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C L Gibbs

Publications and source records attributed to C L Gibbs.

At least 55 records · Page 3Linked to original sources

Activation heat in rabbit cardiac muscle.

1. Activation heat was estimated myothermically in right ventricular papillary muscles of rabbits using several different methods. 2. Gradual pre-shortening of muscles to a length (lmin) where no active force development took place upon stimulation led to relatively low estimates of activation heat (1.59 +/- 0.26-2.06 +/- 0.57 mJ g-1 blotted wet weight, mean +/- S.E.M., n = 10). 3. Quick releases applied during the latency period, before force development, from lmax to various muscle lengths allowed a heat-stress relation to be established. The zero-stress intercept of this relation estimated the activation heat to be 3.27 +/- 0.40 mJ g-1; this was close to the experimentally measured value of 3.46 +/- 0.39 mJ g-1 (mean +/- S.E.M., n = 23) found by quick release from lmax to lmin. 4. The magnitude of the activation heat measured by the quick-release technique is dependent upon the extracellular Ca2+ concentration and there is good correlation between activation heat magnitude and peak developed stress. 5. In agreement with expectations based on the aequorin data of Allen & Kurihara (1982) a prolonged period of time spent at a short length is shown to depress the subsequently determined activation heat. 6. Hyperosmotic solutions (2.5 x normal) only abolished active stress development at low stimulus rates (0.2 Hz) and the activation heat measured at lmax under these conditions was 2.03 +/- 0.12 mJ g-1 (mean +/- S.E.M., n = 6). This value was significantly lower than the latency release estimate of activation heat in the same preparations (2.93 +/- 0.39 mJ g-1). 7. The latency release method of estimating activation heat results in activation heat values that account for approximately 30% of total active energy flux per contraction; a fraction comparable to that found in skeletal muscle. Calculations based on the data suggest that, under our experimental conditions, total Ca2+ release per beat lies between 50 and 100 nmol g-1 wet weight which would produce less than half-maximal myofibrillar ATPase activity when allowance is made for the passive Ca2+-buffering capacity of the myocardial cell.

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Heat production of rat anococcygeus muscle during isometric contraction.

Heat production, unloaded shortening velocity (Vus), and load-bearing capacity (LBC) were studied in the isolated rat anococcygeus muscle during isometric contractions at 27 degrees C. The relation between the total suprabasal heat produced and the stress-time integral for isometric contractions of various durations was curvilinear, demonstrating a decreasing slope as contractile duration increased. The rate of heat production at 600 s was approximately 68% of the peak value of 6.55 mW/g that occurred at 10 s. At the same time, force rose from a mean of 92 mN/mm2 at 10 s to a value of 140 mN/mm2 at 600 s. This produced a nearly threefold increase in the economy of force maintenance. The decline in the rate of heat production was accompanied by a decline in Vus from 0.56 Lo/s at 10 s to 0.28 Lo/s at 600 s, where Lo is the length for optimal force development. This suggests the fall in the rate of heat production was caused, at least in part, by a slowing of cross-bridge kinetics. The ratio of LBC to developed tension at 10 s was not significantly different from the ratio at 600 s, suggesting that the increase in tension was due to an increased number of attached cross bridges. The decline in heat production, therefore, appears contradictory, since an increased number of attached cross bridges would predict an increased rate of energy expenditure. The observations can be reconciled if either 1) the increase in force is caused by a progressive increase in the attachment time of a constant number of cross bridges that cycle at a lower frequency or 2) the decline in energy expenditure caused by the slowing of cross-bridge cycling is sufficient to mask the increase caused by the recruitment of additional cross bridges.

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Cardiac energetics and the Fenn effect.

