of dobutamine shifted the ESPTR to the right and the ESPLR to the left of control, mainly due to a change in the slope (Ees) of the relationships. Both delta T, % delta T and delta L, % delta L failed to detect the positive inotropic effect of dobutamine because of an associated reduction in preload. With systemic administration of propranolol, ESPTR, ESPLR, delta T, % delta T, and delta L, % delta L detected the negative inotropic effect. Thus systemic propranolol shifted the ESPTR to the left and the ESPLR to the right of control, mainly due to a change in Ees. Regional administration of dobutamine shifted the ESPTR and the ESPLR in the direction of positive contractility in the region receiving the drug, whereas simple dimension change measures of regional function failed to detect the inotropic effect because preload fell and the timing of regional end-systole was altered. With regional propranolol both the ESPTR, ESPLR and simple dimension change measures detected the negative inotropic effect. Thus the ESPTR, ESPLR is a reliable measure of regional ventricular function and may be better than simple dimension change measures of regional function, particularly when loading conditions or the timing of regional systole is altered by an intervention.

Animals↗

PubMed1985

Effect of heart rate on the canine end-systolic pressure-volume relationship.

Although the rate dependence of isolated muscle contractility is well known, the ventricular end-systolic pressure-volume relationship (ESPVR) has been reported to be insensitive to heart rate. To resolve this contradiction, we used an isolated, ejecting canine heart preparation perfused at a constant coronary arterial pressure. Heart rate was changed from 60 to 200 beats/min in steps of 20 beats/min. At least 10 pressure-volume loops under different filling pressures were obtained at each heart rate in each of six hearts. Over a heart rate range from 60 to 120 beats/min, the slope of the ESPVR (Ees) increased significantly from 3.5 +/- 0.4 (SE) to 5.3 +/- 0.6 mm Hg/ml. In the range between 120 and 180 beats/min there was little change in Ees (5.3 +/- 0.6 to 5.4 +/- 0.6 mm Hg/ml), but at 200 beats/min Ees increased slightly to 5.7 +/- 0.5 mm Hg/ml. The volume axis intercept (V0) of the ESPVR changed little over the range of heart rate from 60 to 160 beats/min (10.2 +/- 2 ml to 9.4 +/- 1.3 ml) but increased to 15.2 +/- 1.2 ml at a rate of 200 beats/min. The change in ESPVR with increase in heart rate from 60 to 120 beats/min (i.e., increase in Ees without change in V0) is the same as those seen with a positive inotropic intervention with calcium or cathecholamines, whereas the V0 changes over the range from 160 to 200 beats/min is similar to those seen with regional ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Postextrasystolic potentiation of the isolated canine left ventricle. Relationship to mechanical restitution.

We established, for the isolated, isovolumically beating canine left ventricle, a comprehensive description of postextrasystolic contractile strength (dP/dtmax) as a function of extrasystolic and postextrasystolic stimulus intervals. In contrast to previous studies of postextrasystolic beats in in situ hearts, these isolated ventricles contracted isovolumically so that dP/dtmax was not affected by fluctuations in preload and afterload and was therefore considered to be a reliable index of intrinsic contractility. With the interval preceding extrasystoles constant, postextrasystolic contractile strength increased monoexponentially to a plateau as the interval preceding postextrasystoles lengthened, with a mean time constant (+/- SD) of 182 +/- 44 msec (n = 53). The onset of this increase in postextrasystolic contractile strength coincided with repolarization of the extrasystolic action potential. With the interval preceding postextrasystoles held constant and long (1200 msec), postextrasystolic contractile strength decreased according to a monoexponential function as the interval preceding extrasystoles lengthened [mean time constant (+/- SD) of 176 +/- 18 msec (n = 10)]. These phenomena could be quantitatively summarized by a single equation description of postextrasystolic contractile strength which involved monoexponential functions with one time constant. The mathematical form of this description led us to a simple interpretation of these phenomena in terms of currently proposed excitation-contraction coupling models of the heart.

Animals↗

PubMed1984

Mechanical restitution of isolated perfused canine left ventricles.

We measured cardiac mechanical restitution curves, which describe the time course of recovery of ventricular contractile strength following a steady-state beat. In the first series of experiments, we studied left ventricles that beat isovolumically throughout the experiment, allowing use of dP/dtmax as a reliable index of contractile strength independent of the influence of changing ventricular pre- and afterload. The commencement of mechanical restitution was found to be associated with the onset of electrical diastole; thereafter, contractile strength rose monoexponentially to a plateau that was maintained for test pulse intervals as long as 15 s. The time constant of restitution (typically 245 ms) was independent of priming frequency and ventricular volume. These findings were interpreted in terms of a model of intracellular calcium fluxes within the myocardial cells. In a second series of experiments, we measured mechanical restitution curves from isolated ventricles that ejected against a simulated arterial impedance system. Under this condition, we did not observe the monoexponential time course of mechanical restitution as was measured under isovolumic conditions. The differences between the mechanical restitution curves measured under isovolumic and ejecting conditions were attributed to the influences of changing hemodynamic conditions on dP/dtmax that caused it to be an unreliable index of contractile strength.

Animals↗

PubMed1984

Quantitative comparison of the force-interval relationships of the canine right and left ventricles.

