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Biomedical subjects

L A Mulieri

Publications and source records attributed to L A Mulieri.

At least 55 records · Page 3Linked to original sources
PubMed1986

Myothermal economy of rat myocardium, chronic adaptation versus acute inotropism.

By means of rapid planar Hill type antimony-bismuth thermophiles the initial heat liberated by papillary muscles was measured synchronously with developed tension for control (C), pressure-overload (GOP), and hypothyrotic (PTU) rat myocardium (chronic experiments) and after application of 10(-6) M isoproterenol or 200 10(-6) M UDCG-115. Economy of force production was analyzed by the ratio of initial heat versus developed tension-time integral. This ratio was found to be reduced by 34% in GOP and by 43% in PTU myocardium (P less than 0.01, respectively) indicating increased economy of force production. In contrast, isoproterenol increased initial heat versus tension-time integral by 70% (P less than 0.01) indicating reduced economy of force production. No change in this ratio was found for UDCG-115. The presented data indicates that long and short term modulation of myocardial energetic costs of force generation is possible. The basic mechanisms for these myocardial alterations are discussed.

Animals↗
PubMed1986

Functional consequences of altered cardiac myosin isoenzymes.

This is a review of work dealing with the contribution of myocardial myosin isoenzymes to the performance of the heart muscle. Isoenzyme composition is altered in rabbit hearts by banding the pulmonary artery (increase in %V3) and thyroid hormone injection (increase in V1). Both treatments result in myocardial hypertrophy. The performance of the hearts rich in V3 or V1 myosin isoenzyme is assessed by simultaneous analysis of the myothermal and mechanical output of papillary muscles isolated from the right ventricle. Initial and tension dependent heart per tension time integral are decreased in the pressure overload and increased in the thyrotoxic hypertrophied hearts. Thus, the economy of isometric contraction is high in the hearts with the V3 myosin and low in the hearts with the V1 myosin. This change in performance is explained in terms of alterations in the cycling frequency and tension time integral of the myosin cross-bridge. In the pressure overload hearts the cross-bridge cycling frequency is decreased, while the tension time integral is increased. Conversely, in the thyrotoxic preparations the cycling frequency is increased and the tension time integral is decreased.

Adenosine Triphosphatases↗
PubMed1986

Determinants of energy utilization in the activated myocardium.

This is a review of work dealing with the effect of pressure overload and thryotoxic hypertrophy of rabbit hearts on the production of total activity related (TA) and initial (I) heats during isometric contraction. Pressure overload hypertrophy is produced by constricting the pulmonary artery with a spiral monel metal clip. Thyrotoxic hypertrophy is produced by 14 daily i.m. injections of 0.2 mg L-thyroxine per kilogram. Heat output is measured with Hill-type planar vacuum deposited bismuth and antimony thermopiles, and force is measured with a capacitance strain gauge. The pressure overload results in a depressed velocity of unloaded shortening, a depressed rate of isometric force development, and an increased time-to-peak tension. These changes are associated with a decreased myosin ATPase, a heart with no V1 myosin isoenzyme, and an increase in the economy of isometric force development (integral of Pdt/TA, integral of Pdt/I). The thyrotoxic hearts exhibit an increased velocity of shortening and rate of force development, and a decrease in time-to-peak tension. These changes are associated with an increase in myosin ATPase activity, a heart with increase in the V1 isoenzyme composition (88% V1), and a decrease in the economy of isometric force development (integral of Pdt/TA, integral of Pdt/I). The changes in the two types of hypertrophied hearts are interpreted in terms of altered cross-bridge cycling rates and changes in cross-bridge tension time integral as well as excitation contraction coupling phenomena. In the thyrotoxic hearts there is an increase in the economy of the recovery processes. Both types of hypertrophy are considered to be adaptive and involve the coordinated restructuring of the excitation-contraction, contractile, and recovery systems.