The energy output of a cardiac contraction can be divided into several phenomenologically measured components, although it must be emphasized that such subdivisions are often thermodynamically misleading. There is an activation term that relates to Ca++ release and retrieval, a work term and a stress or load-dependent heat term. The work and load-dependent energy terms presumably have their origin in the actin-activated myosin ATPase. It can be shown that the enthalpy: load relationship has a similar format across both mammalian and amphibian hearts: the scaling of both the energy and load axes is however altered by changes in contractility. The fact that enthalpy production is so clearly load-dependent indicates that there is a Fenn effect in cardiac muscle, although the discovery that energy output is greatest in an isometric contraction clearly contradicts one of the two central findings of Fenn's skeletal muscle investigations. Cardiac oxygen consumption per beat can be linearly correlated with ventricular systolic pressure--volume area (PVA) which is defined in terms of stroke work and potential energy components. If the basal and activation components are subtracted out cardiac muscle can be shown to operate at a constant PVA efficiency. The existing myothermic and polarographic data can be reconciled with the PVA concept.

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Energy expenditure of longitudinal smooth muscle of rabbit urinary bladder.

Heat production, oxygen consumption, and lactate production of longitudinal smooth muscle from rabbit urinary bladder has been measured at 27 degrees C. In isometric contractions (initiated by 1-Hz electrical stimulation) ranging in duration from 2 to 300 s, total energy expenditure correlated linearly with the force-time integral. For any given force-time integral oxygen consumption could account for only approximately 60% of the total energy measured as heat production. A substantial contribution of aerobic lactate production to the total energy flux was observed. This lactate production was also linearly correlated with force-time integral and was of sufficient magnitude to account for the discrepancy between total energy expenditure determined as heat production and oxygen consumption. The suprabasal rate of energy expenditure during the maintenance of force was approximately 2.6 mW/g and remained constant throughout contractions of up to 5-min duration, suggesting that in this muscle there is no change in the energetic cost of force maintenance with increasing duration of contraction. The rate of energy expenditure during the initial period of force development was, however, about twofold greater than that during subsequent force maintenance, indicating that there is an extra energy cost associated with the activation of contraction and development of force above that required for force maintenance.

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Daunomycin-induced cardiomyopathy in rabbits: isolated heart and papillary muscle energetics.

Daunomycin was administered to one of each pair of litter mate rabbits at a weekly dosage rate of 40 mg/m2. Treated animals were killed when their pre-ejection period: left ventricular ejection time ratio (PEP:LVET) reached 0.4 and there was other evidence of cardiac abnormalities or when they had received 12 doses of daunomycin. Langendorff-perfused hearts from the treated animals had lower intrinsic heart rates (16%) and decreased coronary resistance (31%) in the arrested state. There was no significant difference between the basal metabolism of the arrested control and treated hearts but the magnitude of the activation component, measured under beating non-working conditions, was depressed by daunomycin. After the whole heart perfusion studies were complete, approximately 2 h after cardiectomy, papillary muscles were dissected out from the right ventricles and mechanical, myothermic and polarographic studies were undertaken. The resting heat production, in support of the whole heart metabolic data, was practically unchanged by the treatment regime. Peak stress development and work output were similar in both the control and treated groups. In energetic terms the slope of the relationship between total stress development and active heat production per beat was unchanged but there was a 21% depression of the activation heat component in the treated animals. Daunomycin treatment had not altered the work output per contraction or significantly changed energy output and hence mechanical efficiency was unaltered. It is clear that 2 h of Langendorff perfusion does not produce any depression of contractile or energetic properties in papillary muscles.

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Factors regulating basal metabolism of the isolated perfused rabbit heart.

Basal metabolism has been measured in isolated whole hearts from rabbits and compared with myothermic and polarographic measurements on isolated papillary muscles. Hearts were perfused at constant pressure (Langendorff method) using a modified Krebs-Henseleit solution (KH) with glucose as substrate. Higher levels of basal O2 consumption (MVO2) and coronary flow (CF) were observed when arrest was induced by calcium depletion (low Ca; 0.1 mM CaCl2, 10.0 mM KCl) rather than by potassium excess (high K; 30.0 mM KCl). The metabolic rate of high K arrested hearts was close to earlier myothermic estimates (J. Mol. Cell. Cardiol. 16: 953-962, 1984); polarographic values, however, were about twofold higher, and somewhat higher than the value obtained in low Ca arrested hearts. The addition of erythrocytes, albumin, or dextran significantly reduced CF but did not substantially alter basal MVO2. Basal metabolic rate was substrate- and O2 tension-dependent, and under all experimental conditions there was linear relationship between MVO2 and CF. Extrapolations to zero flow showed that the basal MVO2 values so obtained were similar in low Ca or high K and were not altered by the presence of erythrocytes. Our results show that there are several factors regulating basal metabolism.