We quantitatively compared the extrasystolic and postextrasystolic responses of the right ventricle and left ventricle of the same heart, which have vastly different geometries, architectures, and muscle masses. We studied nine isolated, supported canine hearts whose right and left ventricles were made to contract isovolumically with balloons placed in both chambers. The ventricles were paced with the following pattern: 20 regularly timed priming stimulations, followed by a test stimulation at a variable test pulse interval, and, finally, by a second test stimulation which was always delivered 1200 msec after the first test pulse. In each heart, approximately 15 different test pulse intervals between 300 and 1200 msec were investigated. Both the maximum developed pressure and maximum rate of pressure development, expressed as a percentage of their steady state values during the priming period were used to quantify the extra- and postextrasystolic responses. For each extrasystolic and postextrasystolic test beat, the normalized response of the right ventricle was plotted vs. that of the left ventricle. The regression line and correlation coefficient between the two were determined. The average result from nine hearts gave a slope of 0.96 +/- 0.05, an intercept of 4.52 +/- 4.05% and a correlation coefficient of 0.995 +/- 0.004. This analysis indicated that, despite the differences in right and left ventricular geometry, architecture, and mass, their force-interval behaviors were nearly identical.

Animals↗

PubMed1983

Systolic mechanical properties of the left ventricle. Effects of volume and contractile state.

To characterize the mechanical properties of the contracting left ventricle, we studied the changes in left ventricular systolic pressure following step-like perturbations (+/- 3 ml) in ventricular volume, using an isovolumically beating, isolated canine heart preparation. Three mechanical properties (elasticity, resistance, and a deactivation effect) were identified. The elastic property differs from the traditional parallel and series elastic elements; it is a time-varying elasticity that includes active and passive effects of volume changes. Furthermore, it could not be represented by a simple time-varying elasticity, but required a second factor to express the dependence of end-systolic elasticity on the timing of the volume step. This effect was represented by a "volume influence factor," which may arise from length-dependent activation. The resistive property appeared to be related to force-velocity behavior of the myocardium. Each mechanical property reacted characteristically to steady state changes in ventricular filling volume or contractile state produced by dobutamine (2-13 micrograms/min). Our findings indicate that elasticity was the property most sensitive to changes in contractile state; these changes increased peak isovolumetric pressure 54% on average, and raised elastic stiffness 40% above control (which was 5.1 mm Hg/ml). Changes in ventricular filling volume only prolonged, but did not alter, the level of elastic stiffness attained at peak pressure. These results support the view that elasticity--or the end-systolic pressure-volume relationship--serves in a given heart to quantify contractility. The "volume influence factor" was not affected by either filling volume or contractile state. Resistance increased in direct proportion with ventricular pressure, but this linear relation was not altered greatly by changes in contractile state or in ventricular filling volume. At 100 mm Hg, ventricular resistance averaged 0.11 mm Hg/ml per sec. Finally, deactivation was greater the later in systole a volume step was imposed, and this pattern was independent of changes in ventricular filling volume and in contractile state.

Animals↗

PubMed1981

Functional consequences of expanded aortic bulb: a model study.

An investigation of the mechanical effects and physiological functions of the dilated ascending aorta of diving mammals was undertaken with mathematic modeling methods. A mathematical model of a prototype (canine) arterial system was constructed and was evaluated by comparing model-predicted pressure and flow wave forms at four vascular locations with published accounts of experimental measurements. The prototype model was modified to serve as a model of the diving mammal arterial system by changing peripheral vascular parameters and by changing the dimensions of the ascending aorta section of the model. This modified model gave a very good simulation of pressure and flow behavior in diving mammal arteries during a dive. Various distribution patterns of compliance addition to the prototype aortic pattern were evaluated as to the effect of these patterns on aortic input properties. It was concluded that the geometric distribution pattern found in diving mammal arteries was optimal with respect to reducing aortic impedance and peak systolic pressure development and thus favored the function of the left ventricle. This mechanical function could represent an important part of the total picture of adaptation to prolonged ischemia.

Animals↗

PubMed1980

Mechanical properties of the ventricle during systole.

The systolic mechanical properties of the ventricular chamber, such as its volume elasticity and apparent viscosity or resistance, provide a useful framework for studying ventricular contraction. During systole, elasticity describes the dependence of pressure generated by the ventricle on chamber volume, while resistance describes changes in pressure related to the rate of ejection. Elastic stiffness increases throughout contraction and is sensitive to changes in inotropic state. Resistance also increases during contraction in parallel with ventricular pressure, but changes in inotropic state do not alter the relation between resistance and pressure. These two mechanical properties offer an insight into the performance of the ventricle as a pump; hence, they may be useful in assessing changes in pump function. This review examines several different approaches to the measurement of elasticity and resistance during systole: one approach lumped all the mechanical properties into a mean value expressed as an average impedance; another focused on elasticity, particularly the maximum elasticity achieved at end-systole; a third approach examined elasticity and resistance at high frequencies of volume oscillation; and the final method utilized a flow-pulse technique to study the variations in both elasticity and resistance throughout systole.

Animals↗

PubMed1979

Significance of protein-bound neuraminic acid levels in patients with prostatic and bladder carcinoma.

The role of plasma N-acetyl neuraminic acid (NANA) level in detection and staging prostatic and bladder carcinomas was evaluated. Multiple determinations were obtained in 73 male subjects, including normal controls, patients with prostatic or bladder carcinoma or with benign prostatic hyperplasia. Patients with prostatic or bladder carcinoma had significantly higher NANA levels than normal individuals. Further, in patients with prostatic carcinoma, NANA values correlated well with both the stage of the disease and the response to therapy.

Humans↗

PubMed1979