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Biomedical subjects

L E Ford

Publications and source records attributed to L E Ford.

At least 37 records · Page 2Linked to original sources
PubMed1992

Changes in valvular resistance, power dissipation and myocardial reserve with aortic valvuloplasty.

Balloon aortic valvuloplasty results in small changes in valve area with great symptomatic improvement in some patients, while others have little relief with greater increases in valve area. Alternative indices to valve area may help explain this clinical discrepancy. A calculation of valve area does not provide a means of assessing the load imposed by a stenotic valve, while the complementary index valve resistance, defined as the quotient of mean pressure difference divided by flow, allows many other hemodynamic calculations and may provide an additional measure of the hemodynamic importance of valvular obstructions. To assess the value of these calculations, we studied hemodynamic changes in thirty elderly patients undergoing valvuloplasty for aortic stenosis. The valve area, as calculated by the Gorlin formula, increased by an average 67% (0.59 cm2 to 0.95 cm2), while hemodynamic resistance decreased by an average 52% (453 to 207 dyne.sec.cm5). The values of resistance were used to predict pressure gradients and work loads at different cardiac outputs. The increase in myocardial reserve with valvuloplasty was calculated as the increase in cardiac output that could be achieved at the pre-valvuloplasty value of either total ventricular pressure or ventricular work. These calculations assumed that valvular resistance did not change with cardiac output and that peripheral resistance varied inversely to cardiac output so as to maintain a constant aortic (systemic) pressure. The increase in myocardial reserve was 18% when ventricular work rate was the limiting factor, and 103% when pressure was limiting. The increase in reserve may be closer to the higher value since the myocardial work rate is probably not limited by myocardial energy in the absence of coronary artery disease. Four patients who did not do well clinically were characterized by small increases in reserve, either because of inadequate dilatation of the valve or because the original stenosis was not severe. Valve resistance, myocardial reserve, and ventricular work may be calculated using standard hemodynamic measurements. In conjunction with aortic valve area, these indices provide significant complimentary information and may further elucidate the hemodynamic consequences of valvular obstruction.

Aged↗
PubMed1991

Effect of osmotic compression on the force-velocity properties of glycerinated rabbit skeletal muscle cells.

The force-velocity relations of single glycerinated rabbit psoas muscle fibers at 5 degrees C were studied at maximum and half-maximum activation in the presence of 0 (control) and 39-145 g/liter dextran T-70. Resting fiber diameter decreased progressively to approximately 70% of the nondextran control as the dextran concentration was increased. Isometric force at full activation increased to a maximum of 136% of control at 111 g/liter dextran and then fell to 80% of control in 145 g/liter dextran. Maximum velocity, which fell to 49% of the control value in the highest concentration of dextran, was nearly constant at approximately 65% control over the range of 58-111 g/liter dextran. Relative maximum power, which gives an estimate of changes in intermediate velocity, was not significantly reduced by dextran concentrations up to 76 g/liter, but then fell progressively to 62% of control in the highest concentration of dextran. At half-maximum activation, maximum velocity and relative maximum power were not significantly different from the values at full activation. The results obtained at partial activation indicate that the decline of velocity seen in the presence of dextran is not due to a passive internal load and that the dextran does not cause a viscous resistance to shortening. The increased velocity in the absence of dextran can be explained by the reduced ability of cross-bridges to resist shortening, as proposed by Goldman (1987. Biophys. J. 51:57).

Animals↗
PubMed1991

Shortening velocity and power output of skinned muscle fibers from mammals having a 25,000-fold range of body mass.