Animals↗
PubMed1985

The economy of isometric force development, myosin isoenzyme pattern and myofibrillar ATPase activity in normal and hypothyroid rat myocardium.

Hypothyroidism was induced in Wistar-Kyoto rats by adding propylthiouracil to the drinking water (0.8 mg/ml). Initial heat, total activity-related heat, and resting heat rate were measured in left ventricular papillary muscle preparations of propylthiouracil-treated and control rats contracting isometrically at 12 beats/min (21 degrees C), using Hill type, planar vacuum-deposited bismuth and antimony thermopiles. In the propylthiouracil preparations, relative to control, time-to-peak tension increased from 288 +/- 27 (mean +/- SD) to 411 +/- 25 msec (P less than 0.001), dp/dtmax decreased from 38.3 +/- 9.5 to 20.4 +/- 3.5 g X mm-2/sec (P less than 0.001), and peak developed tension decreased from 6.11 +/- 1.75 to 4.64 +/- 0.89 g X mm-2 (P less than 0.05). In the propylthiouracil preparations, initial heat was significantly (P less than 0.001) reduced by 27 or 43% when normalized to peak twitch tension or tension-time integral, respectively. In experiments where the papillary muscles were tetanized, the slope of the linear function of total activity-related heat versus tension-time integral was decreased by 43% (P less than 0.001) in the propylthiouracil preparations, indicating an improved economy of isometric tension maintenance. The predominant myosin isoenzyme of the left ventricular wall, as well as the papillary muscle myocardium, was the V3 variety in the propylthiouracil animals, in contrast to V1 in the controls. Myofibrillar actomyosin calcium-magnesium-stimulated adenosine triphosphatase activity was significantly (P less than 0.02) decreased from 55 +/- 18 (control) to 31 +/- 8 nmol inorganic phosphate ion/mg X min (propylthiouracil).(ABSTRACT TRUNCATED AT 250 WORDS)

Actomyosin↗
PubMed1984

The ultrastructure of myocardial hypertrophy: why does the compensated heart fail?

Several qualitative features of the ultrastructure of pressure overload and thyrotoxic myocardium are unique markers of the type and quantity of increased work the heart has been required to perform. Furthermore, they are reminiscent of features of normally growing myocytes, implying that the changes in the hypertrophied cell are the consequence of normally present capacities for adaptation to a demand for increased myocardial work. Thyrotoxic myocardium has two features which distinguish it from normal and pressure overloaded hearts: the mitochondria are large and have a peculiar fragile or lacey appearance. Many myocytes show considerable disorganization of sarcomeric myofilaments. Pressure overloaded hearts have smaller and more numerous mitochondria than the normal myocyte. Their sarcomeres have thicker Z bands than controls. Double intercalated discs are also a feature of these myocytes. Several features of hypertrophied myocytes are seen in both types of hypertrophy: RER and ribosomes on the external nuclear membrane. There are polyribosomes aligned along the long axes of thick filaments, presumably involved in myosin synthesis or transformation within the cell. There are areas of sarcomerogenesis both under the sarcolemma and within the cell at the intercalated disc. These are characterized by fragments of myofilaments, polyribosomes and rough endoplasmic reticulum. Quantitatively, myocyte composition is transiently disturbed but, like that of normally growing hearts, returns to control values as the adaptation to stress is negotiated.

Adaptation, Physiological↗
PubMed1984

A myothermal analysis of the myosin crossbridge cycling rate during isometric tetanus in normal and hypothyroid rat hearts.

