Biomedical subjects

W C Hunter

Publications and source records attributed to W C Hunter.

At least 19 recordsLinked to original sources

PubMed1997

Measurements of active myocardial tension under a wide range of physiological loading conditions.

Active tension developed while cardiac muscle shortens has been studied extensively under afterloaded isotonic or isovelocity conditions. However, these are not true in vivo loading conditions. To obtain more physiological loading, we controlled sarcomere length to follow the time courses that we observed previously in a beating canine left ventricle. Sarcomere length was measured by laser diffraction in 12 rat cardiac trabeculae, superfused with Krebs-Henseleit solution (25 degrees C; [Ca] = 1.5 mM). Force was measured by a silicon strain gauge. Sarcomere length time courses were scaled slightly in time to account for temperature and species differences. We examined the relationships between active tension and sarcomere length under loading observed over a wide range of left ventricular preloads and afterloads, and at two sites. Under all loading conditions, active tension was not isotonic but declined steadily throughout the ejection period. While there were major differences in peak tension dependent on loading conditions and the incidence of 'pre-ejection' sarcomere shortening, these factors did not influence the relationship between sarcomere length and peak active tension. This study provides excellent illustrations of the potential differences in stress (1) within a ventricular wall, and (2) under different operating conditions. Moreover, it provides data for developing models of fiber contraction to be synthesized into a whole heart for predicting potential differences in stress at all sites and under all loading conditions.

Animals↗

PubMed1997

Anterior and posterior left ventricular sarcomere lengths behave similarly during ejection.

Previous studies of regional differences in myocardial deformation between the anterior and posterior walls of the canine left ventricle were based on strain, which is not an absolute measure of deformation. We thus compared sarcomere lengths at anterior and posterior sites during ejection in isolated dog hearts. Cineradiographic imaging of regional deformation with radiopaque markers implanted near the midwall in five hearts and just below the epicardium in six hearts, combined with postmortem histology, allowed sarcomere length reconstruction throughout the cardiac cycle. The amount of sarcomere shortening accompanying left ventricular ejection was similar in both walls of the left ventricle for sarcomeres located at epicardial and midwall sites. The mean sarcomere length (taken at the middle of the ejecting range) was also similar between the anterior and posterior sites when averaged over all hearts. The similarity of sarcomere function held not only at end systole but throughout ejection and over wide ranges of ventricular pre- and afterloads. Hence functional measurements of relative myocardial shortening may not be indicative of regional sarcomere length heterogeneity.

Animals↗

PubMed1995

Three-dimensional myocardial deformations: calculation with displacement field fitting to tagged MR images.

PURPOSE: To reconstruct three-dimensional (3D) myocardial deformations from orthogonal sets of parallel-tagged magnetic resonance (MR) images. MATERIALS AND METHODS: Displacement information in the direction normal to the undeformed tag planes was obtained at points along tag lines. Three independent sets of one-dimensional displacement data were used to fit an analytical series expression to describe 3D displacement as a function of deformed position. The technique was demonstrated with computer-generated models of the deformed left ventricle with data from healthy human volunteers. RESULTS: Model deformations were reconstructed with a 3D tracking error of less than 0.3 mm. Error between estimated and observed one-dimensional displacements along the tags in 10 human subjects was 0.00 mm +/- 0.36 (mean +/- standard deviation). Robustness to noise in the tag displacement data was demonstrated by using a Monte Carlo simulation. CONCLUSION: The combination of rapidly acquired parallel-tagged MR images and field-fitting analysis is a valuable tool in cardiac mechanics research and in the clinical assessment of cardiac mechanical function.

Computer Simulation↗

PubMed1995

Force, not sarcomere length, correlates with prolongation of isosarcometric contraction.