The shortening velocities of single, skinned, fast and slow skeletal muscle fibers were measured at 5-6 degrees C in five animal species having a 25,000-fold range of body size (mouse, rat, rabbit, sheep, and cow). While fiber diameter and isometric force showed no dependence on animal body size, maximum shortening velocity in both fast and slow fibers and maximum power output in fast fibers were found to vary with the -1/8 power of body size. Maximum power output in slow fibers showed a slightly greater (-1/5 power) dependence on body size. The isometric force produced by the fibers was correlated (r = 0.74) inversely with fiber diameter. For all sizes of animal the average maximum velocity was 1.7 times faster in fast fibers than in slow fibers. The large difference in mechanical properties found between fibers from large and small animals suggests that properties of the contractile proteins vary in a systematic manner with the body size. These size-dependent changes can be used to study the correlations of structure and function of these proteins. Experimental results also suggest that the different metabolic rates observed in different sizes of animals could be accounted for, at least in part, by the difference in the properties of the contractile proteins.

Animals↗
PubMed1991

Effects of hypoxia and hypercapnia on the force-velocity relation of rabbit myocardium.

The separate effects of hypoxia and hypercapnia on the force-velocity relation of rabbit myocardium were compared in 10 papillary or trabecular muscles superfused using control (95% O2-5% CO2), hypoxic (18% O2), and hypercapnic (20% CO2) physiological salt solutions. This level of hypoxia did not irreversibly damage the muscles and reduced peak isometric force by 53 +/- 11%. The level of hypercapnia was chosen to match the force depression (50 +/- 12%) produced by hypoxia. Multiple force-velocity points were measured by applying critically damped isotonic force steps at 90% of the time to peak isometric force and at the time to 50% peak isometric force. These points defined the force-velocity relation and maximum velocity of shortening, the extrapolated isometric force, and the maximum power of nonpotentiated and postextrasytolic potentiated contractions. Hypoxia and hypercapnia reduced maximum force and maximum power nearly equally. Maximum velocity of shortening decreased more during hypoxia (21 +/- 12%) than during hypercapnia (12 +/- 9%) (p less than 0.01). Postextrasystolic potentiation completely reversed the reduction of maximum velocity of shortening during hypercapnia but not during hypoxia. A 6% internal load could account for the reduction in maximum velocity of shortening during hypercapnia and all but 9% of the reduction in maximum velocity of shortening during hypoxia. The relative time course of the force-velocity relation was not altered by either hypoxia or hypercapnia. We conclude that hypercapnia reduces the effect of activation because increased activation (by postextrasystolic potentiation) restored the force-velocity relation and maximum velocity of shortening to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hemodynamic resistance as a measure of functional impairment in aortic valvular stenosis.

Calculated valve area depicts anatomical stenosis but does not quantify hemodynamic impairment. We propose that hemodynamic resistance, defined as the mean pressure gradient across the valve divided by mean flow rate during systolic ejection, gives a better indication of hemodynamic obstruction. This index was compared with Gorlin valve area in 40 patients with aortic stenosis. Calculated area ranged from 0.22 to 1.26 cm2, and mean transvalvular resistance ranged from 117 to 1,244 dyne.sec.cm-5. In general, resistance varied inversely with calculated area, but there was substantial variation about the mean relation. All of the variation could be accounted for by variations in the pressure gradients at each value of calculated area. Resistance was higher in proportion to area when flow and pressure gradient were high. Analysis of five published studies of a total of 83 valves showed that calculated area changed at least three times more than resistance when pressure gradient was varied. The utility of resistance as an index of stenosis is demonstrated by example calculations that show how during exercise a stenotic valve increases the ventricular work rate out of proportion to the work done on the peripheral resistance. These calculations are possible because hemodynamic resistance defines functional impairment in units commonly used for quantification of opposition to flow. Furthermore, resistance appears to be less dependent than area on conditions of measurement and does not require an empirical constant.

Aortic Valve↗
PubMed1989

Comparison of the effects of different inotropic interventions on force, velocity, and power in rabbit myocardium.

