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Biomedical subjects

L E Ford

Publications and source records attributed to L E Ford.

At least 55 records · Page 3Linked to original sources

Dimensional correlates of left ventricular dilation in the presence of hypertrophy.

Twelve normal subjects, 50 patients with valvular heart disease, and 14 with hypertension were studied. Those with valvular disease were divided into two groups: 28 with angiographically measured ejection fractions greater than or equal to 0.6 and 22 with ejection fractions less than 0.6. The echocardiographically measured ventricular thickness divided by radius ratio (t/r) was approximately proportional to peak systolic pressure (P) in all groups having ejection fractions greater than or equal to 0.6, so that the t/r divided by P ratios were nearly the same. Patients with ejection fractions less than 0.6 had significantly lower t/r divided by P values. No single component of the t/r divided by P ratio would identify the patients with lower ejection fractions. The t/r divided by P ratios in 14 hypertensive patients were nearly identical to the ratios in six patients with aortic stenosis and ejection fractions greater than or equal to 0.6, indicating that an aortic valve gradient does not cause a grossly abnormal form of pressure hypertrophy. The t/r ratio is thus a double sensitive, noninvasive index of dilation when correlated with systolic pressure.

Adult↗

Internal viscoelastic loading in cat papillary muscle.

The passive mechanical properties of myocardium were defined by measuring force responses to rapid length ramps applied to unstimulated cat papillary muscles. The immediate force changes following these ramps recovered partially to their initial value, suggesting a series combination of viscous element and spring. Because the stretched muscle can bear force at rest, the viscous element must be in parallel with an additional spring. The instantaneous extension-force curves measured at different lengths were nonlinear, and could be made to superimpose by a simple horizontal shift. This finding suggests that the same spring was being measured at each length, and that this spring was in series with both the viscous element and its parallel spring (Voigt configuration), so that the parallel spring is held nearly rigid by the viscous element during rapid steps. The series spring in the passive muscle could account for most of the series elastic recoil in the active muscle, suggesting that the same spring is in series with both the contractile elements and the viscous element. It is postulated that the viscous element might be coupled to the contractile elements by a compliance, so that the load imposed on the contractile elements by the passive structures is viscoelastic rather than purely viscous. Such a viscoelastic load would give the muscle a length-independent, early diastolic restoring force. The possibility is discussed that the length-independent restoring force would allow some of the energy liberated during active shortening to be stored and released during relaxation.

Animals↗

Velocity transients and viscoelastic resistance to active shortening in cat papillary muscle.

When isotonic force steps were applied to activated papillary muscles, the velocity was almost never constant. Early rapid shortening associated with the step persisted for 2-7 ms after the step ends. The early rapid shortening is attributed to lightly damped series elastic recoil and velocity transients of the contractile elements. In most steps, the subsequent velocity declines progressively with shortening, and most of the decline in velocity can be accounted for by compression of a viscoelastic element in parallel with the contractile elements. To demonstrate this, the time course of isotonic velocity was compared with a model in which the force-velocity characteristics of the contractile element were assumed to be constant, and the decline in velocity was due to increasing compression of the viscoelastic element. This model predicted the observed results except that the predicted velocities rose progressively above the measured values for steps to light loads applied late in the twitch, and fell below the velocity trace for heavy loads applied early in the twitch. These deviations would occur if rapid shortening caused deactivation late in the twitch, and if activation were rising early in the twitch. A conditioning step applied to the muscle during the rise of force depressed both isometric force and maximum velocity measured at the peak of force; isometric force was more depressed with later conditioning steps than with earlier steps, while maximum velocity was depressed by about the same extent with both early and late steps. This difference between the effects on isometric force and maximum velocity are explained by a combination of deactivation and viscoelastic load.

Animals↗

A sensitive photoelectric force transducer with a resonant frequency of 6 kHz.

A displacement-type photoelectric force transducer with a projection arm and a resonant frequency of 6 kHz is described. A vane on a moving element partially interrupts a light beam shining on a pair of phototransistors. Movement of the vane causes changes in the phototransistor currents, which are amplified to give an overall sensitivity of 10 mV/mg. Most of the half of each phototransistor not under the vane is covered by a mask, the edge of which is parallel to the edge of the vane. This increases the sensitivity of the transducer so that stiffer moving elements can be used. Compliance of the transducer at the tip of the projection arm is about 10 micrometers/g. The inertia of the lightweight moving element is minimized by having it rotate about a twisting strip hinge. The equivalent mass of the moving element at the tip, 6 mm from the pivot, is about 0.9 mg. The principal advantages of the transducer over other types is that it is nearly impervious to moisture.

Animals↗

The relation between stiffness and filament overlap in stimulated frog muscle fibres.