Recent studies have emphasized the importance of the late systolic phase for understanding ventricular ejection. To examine the myocardial factors controlling this phase, we studied the timing of twitch contraction in nine excised rat trabeculae contracting isosarcometrically. By varying both sarcomere length (SL) and extracellular Ca2+ concentration ([Ca2+]) we determined which of these factors or the developed peak twitch force correlated better with the prolongation of contraction. We focused on the period from just before the peak of force to the time of half relaxation. SL was measured by laser diffraction and kept constant using adaptive control. Peak twitch force was the factor most tightly correlated with prolongation of contraction: as force rose from 10 to 100 mN/mm2, duration tripled from 100 to 300 ms. When the trend with force was removed, however, no separate influence of SL remained. Increase in [Ca2+]o abbreviated contraction equally at all force levels. Prolongation of late systolic contraction was also highly correlated with prolongation of the time constant for late relaxation, suggesting a common mechanism by which peak twitch force lengthens the entire subsequent time course of a twitch. We hypothesize that 1) increased force correlates with prolonged Ca2+ binding to troponin-C, and/or 2) attached cross bridges act cooperatively to oppose the inhibiting effects of tropomyosin as Ca2+ is lost from the thin filaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Macroscopic three-dimensional motion patterns of the left ventricle.

The pattern of displacements in the left ventricle (LV) can be described by 13 modes of motion and deformation. Three functional modes of deformation are essential for ejection: a decrease in cavity volume, torsion, and ellipticalization. Four additional modes are used to describe asymmetric deformation. Six modes of rigid body motion describe rotation and translation. In the LV 14-20 radiopaque markers were inserted in the wall of the LV. They were distributed more or less evenly from base to apex and around the circumference. Torsion and volume changes require the definition of a cardiac coordinate system. The point at which ejection focuses is used as the origin, and the torsion axis is used as the z-axis. In the present study the coordinate system was positioned objectively by a least squares fit of the kinematic model to the measured motion of markers. In five dogs in the control state the kinematic parameters were determined as a function of time for all 13 modes. The torsion axis was displaced 4 +/- 2 mm (mean +/- sd) from the center of the cross-section of the LV towards the lateral free wall. The direction of the torsion axis closely coincided with anatomical landmarks at the apex and base. During systole, a unique relation was found between the ratio of cavity volume to wall volume and torsion. This relation was universal to all LVs, the cylinder-symmetric mathematical model of cardiac mechanics inclusive. In diastole the patterns of deformation seem less universal and reproducible.

Animals↗

PubMed1993

Effects of pentobarbital on inotropic state of isolated canine left ventricle.

Although pentobarbital has been found to depress myocardial function, the magnitude of its direct effects on ventricular contraction at anesthetic concentrations has not been well quantified. The direct effects of pentobarbital on left ventricular function were measured by employing an isolated canine heart preparation with a blood oxygenator. Seven hearts were perfused with blood, dextran, and perfluorochemical artificial blood. Ventricular function was evaluated using the slope of the end-systolic pressure-volume relationship (Ees) and the maximal rate of pressure development (dP/dtmax) in ventricles contracting isovolumically in control, after a low dose (13 micrograms/ml), and after a high dose (48 micrograms/ml) of pentobarbital. These concentrations represent one-half and two times the typical value (25 micrograms/ml) found to produce anesthesia in canines (assessed by tail clamp or blink reflex). The low dose of pentobarbital did not produce clear-cut depression in contractile function. The high dose of pentobarbital produced significant reductions of Ees, and dP/dtmax: Ees decreased 29%, from a control of 4.30 +/- 0.84 to 3.05 +/- 0.49 mmHg/ml and dP/dtmax decreased 24%, from a control of 909 +/- 148 to 695 +/- 173 mmHg/s. Thus, the threshold for the direct depressant effect of pentobarbital on ventricular function falls within the range of half to double the typically-reported anesthetic concentrations.

Animals↗

PubMed1993

Ventricular stroke work and efficiency both remain nearly optimal despite altered vascular loading.