Hypertrophied rabbit heart papillary muscles (thyrotoxicosis), with a high V1/V3 myosin isoenzyme ratio and contractile protein ATPase activity, have a high velocity of unloaded shortening and a decrease in the myothermal economy of isometric twitch force development and dissipation; in hypertrophied hearts (pressure overload) with a low V1/V3 isoenzyme ratio and ATPase activity, the converse was found to be true (Am J Cardiol 1979; 44:947-953; Fed Proc 1982; 41:192-198). In the present study the confounding problem of internal shortening, which takes place during force development and dissipation in the isometric twitch, is minimized by carrying out measurements of the rate of heat liberation during the plateau phase of tetanic force maintenance. The studies are further extended to another species (rat) where the V1/V3 myosin isoenzyme ratio is altered by treating the animal with propyl thiouracil added to the drinking water (PTU); here the contractile protein alteration occurs with myocardial atrophy rather than hypertrophy. High resolution, rapid temperature measurements are made in tetanically stimulated isometrically contracting rat heart papillary muscles from normal (high V1/V3 ratio) and PTU treated (low V1/V3 ratio) rats to assess the relationship between contractile protein performance (crossbridge cycling rate) in the intact muscle and that under controlled conditions in isolated myofibrils. In papillary muscles from the normal heart the crossbridge cycling rate (+/- SEM) during force maintenance was 6.53 (+/- 1.73) cycles/second compared with 3.13 (+/- 0.24) and 0.53 (+/- 0.17) cycles s-1 in the myofibril at high and low ionic strength, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1982

Activation heat and latency relaxation in relation to calcium movement in skeletal and cardiac muscle.

Measurements of activation heat, initial heat, twitch tension, and latency relaxation were made using thin-layer, vacuum-deposited thermopiles and isometric force transducers, respectively. Experiments were performed on frog skeletal muscle fiber bundles and on rabbit right ventricular papillary muscles at 0, 15, ans 21 degrees C in normal and 1.75X to 2.5X mannitol hyperosmotic bathing solutions. In skeletal muscle, activation heat, obtained by stretching to zero overlap, was only slightly affected by 1.75X hyperosmotic solution and consisted of a fast and a slow component. Both components have a refractory period and a relatively refractory period which can be demonstrated by double pulse stimulation. The twitch potentiators Zn2+ and caffeine increase the total activation heat and the magnitude and rate of the fast component. The temporal relation between the latency relaxation and activation heat is demonstrated. The latency relaxation is independent of the number of sarcomeres in series in a muscle. Activation heat and latency relaxation records from heart muscle are obtained in 2.5X hyperosmotic bathing solution. A model of excitation--contraction coupling is presented which indicates that (1) the downstroke of the latency relaxation monitors the functioning of the Ca2+-permeability or debinding mechanism in the terminal cisternae, (2) the fast component of activation heat monitors the amount of Ca2+ bound to troponin C, and (3) the total amplitude of activation heat is a measure of the total quantity of Ca2+ cycled in a twitch.

Action Potentials↗
PubMed1982

Heat production during hypoxic contracture of rat myocardium.

Contracture due to hypoxia, to both oxygen and glucose deficiency, and to potassium chloride was induced in rat left ventricular papillary muscle preparations. Under contracture conditions, the sum of resting heat plus contracture heat was measured using Hill-type, planar vacuum-deposited thermopiles. On the basis of the measured total and initial heat output and the corresponding tension-time integral during single twitches under control conditions (Lmax, 21 degrees C, stimulus frequency 12/min), the expected heat output during contracture was calculated, assuming that the contracture tension is maintained by the same calcium-induced cross-bridge cycling as occurs in the single twitch response. With potassium chloride, the contracture tension was 1.33 +/- 0.27 g/mm2, a value which is similar to those found in hypoxic contracture and in contracture due to both oxygen and glucose deficiency. There was no significant difference between measured and calculated values for resting heat plus contracture heat (8.40 +/- 2.84 mW/g measured, 8.55 +/- 2.50 mW/g calculated); there was a linear correlation (r = 0.99) between predicted and measured values (P less than 0.05). The measured value for resting plus contracture heat in hypoxic contracture was 1.88 +/- 0.37 mW/g, whereas a value of 4.80 +/- 1.09 mW/g (P less than 0.005) was calculated on the basis of the twitch heat per tension-time integral and contracture tension (1.09 +/- 0.31 g/mm2). Contracture tension was 1.80 +/- 0.78 g/mm2 in contracture due to oxygen and glucose deficiency, whereas the value for resting plus contracture eat was 1.61 +/- 0.56 mW/g. The calculated resting plus contracture heat value for this preparation was significantly higher (7.45 +/- 3.75 mW/g; P less than 0.05). There was no significant regression between predicted and measured resting heat plus contracture heat in the hypoxic contracture preparations (slope not different from zero). In contracture due to oxygen and glucose deficiency, the linear regression had a slope of 6.06 (P less than 0.05). The results suggest that the potassium chloride contracture relies on cross-bridge cycling as in a twitch contraction, whereas hypoxic contracture and that due to oxygen and glucose deficiency may be explained by cross-bridge formations with no, or very low, heat production, i.e., contracture tensions due to hypoxia and to oxygen and glucose deficiency are maintained by rigor-like cross-bridge formation or by slowly cycling cross-bridges with a long time of cross-bridge attachment.