1. Tension transients were recorded at sarcomere lengths from 2.0 to 3.2 mum in isolated fibres from the tibialis anterior muscle of frogs during tetanic stimulation at 0-1 degrees C. 2. The length of a selected portion of the fibre was controlled by feed-back from a spot-follower device. The step was complete in 0.2 ms and the natural frequency of the force transducer was 10.8 kHz. 3. The transients were analysed by comparing the tension record with the output of an analogue circuit (delay line) which contained components representing (a) force transducer response, (b) fibre inertia, (c) viscosity and inertia of surrounding fluid, (d) passive stiffness and viscosity of the fibre, (e) tendon compliance and (f) stiffness and early tension recovery of the contractile apparatus. 4. In releases at different sarcomere lengths, the instantaneous stiffness and the early tension recovery attributed to the contractile apparatus varied almost exactly in proportion to the developed tension. In the later phases of the transient there were minor deviations from proportionality. 5. The results confirm that the entire transient represents events in the cross-bridges. 6. At full overlap, the compliance attributable to the cross-bridges is at least 80%, and probably well over 90% of the measured instantaneous compliance of the fibre. Stiffness can therefore be used as a measure of the number of attached cross-bridges. 7. The amount of instantaneous sliding movement of thick relative to thin filaments required to bring tension in a cross-bridge from the isometric value to zero is about 3.9 nm if filament and Z-line compliance are negligible, as suggested by the results. It is not however excluded that filament compliance, though small, may be sufficient to reduce this figure to 3.5 nm or possibly 3.1 nm. 8. The responses to quick stretch, unlike those to release, could not be satisfactorily matched with the delay line. The deviations suggest that the instantaneous elasticity is non-linear in stretches. 9. In resting fibres at all sarcomere lengths, the first peak of the tension response was determined chiefly by fibre inertia and viscosity, rather than elasticity.

Animals↗

Effect of myocardial shortening velocity on duration of electrical and mechanical systole. S2T interval as measure of shortening rate.

To determine the effect of myocardial shortening velocity on the duration of electrical and mechanical systole, five healthy men, ages 32 to 41, were studied. Carotid message and atropine were used to define the effects of changes in heart rate without changes in shortening rate. The effects of amyl nitrite, which produced approximately the same degree of tachycardia as atropine but a significantly higher maximum shortening rate, were compared with those of atropine to assess the effects of faster shortening velocities. The increased heart rate produced by both agents caused a substantial decrease in both the QT and the S1S2 intervals, but the QT interval was longer and the S1S2 interval shorter with the amyl nitrite. Thus, the S2T interval was substantially longer after amyl nitrite. The results are in keeping with the finding in isolated cardiac muscle that active shortening increases action potential duration and decreases the duration of mechanical activation. These observations raise the possibility that longer QT intervals and shorter S1S2 intervals would also be seen in patients with hypokinetic ventricular segments when the healthy muscle contracts more vigorously to compensate for the weaker segments.

Adult↗

The angiographic effect of ergonovine and nifedipine in coronary artery spasm.

In a patient with variant angina, we have shown that the calcium-channel blocker nifedipine inhibits both spontaneous and ergonivine-induced coronary artery spasm. It had no effect, however, on the dose-related diffuse vasoconstriction caused by ergonovine, suggesting two distinct responses of coronary arteries to ergonovine provocation. Nifedipine did not cause epicardial coronary artery dilatation, as did nitroglycerin, supporting the rationale of using both therapies together to treat coronary artery spasm.

Adult↗

Effect of afterload reduction on myocardial energetics.

Consideration of muscle energetics suggests that the ventricle has a very definite optimum range of operating wall tensions, and that clinical advantage can be gained by maintaining the tension within this range.

Energy Metabolism↗

Rheumatoid-like arthritis associated with a colonic carcinoma.

A 76-year-old woman with rapidly progressive athritis associated with a rising rheumatoid factor, acute joint effusion, and fever had remission of her symptoms and return of her laboratory values to normal following removal of a colonic carcinoma.

Aged↗

A piezoelectric force transducer for single muscle cells.

A cantilevered piezoelectric force transducer is described. The cantilevered element has a 6-mm glass extension that can be projected into a horizontal muscle bath from above. By adjusting the length of the piezoelectric bar from 1 to 4 mm, the sensitivity of the device can be varied between 25 and 100 mV/mN (0.25--1.0 mV/mg) with its resonant frequency varying inversely between 8 and 15 kHz. Although moderately fragile, the sensing elements are inexpensive and easily made. The output of the sensing element is amplified by a small, unity-gain, high-input-resistance amplifier mounted on a support block with the element. Although the arrangement does not provide a DC output, its time constant of over 500 s is sufficiently long for measuring tension during muscle contractions lasting 1--2 s.

Muscle Contraction↗

Tension responses to sudden length change in stimulated frog muscle fibres near slack length.