Recent clinical and animal studies have suggested that ventricular-vascular coupling normally operates at either optimal ventricular efficiency (EFF = stroke work/myocardial oxygen consumption) or stroke work (SW) and that efficiency in particular is compromised by cardiac dysfunction. These distinctions between coupling states at maximal work vs. efficiency are largely based on theoretical models. To date, there are few direct experimental data defining optimal conditions for each parameter, respectively, in the same heart or tests of whether changes from these conditions must produce significant declines in both parameters. Therefore, 10 isolated blood-perfused canine hearts were studied at varying contractilities, with the heart ejecting into a simulated three-element Windkessel model of arterial impedance. For a given inotropic state [indexed by the slope of the end-systolic pressure-volume relationship (Ees)], myocardial oxygen consumption and SW were measured over a broad range of afterload resistances. The latter was indexed by the effective arterial elastance (Ea) and ventricular-vascular interaction expressed by the ratio of Ea to Ees (Ea/Ees). On average, maximal SW occurred at Ea/Ees = 0.80 +/- 0.16, whereas EFF was maximal at Ea/Ees = 0.70 +/- 0.15 (P < 0.01). However, these differences were small, and both SW and EFF were > or = 90% of their respective optima over a broad overlapping range of Ea-to-Ees ratios (0.3-1.3, corresponds with ejection fractions ranging from approximately 40 to 80%). These data show that both SW and efficiency are nearly maximal under many conditions of ventricular-vascular interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Similarities between dynamic elastance of left ventricular chamber and papillary muscle of rabbit heart.

The frequency-dependent dynamic elastance of the left ventricle (LV) of isolated rabbit heart was determined and compared with dynamic stiffness of excised rabbit papillary muscle. Comparison was made in three states: 1) relaxed, 2) BaCl2 contracture, and 3) rigor. Dynamic chamber elastance was determined by pressure-to-volume ratio at 12 frequencies of sinusoidal volume variation between 0.1 and 30 Hz. Dynamic elastance during BaCl2 contracture was distinctly different from that during either relaxed or rigor states. Characteristics of BaCl2 contracture were 1) as frequency increased, polar plot of real and imaginary elastance showed a progressively opening clockwise spiral that tended eventually to become tangent to the apogee of a semi-circle by 30 Hz; 2) modulus spectrum exhibited asymptotes at low and high frequencies with an intervening dip to a minimum at 1.25 Hz; and 3) phase showed a sharp transition at dip frequency from small negative values at lower frequencies to large positive values at intermediate frequencies and then declined at highest frequencies. There was little dependence of dynamic elastance on frequency in both relaxed and rigor states. Dynamic muscle stiffness exhibited all features of dynamic chamber elastance in all three states. We concluded that dynamic elements responsible for myofiber stiffness were also responsible for LV chamber elastance. Furthermore, it was possible to describe and interpret dynamic chamber elastance and muscle stiffness with a common model based on muscle cross-bridge theory. This model did a reasonable job of reproducing all important features of experimentally observed LV chamber elastance and muscle stiffness. Thus dynamic homologies between chamber and muscle were established in experimental data and in the fact that a single interpretive model served equally well for both chamber elastance and muscle stiffness.

Animals↗

PubMed1993

Impact of ejection on magnitude and time course of ventricular pressure-generating capacity.

This study focuses on elucidating how ventricular afterloading conditions affect the time course of change of left ventricular pressure (LVP) throughout the cardiac cycle, with particular emphasis on revealing specific limitations in the time-varying elastance model of ventricular dynamics. Studies were performed in eight isolated canine hearts ejecting into a simulated windkessel afterload. LVP waves measured (LVPm) during ejection were compared with those predicted (LVPpred) according to the elastance theory. LVPm exceeded LVPpred from a time point shortly after the onset of ejection to the end of the beat. The instantaneous difference between LVPm and LVPpred increased steadily as ejection proceeded and reached between 45 and 65 mmHg near end ejection. This was in large part due to an average 35-ms prolongation of the time to end systole (tes) in ejecting compared with isovolumic beats. The time constant of relaxation was decreased on ejecting beats so that, despite the marked prolongation of tes, the overall duration of ejecting contractions was not greater than that of isovolumic beats. The results demonstrate a marked ejection-mediated enhancement and prolongation of ventricular pressure-generating capacity during the ejection phase of the cardiac cycle with concomitant acceleration of relaxation. None of these factors are accounted for by the time-varying elastance theory.

Animals↗

PubMed1992

Description of the deformation of the left ventricle by a kinematic model.