To gain some insight into inotropic mechanisms, we compared the effects of several classes of inotropic interventions on the isometric twitch and force-velocity properties of isolated rabbit myocardium. Postextrasystolic potentiation was chosen as one of the interventions in the belief that its onset is so rapid that it would be unlikely to cause substantial chemical changes in the contractile proteins and that most of the effects would be due to changes in the level of activation. The effects of a digitalis analogue (acetylstrophanthidin), an adrenergic agent (isoproterenol), and a methylxanthine (caffeine) were then compared with those of postextrasystolic potentiation. The conditions were chosen so that each agent caused a twofold increase in twitch force. Acetylstrophanthidin and postextrasystolic potentiation caused twitch force to increase with only a slight (11%) decrease in time to peak force. Isoproterenol caused the peak of the twitch to occur substantially (40%) earlier with marked abbreviation of the twitch. Caffeine had the opposite effect: time to peak force was delayed (by 60%), and the twitch was markedly prolonged. In contrast to the marked differences in the time course of the twitch, there was no significant difference between the instantaneous force-velocity curves obtained with the different interventions. All four interventions caused maximum velocity to increase slightly (1-9%) and maximum power to increase only slightly more than twitch force (5-21%). All of the changes observed can be accounted for by changes in activation, either by an increase in the amount of calcium released into the myofilament space or by a change in the sensitivity of the myofilaments to calcium. There was no need to postulate direct changes in the contractile machinery to account for these results.

Animals↗
PubMed1988

Heat changes during transient tension responses to small releases in active frog muscle.

Tension and heat production were measured in frog sartorius muscles in response to small shortening ramps (releases) at high and moderate speed. Transient tension responses to fast releases (0.1 to 0.4 mm in 1 or 4 ms) were similar to the tension transients length-clamped single fibers. Tension time courses during releases at 25 mm/s were like fiber responses calculated from the first two phases of the step responses (Ford et al., 1977). We conclude that similar crossbridge transitions produce tension transients observed in whole muscles and single fibers. Heat was absorbed during rapid tension recovery after fast releases and during the later part of releases at 25 mm/s. Variation of heat absorption with release size was compared with that of crossbridge movement predicted by the Huxley-Simmons hypothesis of force generation (Huxley and Simmons, 1971). Agreement between the two supports the conclusion that heat is absorbed by the crossbridge transitions responsible for rapid tension recovery after release. The results indicate that the entropy change of these transitions is positive.

Animals↗
PubMed1987

The kinetics of heat production in response to active shortening in frog skeletal muscle.

1. Tension and heat production were measured at 0 degree C in sartorius muscles from Rana temporaria in response to two extents of shortening at five velocities. Shortening was from approximately 2.4 to 2.2 microns, 2.4 to 2.3 microns and 2.3 to 2.2 micron at velocities per half-sarcomere from 0.2 to 1.56 micron s-1. 2. Tension became approximately constant at all velocities. Records of heat rate obtained by differentiating traces from which thermoelastic heat had been subtracted became negative early in shortening and then rose. Heat rate became constant during shortening only at the lowest velocity and was still rising at the end of shortening at higher velocities. The highest heat rate occurred at the end of shortening at the two highest velocities. At the end of shortening at all velocities heat rate gradually approached the isometric level measured at the short length, the half-time for decline being largest following the slowest larger shortening. 3. Heat produced as a consequence of shortening but not associated with tension recovery was determined by subtracting shortening heat measured in response to two extents of shortening to the same muscle length. The differences in shortening heat continued to increase after shortening ended, and more of the extra heat produced in response to shortening appeared after the end of rapid shortening than during shortening itself. 4. Shortening heat coefficients calculated in different ways were similar to coefficients determined in previous studies. Coefficients calculated from measurements that excluded heat produced by tension recovery and allowed for continued production of heat by processes initiated by shortening were found to increase linearly with the force maintained during shortening. 5. The results show that the kinetics of heat production during and after shortening are very sensitive to the speed of shortening and that steady rates of energy liberation are not attained during shortening of less than or equal to 10% of muscle length at velocities greater than or equal to 12% of maximum velocity.