Animals↗
PubMed1982

Myocardial adaptation to stress from the viewpoint of evolution and development.

Myocardial hypertrophy, which results from the increase in demand placed on the heart, does not involve the simple enlargement of the myocardial cell. Instead, the cells are restructured in a manner that depends on the nature of the stress applied. The cellular reorganization involves the contractile, EC coupling, and recovery systems. In the remodeling of each of these systems, a repertoire of functional adaptation is used which bears a remarkable similarity to the changes seen in the differentiation of species and the development of muscle type. Thus, in pressure overload hypertrophy, where the maintenance of persistent high pressure in a necessity, the contractile system of the muscle is slower and more economical. This is similar to the specialization seen in the tortoise or in slow muscles like the rat soleus. In thyrotoxic hypertrophy, where the demand is to move the blood at high velocity, the muscle is fast and less economical. This is similar to the specialization seen in the frog sartorius or rat EDL. The restructuring involves specific molecular changes that uniquely adapt the muscles for the tasks at hand.

Adaptation, Physiological↗
PubMed1982

Heat, mechanics, and myosin ATPase in normal and hypertrophied heart muscle.

In this paper we review our previous work on the myothermic economy of isometric force production in compensated cardiac hypertrophy secondary to pulmonary artery constriction (pressure overload) and/or thyrotoxicosis (volume overload). Hypertrophy-induced changes in isotonic and isometric twitch mechanics are correlated with accompanying changes in actin-activated myosin ATPase and heat liberation. Heat measurements were made with rapid, high-sensitivity thermopiles on right ventricular papillary muscles from normal and hypertrophied rabbit hearts. Total activity-related heat was separated into initial and recovery heat. Initial heat was separated into a tension-dependent component (TDH) relating to cross-bridge activity, and a tension-independent component (TIH) relating to excitation-contraction coupling. There were oppositely directed changes in most parameters studied in pressure overload hypertrophy (P) as compared with thyrotoxic hypertrophy (T). Thus, in P there was depression (30-50% in the rate of isometric force production, mechanical Vmax, TDH and TDH rate, myosin ATPase, TIH, and prolongation in time-to-peak twitch tension, whereas in T all parameters were oppositely changed except for no change in TIH. Thyrotoxicosis following pressure overload reversed the P-induced changes in all parameters. There was a direct, linear relation between in vitro actin-activated myosin ATPase and in vivo TDH. However, TDH per unit twitch tension or tension-time integral varied inversely with ATPase, making force production more economical than normal in P muscles and less economical than normal in T muscles. These cellular changes beneficially equip P hearts for slow, high-pressure, economical pumping the T hearts for fast, high-volume, uneconomical pumping. The differences are similar to those between slow and fast skeletal muscle and between neonatal and adult skeletal muscle. The mechanism of these changes is discussed in terms of an enzyme kinetic scheme of chemomechanical coupling in actomyosin interaction.