A model of left ventricular (LV) kinematics is essential to identify the fundamental physiological modes of LV deformation during a complete cardiac cycle as observed from the motion of a finite number of markers embedded in the LV wall. Kinematics can be described by a number of modes of motion and deformation in succession. An obvious mode of LV deformation is the ejection of cavity volume while the wall thickens. In the more sophisticated model of LV kinematics developed here, seven time-dependent parameters were used to describe not only volume change but also torsion and shape changes throughout the cardiac cycle. Rigid-body motion required another six parameters. The kinematic model employed a deformation field that had no singularities within the myocardium, and all parameters describing the modes of deformation were dimensionless. Note that torsion, volume and symmetric shape changes all require the definition of a cardiac coordinate system, which has generally been related to the measured cardiac geometry by reference to approximate anatomical landmarks. However, in the present study the coordinate system was positioned objectively by a least-squares fit of the kinematic model to the measured motion of markers. Theoretically, at least five markers are needed to find a unique set of parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Finite extension and torsion of papillary muscles: a theoretical framework.

We present a new analytical solution for the finite extension and torsion of a nonlinearly pseudoelastic, homogeneous, transversely isotropic, incompressible, solid circular cylinder. This solution can be used to guide the performance and interpretation of experiments, and to identify a specific functional form of a three-dimensional constitutive relation directly from data. We submit, therefore, that this solution can be used by experimentalists to quantify the multiaxial constitutive relations, including shear, of both passive and tonically activated papillary muscles for the first time.

Animals↗

PubMed1992

Comparison between the effects of 2-3 butanedione monoxime (BDM) and calcium chloride on myocardial oxygen consumption.

The agent 2,3-butanedione monoxime (BDM) has been reported to reduce the sensitivity of myofilament force development to calcium ions, without affecting the calcium transient in myocardium. One would predict, therefore, that BDM should reduce the contractile state of the heart without reducing the amount of oxygen that is consumed to fuel the process of excitation-contraction coupling. The purpose of the present experiment was to test this hypothesis using isovolumically contracting, isolated, blood perfused canine hearts during beta-blockade induced by continuous intra-coronary infusion of propranolol (1 mg/h). Contractile state was increased in seven hearts by CaCl2 infusion. Subsequently, while the CaCl2 infusion was continued at the highest rate, contractile state was reduced by BDM infusion. At each contractile state, we measured the left-ventricular end-systolic pressure-volume relation (ESPVR), the relation between myocardial oxygen consumption and its mechanical correlate, pressure-volume area (MVO2 vs PVA), and the duration of the LV pressure waveform. Contractile state was quantified by interpolated developed pressure at a reference ventricular volume of 25 ml (P25). BDM infusion (0.5-7 mM) caused a dose-dependent reduction in contractile state (50% reduction in P25 at 2.4 +/- 0.3 mM), and a dose-independent increase in coronary blood flow. Furthermore, BDM significantly reduced the duration of the pressure waveform up to 40% at the highest rate of BDM infusion compared to the pressure waveform duration measured at maximum CaCl2 infusion. We observed a direct relationship between MVO2 of the mechanically unloaded heart and contractility; this relation was unaffected by BDM infusion (P > 0.3). The slope of the MVO2-PVA relation decreased with increases in contractile state, but this decrease was unaffected by BDM (P > or = 0.4). We conclude that in the isolated canine heart, BDM does not act energetically as expected for a myofibrillar calcium desensitizing agent.

Animals↗

PubMed1992

A method to reconstruct myocardial sarcomere lengths and orientations at transmural sites in beating canine hearts.