Animals↗
PubMed1987

Force, velocity, and power changes during normal and potentiated contractions of cat papillary muscle.

The instantaneous force-velocity relations of cat papillary muscles were studied at different times in the twitch in normal and in postextrasystolic potentiated contractions. Fourteen to sixteen different loads were used to define each of the force-velocity curves. The curves were fitted by a least-squares procedure to the hyperbolic (Hill equation). The hyperbolae were extrapolated to obtain maximum velocity and isometric force and interpolated to obtain maximum power. All three of these values rose more quickly than developed force. Maximum velocity reached 77% of its peak at the earliest time studied, 20-25% of the time to peak force. Developed force achieved 22% of its final value at this time, while extrapolated isometric force and maximum power both reached 44% of their peak values. Postextrasystolic potentiation sufficient to produce a 1.5 to twofold increase in peak developed force produced less than a 20% increase in extrapolated maximum velocity. The results can be interpreted in terms of a model in which the maximum velocity of the contractile elements remains constant during the twitch. Variation in maximum velocity is attributed to a small internal load, equivalent to 6% of twitch force. Since maximum velocity is relatively constant, it does not give a good measure of changes in the force-velocity curves. By contrast, the extrapolated isometric force and maximum power are much more sensitive to changes in the force-velocity curves, and they vary in proportion to each other. The advantage of using interpolated maximum power rather than isometric force to define changes in the curves is that it can be normalized to muscle mass.

Animals↗
PubMed1986

The thermoelastic effect in rigor muscle of the frog.

Small length changes were imposed on pairs of sartorius muscles from Rana temporaria and Rana pipiens in rigor and the mechanical and thermal responses studied. Rigor was induced by soaking the muscles overnight at 0 degrees C in a physiological salt solution containing 1.5 mM sodium azide and 0.4 mM sodium iodoacetate. Tension was measured at both the tibial and the pelvic ends of the preparation. Muscles were held at a steady tension of 20 to 76 kN m-2 and stretches or releases of 0.02 to 0.6 mm applied in pairs, with the initial change reversed several hundred milliseconds later. Single stretches resulted in heat absorption and releases in heat production by the preparation. Net heat production resulted from complete cycles of length changes larger than 0.1 mm, whether the initial change was a stretch or a release. The heat produced by the complete cycle was attributed to the movement of the muscles over the thermopile. It was proportional to the difference in tension between the tibial and pelvic ends of the preparation and increased with the size and speed of the length change. Half the heat produced by a complete cycle of length changes was subtracted from the thermal response recorded in the first half-cycle to obtain the reversible component of the response. The reversible component was linearly related to the tension change for all sizes and speeds of length change which were studied, with the heat:tension ratio ranging from -0.0093 to -0.0179 in eleven muscles (mean -0.0128 +/- 0.0009). The constancy of the heat:tension ratio in rigor muscles over a wide range of mechanical conditions indicates that the source of the thermal changes is the normal elasticity of the preparation. Since the size of the ratio is approximately the same as that measured in active muscles, the tension-dependent component of the thermal response to length changes applied to active muscles is probably also of elastic origin.

Animals↗
PubMed1986

Influence of partial activation on force-velocity properties of frog skinned muscle fibers in millimolar magnesium ion.