1. Apparatus for applying a step change of length to an isolated muscle fibre is described. The step was complete in about 0.2 ms.2. Effects of tendon compliance were eliminated by using a spot-follower device and by gripping the tendons with metal clips close to the fibre ends.3. The natural frequency of the force transducer was above 10 kHz.4. Steps of various amplitudes and in either direction were applied to isolated muscle fibres about 6 mm long from the anterior tibial muscle of Rana temporaria during tetanic stimulation. Initial sarcomere length was 2.0-2.2 mum, and temperature was 0-3 degrees C.5. The tension response to a step could be divided into four phases. The initial response was an apparently elastic change during the step itself (phase 1). After the step was completed there was a rapid partial recovery towards the original tension (phase 2, lasting 2-5 ms), followed by a slowing or reversal of recovery (phase 3, 10-50 ms), and finally a much slower return to the original tension (phase 4). Most of this paper is concerned with phases 1 and 2.6. The initial tension change (phase 1) occurred synchronously with the applied length change, indicating that the fibres possess a compliance which is almost linear and almost undamped. Its stiffness is such that an instantaneous shortening of about 4 nm per half-sarcomere would bring the tension to zero from its isometric value.7. The absence of detectable damping during phase 1 indicates that the viscosity of a stimulated fibre is substantially less than the apparent viscosity of a fibre at rest.8. The instantaneous force-extension curve approached the length axis at a sharp angle and a negative tension appeared at the force transducer when a very large step was applied. These observations suggest that the structures responsible for the stiffness of the fibre remain rigid when they are not under tension.9. During the few milliseconds after the step (phase 2) the tension recovered part of the way toward the level which existed before the step. In shortening steps the time course of this recovery was adequately fitted by the sum of four exponential terms, and was similar in steps of different amplitude but with a time scale shorter the larger the step. In stretches the slow components were relatively larger than in releases.10. The tension level, T(2), approached during phase 2 depended only on the total amplitude of the step and not on the time course of the length change, provided it was complete in 1-2 ms. The extreme tension reached during a step could thus vary widely without detectable change in T(2).11. With stretches and releases of up to about 3 nm per half-sarcomere this early recovery was almost complete, so that the curve of T(2) against step amplitude was nearly horizontal. With larger releases the line curved downwards, reaching zero in a release of about 14 nm per half-sarcomere.12. When the temperature was raised both the developed tension and the stiffness increased, but the relative increase was greater for tension than for stiffness. The amount of instantaneous shortening needed to bring tension to zero was therefore also increased.13. A set of empirical equations is given which describe adequately the first few milliseconds of the tension change in response to any imposed time course of shortening.14. The rapid elasticity and early tension recovery resemble the response of a combination of two elastic components and one viscous component. Reasons are given for preferring an interpretation in terms of an undamped compliance in series with a damped compliance (Voigt element) rather than an undamped elasticity in parallel with a series combination of viscous and elastic components (Maxwell element).15. The rapid compliance does not correspond to the ;series elastic component' of two-component theories of muscle contraction.

Animals↗

Heart size.

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Animals↗

Calcium uptake and force development by skinned muscle fibres in EGTA buffered solutions.

1. The uptake of (45)Ca and the development of force by segments of skinned muscle fibres were measured in Ca solutions buffered with EGTA. When the Ca ion concentration in these solutions was above the contraction threshold, Ca was accumulated by the sarcoplasmic reticulum during the delay phase before force developed. The uptake rate increased, and the length of the delay decreased, when the concentration of the calcium buffer was increased.2. The maximum accumulation of Ca was 2-3 mM. Force developed, ending the delay phase, when the calcium uptake approached this maximum level.3. The pattern of force development suggested that this process was often accompanied by a sudden release of accumulated Ca.4. The relation between the kinetics of (45)Ca uptake and the interaction of calcium with EGTA and the sarcoplasmic reticulum is discussed. The data indicate that at the low concentrations necessary for relaxation the sarcoplasmic reticulum takes up Ca fast enough to account for the rate at which force falls when intact muscle fibres relax.

Acetates↗

Intracellular calcium movements in skinned muscle fibres.

1. Force development and (45)Ca movement between the internal membranes and the myofilament space were measured in segments of skinned muscle fibres.2. At 20 degrees C calcium ions in the myofilament space of calcium loaded fibres caused the internal membranes to release a substantial amount of calcium which produced a large force spike. Calcium produced a similar force spike in fibres containing only the physiological level of calcium when the temperature was lowered to about 6 degrees C.3. The force spike at 6 degrees C was inhibited when the magnesium concentration in the bathing solution was increased from 1 to 6 mM. The pattern of force development in preparations transferred directly from oil to a free calcium solution indicated that the normal concentration of Mg(2+) in the myofilament space of intact fibres is of the order of 10(-3)M.4. A possible role for the regenerative calcium release mechanism in the physiological activation of muscle fibres is suggested.

Action Potentials↗