The ability to measure cyclic changes in myocardial sarcomere lengths and orientations during cardiac ejection and filling would improve our understanding of how the cellular processes of contraction relate to the pumping of the whole heart. Previously, only postmortem sarcomere measurements were possible after arresting the heart in one state and fixing it for histology. By combining such histological measurements with direct observations of the deformation experienced by the same myocardial region while the heart was beating, we have developed a method to reconstruct sarcomere lengths and orientations throughout the cardiac cycle and at several transmural layers. A set of small (1 mm) radiopaque beads was implanted in approximately 1 cm3 of the left ventricular free wall. Using biplane cineradiography, we tracked the motion of these markers through various cardiac cycles. To quantify local myocardial deformation (as revealed by the relative motion of the markers), we calculated the local deformation gradient tensors. As the heart deforms, these describe how any short vectorial line segment alters its length and orientation relative to a reference state. Specifically, by choosing the reference state to be the arrested and fixed heart and by measuring the sarcomere vector in that state, we could then use the deformation gradient tensors to reconstruct the sarcomere vector that would exist in the beating heart. As ventricular chamber volume varied over its normal range of operation, the range of reconstructed sarcomere lengths (approximately 1.7-2.4 microns) was comparable to other histological studies and to measurements of sarcomere length in excised papillary muscles or trabeculae. The pattern of sarcomere length changes was markedly different, however, during ejection vs. filling.

Animals↗

PubMed1992

Effects of calcium and EMD-53998 on oxygen consumption in isolated canine hearts.

BACKGROUND: Most positive inotropic agents increase cardiac contractility by increasing the amount of Ca2+ cycled with each beat. The additional amount of oxygen that is consumed by the heart to cycle this additional Ca2+ is believed to reduce myocardial efficiency. On the other hand, it has been suggested that the agent EMD-53998 increases the Ca2+ sensitivity of the contractile proteins without affecting the intracellular Ca2+ transient in cardiac muscle. Therefore, application of this agent may increase cardiac contractility without decreasing myocardial efficiency. The purpose of the present study was to test this hypothesis. METHODS AND RESULTS: We measured myocardial oxygen consumption (MVO2) in six isolated, isovolumically beating blood-perfused canine hearts. The hearts were paced at 120 beats per minute. Contractility was varied in each heart by infusion of either CaCl2 or EMD-53998. With infusion of either agent, MVO2 was a linearly proportional function of contractility. No significant difference between CaCl2 and EMD-53998 could be detected in the interrelation between contractility and MVO2. CONCLUSIONS: We conclude that the "calcium-sensitizing agent" EMD-53998 is a potent positive inotropic agent in the isolated, blood-perfused canine heart. However, EMD-53998 does not provide an energetic advantage over currently used positive inotropic agents.

Animals↗

PubMed1992

Alterations in left ventricular mechanics, energetics, and contractile reserve in experimental heart failure.

The contributions of changes in primary systolic and diastolic properties, limitations of contractile reserve, and alterations in energy efficiency to the left ventricular dysfunction seen with chronic pacing tachycardia were investigated. Seven dogs (heart failure group) were ventricularly paced at 250 beats per minute for 26.3 +/- 2.9 days and compared with a separate control group (n = 8). STudies were performed with isolated, metabolically supported hearts coupled to a computer-controlled loading system. Pressure-volume relations and myocardial oxygen consumption (MVO2) were measured to assess chamber systolic and diastolic properties and efficiency (relation between MVO2 and pressure-volume area [PVA]). Systolic function was reduced in failure hearts versus controls as assessed by the slope of the end-systolic pressure-volume relation (1.29 +/- 0.94 versus 2.71 +/- 0.98 mm Hg/ml, p less than 0.01) and lowered end-systolic stiffness at a matched stress (956.1 +/- 123.5 versus 1,401.7 +/- 431.7 g/cm2, p less than 0.05). Diastolic chamber and myocardial stiffness were unaltered in failure hearts, but the unstressed diastolic-arrested volume was significantly larger (33.3 +/- 3.9 versus 21.9 +/- 7.6 ml, p less than 0.01). Inotropic response to increased heart rate and exogenous beta-adrenergic stimulation (dobutamine HCl) was significantly impaired in failure compared with control hearts. Most interestingly, failure hearts had a lowered slope of the MVO2-PVA relation (2.1 +/- 1.1 versus 2.9 +/- 1.4 ml O2.mm Hg-1.ml-1.100 g left ventricle-1, p less than 0.001), indicating increased efficiency of chemomechanical energy conversion. The y intercept of the MVO2-PVA relation, which reflects oxygen costs of basal metabolism and excitation-contraction coupling, was unchanged in the two groups despite decreased contractility of the heart failure hearts. These results demonstrate reduced chamber and myocardial contractility, dilatation without alteration of passive myocardial properties, impaired contractile reserve, and novel alterations in cardiac efficiency in this model of heart failure.