Segments of briefly glycerinated muscle fibers from Rana pipiens were activated rapidly by a brief exposure to 2.5 mM free calcium followed by a solution containing calcium buffered with EGTA to produce the desired level of force. Steps to isotonic loads were made using a servomotor, usually 3-5 s after the onset of activation. The relative isotonic forces (P/P0) and velocities from contractions obtained under similar circumstances were grouped together and fitted with hyperbolic functions. Under the condition of 6 mM MgCl2 and 5 mM ATP, there was no significant difference in the relative force-velocity relations obtained at full activation compared with those obtained at partial activation when developed force was approximately 40% of its full value. Control experiments showed that a variety of factors did not alter either the relative force-velocity relations or the finding that partial activation did not change these properties. The factors investigated included the decline in force that occurs with each successive contraction of skinned fibers, the segment length (over a range of 1-3 mm), the sarcomere length (over a range of 1.9-2.2 microns), the magnesium ion concentration (26 microM and 1.4 mM were tested), the ATP concentration, the presence of free calcium, and the age of the preparation (up to 30 h). Attempts to repeat earlier experiments by others showing a dependence of shortening velocity on activation were unsuccessful because the low ionic strength used in those experiments caused the fibers to break after a few contractions. The main conclusion, that the shortening velocity is independent of the level of activation, is consistent with the hypothesis that the cross-bridges act independently and that activating calcium acts only as an all-or-none switch for individual cross-bridge attachment sites, and does not otherwise influence the kinetics of cross-bridge movement.

Adenosine Triphosphate↗
PubMed1986

Tension transients during the rise of tetanic tension in frog muscle fibres.

Tension transients were recorded from fibres isolated from the tibialis anterior muscle of the frog during the rise of tetanic tension at 0.8-2.5 degrees C. The length of a central segment of the fibre was controlled by feed-back from a spot-follower device. Length steps complete within 0.2 ms were applied at one end of the fibre, and tension changes were recorded at the other end with a transducer having a natural frequency of 10.8 kHz. The tension transients measured during the rise of force showed the four phases characteristic of transients recorded during the plateau of a tetanus and during shortening. The extreme tension change reached during a length change was smaller for a given size of step during the rise of tension than at the plateau, but by less than in proportion to the developed force, suggesting that stiffness increases earlier than tension. Stiffness changes were further assessed by matching the tension records from one fibre with the responses of an analogue circuit (delay line) representing the mechanical properties of the fibre and force transducer. Stiffness derived from these comparisons varied in approximately the same proportion as stiffness assessed from the extreme tension change. During the rise of tension, there was a roughly constant lag of tension behind stiffness, ranging from 11 to 16 ms in different fibres. Steps applied during the latent period showed a lag of about 10 ms from the first increase of stiffness to the first appearance of tension. The partial recovery of tension immediately following the step, phase 2, was faster at the low tension levels early in the tetanus. The intermediate level, T2, to which tension recovers during phase 2 scaled in approximate proportion to the tension level immediately preceding the step. This result is unlike the relative decrease in T2 levels we have recently described for steps applied during steady shortening, and suggests that the increased stiffness-tension ratio seen during the rise of tetanic force is not due to shortening within the sarcomeres. The results can be explained if the attachment of cross-bridges in the rising phase takes place in two steps, the initial state of attachment resulting in the production of little or no tension. Several such schemes are considered.

Animals↗
PubMed1985

Tension transients during steady shortening of frog muscle fibres.

Single intact fibres from frog muscle at 0-1 degrees C were stimulated to produce isometric tetani at a sarcomere length of about 2.25 micron, using a spot-follower apparatus to control the length of the central part of a fibre. When the plateau of the tetanus was reached the fibre was forced to shorten by applying a step and ramp length change in an approximation to an isotonic release. When tension had reached a steady level, Ti, during shortening, tension transients were elicited by applying step changes of length, complete within 0.2 ms, ranging from a stretch of 1.5 nm per half-sarcomere to a release of 6 nm per half-sarcomere. The tension transients recorded during shortening were qualitatively similar to those previously recorded in isometric tetani. There were four phases: phase 1, the change of tension during the step; phase 2, a rapid partial recovery of tension; phase 3, a delay or reversal of recovery; phase 4, a slower recovery of tension to the level before the step was applied. Measurements were made of the extreme tension, T1, attained during a step, and the level, T2, to which tension recovers in phase 2. The excursion of tension, [T1-Ti], during a small step of given size, fell with increase of shortening velocity, reaching about 40% of the isometric value near the maximum velocity of shortening. T2 fell as shortening velocity was increased and the fraction of steady tension recovered, T2/Ti, also decreased, so that the proportion of tension recovery in phase 4 increased. All the recovery phases became progressively more rapid with increase of shortening velocity. The early tension response was matched with a delay-line simulator so as to estimate the value of the instantaneous stiffness. Stiffness during shortening was found to decrease approximately linearly with tension, reaching about 35% of the isometric value as tension approached zero. It was impossible to match the early tension response in a rapidly shortening fibre without assuming decreased stiffness. The decline of stiffness is interpreted as due largely to reduced number of attached cross-bridges, but quantitative estimates would be affected by possible filament compliance and non-linearity of cross-bridge stiffness. The decrease in T2 also suggests fewer cross-bridges are attached as shortening velocity increases, but uncertainties about the processes determining phase 2 during shortening do not permit a precise estimate of stiffness to be made.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