Actins↗
PubMed1979

Heart muscle mechanics.

The goal implicit in the research reviewed above is to describe the contractile behavior of heart muscle in terms of crossbridge and filament behavior. It is necessary to elucidate these details in cardiac muscle because of the distinct biochemical differences between skeletal and cardiac myosin. As is evident in this review, significant advances have been made toward describing unique mechanical properties of cardiac muscle crossbridges. Several major problems now require attention: (a) Activation parameters are labile, making mechanical measurements sensitive to measurement perturbation; (b) significant structural inhomogeneities at the cellular and sarcomere level prevent precise assignment of externally measured force to internal structures (force generators, passive elements) within whole cardiac muscle and individual cells; (c) high resting stiffness and forces of poorly understood origin and properties confound attempts to interpret force measurements and dynamics. The differences between heart and skeletal muscle myosin may provide the means for identifying structural counterparts of the Huxley-Simmons model (33); they may also be useful in evaluating the electrostatic and quantum-mechanical models.

Adenosine Triphosphatases↗
PubMed1977

Metal-film thermopiles for use with rabbit right ventricular papillary muscles.

A method of fabricating Hill-Downing type, planar thermopiles by vacuum-deposition techniques is described in detail. The present model was designed for initial heat measurements on rabbit papillary muscles as small as 1 mg blotted wt, but it is also suitable for small bundles of frog muscle fibers (30-75). The thermopile has 20 or 14 junctions, an active length of 5 or 3.5 mm, and an actual thickness of 20 micrometer. It has an effective heat capacity of about 0.3 mcal/degrees C, a heat loss coefficient of about 0.3 mcal/degrees C - s, a temperature sensitivity of 1.4 mV/degrees C (20 junctions), and an electrical resistance of 180-200 omega. Infrared-emitting diodes are used to heat the thermopile and muscle artificially for thermal time constant and conduction-delay measurements. Performance of the thermopiles is demonstrated with initial heat records from rabbit right ventricular papillary muscles and a bundle of frog semitendinosus muscle fibers. Results of preliminary experiments concerning latency for heat generation, initial rate of heat generation, and activation heat in both types of muscles are presented.

Alloys↗
PubMed1976

Non-hyperbolic force-velocity relationship in single muscle fibres.

The force-velocity relation has been studied in sixteen single fibres from frog semitendinosus muscle with particular attention to the high-force portion of the curve. The force-velocity curve was hyperbolic except for a reversal of curvature near 80% measured isometric tension (PO). Rectangular hyperbolas fitted (linear, least-squares method) these data well only when values below 0.78 PO were considered. Extrapolation of these hyperbolas above 0.78 PO gave predicted isometric tensions (P*O) which averaged 32+/-6% above the measured PO values. Hill's constants (1.84 degrees C) for these hyperbolas were: a/P*O=0.177+/-0.021, b=0.329+/- 0.035 M.L./sec, Vmax=1.91+/-0.074 M.L./sec. The reversal of curvature persisted when force-velocity data were obtained using: 1 or 60 min response intervals, afterloaded isotonic responses, grid stimulation, electrically induced contractures and bundles of fibres. The reversal of curvature diminished when force-velocity data were obtained from slightly stretched fibres (about 2.3 mum sarcomere length as compared to 2.1 mum in the control). The results indicate that sarcomere length redistributions probably do not account for the non-hyperbolic force-velocity relation. An explanation for the behavior based on the geometry of the contractile filament lattice is discussed.

Animals↗
PubMed1972

The dependence of the latency relaxation on sarcomere length and other characteristics of isolated muscle fibres.