Animals↗

PubMed1992

Basal metabolism adds a significant offset to unloaded myocardial oxygen consumption per minute.

Myocardial oxygen consumption (MVO2) includes components for 1) mechanical energy generation, 2) activation, and 3) basal metabolism. Whereas the first two components are expected to increase in proportion with heart rate, a significant basal level of metabolism would consume oxygen even if the heart rate were zero. Contrary to this expectation, however, a previous study reported that, during unloaded beats, MVO2 per beat (which includes basal metabolism) was independent of heart rate. Accordingly, unloaded MVO2 per minute would extrapolate to zero at zero heart rate; this result is unexpected considering basal metabolism. To resolve this inconsistency, we varied heart rate over a wide range after inducing atrioventricular block in eight isolated cross-circulated canine hearts that contracted isovolumically. We examined whether a term representing rate-independent basal metabolism was needed to describe MVO2 per minute. Mechanical energy generated by the left ventricle was evaluated from the pressure-volume area, which was altered by changing isovolumic ventricular volume over at least five levels at each heart rate. Contractility, evaluated by the slope of the end-systolic pressure-volume relation, did not vary significantly with heart rate in this study. In contrast to the previous report, unloaded MVO2 per beat (i.e., MVO2 extrapolated to a pressure-volume area of zero) was not constant but fell monotonically with increases in heart rate in every heart. We considered that this trend was caused by a significant rate-independent basal level of MVO2 per minute. Multiple linear regression analysis confirmed that this rate-independent basal term differed significantly from zero in seven of the eight hearts studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Contractile strength and mechanical efficiency of left ventricle are enhanced by physiological afterload.

Recent studies have shown that at the same endsystolic volume, ejecting beats can achieve a higher end-systolic pressure than isovolumic beats. The purpose of this study was to assess the metabolic cost, in terms of oxygen consumption (MVO2), and efficiency, in terms of the relation between MVO2 and pressure-volume area (PVA), of this increase in strength during ejection. The slope of the end-systolic pressure-volume relation (ESPVR) (Ees) was greater during ejecting than isovolumic contractions when ejection fraction (EF) was greater than approximately 30%, indicating an increase in contractile strength. The difference in Ees between the two modes of contraction was as much as 30% at EFs of 60%. In contrast, the slope of the MVO2-PVA relation was less during ejecting than isovolumic contractions, indicating a decrease in MVO2 at any given PVA. The difference in slope was as much as 20% at EFs of 60%. Thus afterload conditions, allowing substantial fiber shortening, shift the ESPVR toward greater contractile strength and increase the metabolic efficiency when viewed in terms of the relation between MVO2 and total mechanical energy generation (PVA) by the ventricle. This may reflect an energetically favorable effect of shortening on muscle force-generating capability.

Animals↗

PubMed1991

Estimated time course of Ca2+ bound to troponin C during relaxation in isolated cardiac muscle.

We present a mechanical assay for estimating the time course of Ca2+ bound to low-affinity sites on troponin C (TnC) in twitching rabbit papillary muscle. The assay is based on a theoretical correlation between the rate of force redevelopment after detachment of all cross-bridges and the amount of Ca2+ bound to TnC. Experimentally, we applied length impulses at different times to detach all cross-bridges; the initial rate of force redevelopment after each impulse was taken as an index of bound Ca2+ at that time. Under control conditions, the magnitude of this index decreased to 10% of its maximum during early relaxation, when force had declined only slightly 78 +/- 12% of its peak isometric value. The time course of this index was examined after addition of either isoproterenol or ryanodine, which are known to shorten and prolong, respectively, the intracellular free Ca2+ transient. As expected, changes previously reported in the free Ca2+ time course were qualitatively reflected in the time course of the bound Ca2+ index. We conclude that this index constitutes a reasonable method for estimating the time course of bound Ca2+ and that bound Ca2+ declines well ahead of force in isometrically contracting rabbit myocardium at 24 degrees C.

Animals↗