System for automatic activation of skinned muscle fibers.

A system is described for automatically changing the solutions surrounding skinned muscle fibers at a controlled temperature. The system consists of a complex muscle chamber and solenoid valve-controlled vacuum-driven syringe pumps. The chamber has a muscle trough, a conduit for circulating coolant, and channels for precooling solutions. After traveling through the cooling channels, the solutions are injected into one end of the muscle trough and removed by suction at the other. The volume of the trough (approximately 40 microliter) is kept as low as possible to minimize the amount of solution required for complete solution exchange (approximately 400 microliter). Solution changes are complete within 400 ms. The timing of the sequence of solution changes is precisely controlled by digital timers that activate the solenoid valves of the pumps. By exposing the fibers briefly to a high concentration of free calcium and then changing to a buffered calcium solution, it is possible to achieve steady tension levels in 1-2 s, even when partially activating the fibers. Such rapid partial activation is possible because the exposure to free calcium can be precisely timed. The timers also allow the solution changes to be synchronized with other perturbations.

Animals↗
PubMed1984

Some consequences of body size.

The question of the proper size denominator for metabolic indices is addressed. Metabolic rate among different species is proportional to the 3/4 power of body weight, not surface area. Muscle power also varies with the 3/4 power of weight, suggesting that metabolic rate is determined mainly by muscle power. Power-to-weight ratio, specific metabolic rate, and a number of metabolic periods, including heart rate, all vary inversely with the 1/4 power of body weight. Thus the relative times required for physiological and pathological processes in different species may be estimated from the average resting heart rate for the species. There are not many small humans among athletic record holders in events involving acceleration and hill climbing, as would be expected if they had higher power-to-weight ratios. Thus the relationship between size and metabolic rate in different species should not be applied within the single species of humans. Evidence is reviewed showing that basal metabolic rate in humans is determined mainly by lean body mass.

Animals↗
PubMed1983

Relationship between sarcoplasmic reticulum volume and calcium capacity in skinned frog skeletal muscle fibres.

Semitendinosus fibres from Rana pipiens were examined in the electron microscope. When the aqueous solutions in which the fibres were prepared contained no sucrose, the sarcoplasmic reticulum was markedly swollen and possibly fragmented. When as little as 50 mM sucrose was included in the aqueous solution, the sarcoplasmic reticulum retained the flattened appearance characteristic of intact fibres. The degree of flattening was not substantially different with concentrations of sucrose ranging from 50 to 300 mM, suggesting that the flattened volume may be determined by structural elements. In all the fibre segments, the regularity of the hexagonal filament lattice was disrupted and the disruption was not affected by sucrose. Radioactive calcium uptake was measured in the presence and absence of 200 mM sucrose. The capacity of the sarcoplasmic reticulum (SR) was depressed by about 30% by the sucrose but the initial uptake was not significantly affected. This finding suggests that most of the calcium within the SR is bound and not free in solution.

Animals↗