1. The latency relaxation has been examined in single fibres from frog striated muscle with particular attention given to its possible relation to Ca(2+) release during excitation-contraction coupling.2. Latency relaxations were recorded at 19-23 degrees C from massively stimulated (0.2 msec pulses) single fibres using two selected RCA 5734 transducer tubes in a bridge circuit.3. The depth of the latency relaxation has its full value when stimulus strength is between 40 and 400% above twitch threshold. Stronger stimuli reversibly diminish the latency relaxation.4. The variation in depth of latency relaxation with sarcomere length was found similar to that reported previously for multifibre preparations but in single fibres the peak of the curve consists of a plateau between sarcomere lengths of 2.8 mu and 3.2 mu.5. Sucrose hypertonicity increases the depth of the latency relaxation at sarcomere lengths below 2.8 mu but above this length it has either no effect or a depressant effect depending on the degree of hypertonicity.6. The maximal depth of the latency relaxation (measured at 3 mu) averaged 0.23% of the maximal tetanus tension (measured at 2.2 mu) and was strongly correlated (r = 0.87) with the latter in forty-five single fibres.7. The maximal depth of the latency relaxation is not correlated with the number of sarcomeres in series in a fibre.8. The results of this study are shown to fully support and extend Sandow's (1966) hypothesis that the latency relaxation is caused by release of activator Ca(2+) from the sarcoplasmic reticulum.

Animals↗
PubMedDate not supplied

The partitioning of altered mechanics in hypertrophied heart muscle between the sarcoplasmic reticulum and the contractile apparatus by means of myothermal measurements.

Cardiac hypertrophy in the rabbit, secondary to pulmonary artery stenosis, results in a decrease in unloaded shortening velocity (Vmax) and maximum rate of isometric force development (dP/dtmax), while the peak isometric twitch tension is unchanged and time to peak tension (TPT) is increased. The principle hypothesis used to explain these results involve 1) slowing of myosin cross bridge movement as reflected in depressed myosin ATPase activity and 2) changes in excitation contraction coupling phenomena resulting in changes in intracellular Ca++ movement. Ca++ and actin activated myosin ATPase from the hypertrophied (H) muscles is depressed by 30%. Total initial heat, tension dependent heat and tension independent heat are depressed in H muscles by 57, 56, and 61% respectively. The rate of tension independent heat production in H preparations is depressed by 66%. From these data it is concluded that 61% of the depression in Vmax could be accounted for by the alteration in myosin with the reminder attributable to changes in EC coupling. Increased TPT can be accounted for by the change in rate of Ca++ flux as indicated by the alterated rate of tension independent heat evolution.

Adenosine Triphosphatases↗
PubMedDate not supplied

Energetic changes of myocardium as an adaptation to chronic hemodynamic overload and thyroid gland activity.

Pressure-overload cardiac hypertrophy and hypothyroidism were shown to be associated with a decreased maximum shortening velocity of the myocardium. To investigate the nature of these intrinsic myocardial changes, we studied the energetic consequences in left ventricular papillary muscles of the rat by using standard HILL planar vacuum-deposited antimony-bismuth thermopiles. To evaluate the economy of isometric force generation and maintenance, we analyzed the ratio of liberated heat and developed tension or developed tension-time integral in twitches and experimentally induced tetanic contractions. Hypothyroidism was induced by treatment with propylthiouracil (PTU), and hypertension by operative narrowing of the left renal artery of rats according to Goldblatt (GOP). In the myocardium of hypothyroid as well as hypertensive rats, initial heat per peak twitch tension and total activity-related heat per tension-time integral were significantly reduced compared to controls. In tetanic contractions, total activity-related heat per tension-time integral was also decreased in PTU and GOP myocardium when compared to controls. Thus, the economy of force generation and maintenance is improved in the myocardium of the experimental animals. The data is interpreted in terms of altered cross-bridge cycling rates which are shown to be associated with changes in the myosin isoenzyme pattern. The intrinsic changes of the myocardium due to pressure-overload hypertrophy and hypothyroidism are considered to be adaptive rather than pathologic reactions of the myocardium.

Adaptation, Physiological↗