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Effect of duration of stimulation and pH on energetics of rabbit rectococcygeus muscle.

The mechanical and energetic performance of the rabbit rectococcygeus preparation have been studied at 27 degrees C. Energy flux has been measured either myothermically (heat production) or by recording the O2 consumption and lactate production of the muscle. The maximal active-to-basal O2 consumption ratio was 2.42. The peak oxidative energy flux was 3.5 mW/g, and the peak initial rate was about 5.0 mW/g. We could find no evidence for an increment in lactate production associated with mechanical activity. The effects of increasing the stimulus duration on the "economy" of force maintenance was assessed by plotting the heat-to-tension ratio against duration. For stimulus periods up to 20 s there was no evidence of a change in the economy: the slope of the relationship was similar in myothermic and O2 consumption experiments with split muscles. When total heat production was plotted against the stress-time integral for stimulus periods up to 60 s at both pH 7.4 and 6.7, there was no change in energy usage in the longer duration tetani (2-60 s). However, the reduction in pH, which had minimal mechanical effects other than prolonging relaxation, did slow the rate of evolution of recovery heat (time constant doubled) and reduced the rate of O2 consumption. It is concluded that the rectococcygeus preparation cannot make use of the energy-saving mechanisms that operate in arterial and several invertebrate smooth muscles.

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Cardiac mechanics and energetics: chemomechanical transduction in cardiac muscle.

When a heart is in a stable inotropic state, the end-systolic pressure-volume points of each work cycle fall on a straight line regardless of the magnitude of the afterload or the initial end-diastolic volume: cardiac O2 consumption (MVO2) per beat is linearly correlated with ventricular systolic pressure-volume area (PVA), defined in terms of stroke work and potential energy components. Moreover, if the basal and activation components of the cardiac energy cycle are subtracted, hearts operate at a constant PVA/MVO2 efficiency. The present review examines the energetic implications of these results for current muscle models, discussing the energetic background of earlier skeletal muscle viscoelastic models and examining differences between the vectorial outputs of ion transport ATPases and myofibrillar ATPases. The PVA data point to a unique stoichiometric relationship between myocardial energy flux and vectorial output, and it is shown that most existing myocardial O2 consumption data can be reconciled with the PVA concept. However, most muscle models would not predict a linear stoichiometric relation between energy flux and pressure-volume potential energy. We pose the question as to whether there is an undiscovered autoregulatory process at work in muscle.

Adenosine Triphosphate↗

Cardiac energetics in daunorubicin-induced cardiomyopathy.

Daunorubicin (DNR) was administered to one of each pair of litter mate rabbits at a weekly dosage rate of 40 mg/m2. Treated animals were killed when their pre-ejection period: left ventricular ejection time ratio (PEP:LVET) reached or exceeded 0.4. Mechanical, myothermic and polarographic measurements were made upon papillary muscles obtained from the right ventricle of DNR treated rabbits and their litter mate controls. DNR treatment significantly increased the PEP:LVET ratio (41%) and increased the left ventricular: body weight ratio (24%). Basal metabolism, measured 2 h after cardiectomy, was significantly reduced whether measured myothermically or polarographically: both measurements were highly correlated but the O2 consumption values were higher. Peak stress development was 31% lower in the DNR treated rabbits but this reduction was largely accounted for by a larger cross-sectional area (CSA) of the papillary muscles in this group. There was no change in the slope of the active heat: stress relationships but the stress-independent (activation) heat intercept was depressed. In isotonic studies DNR treatment caused a 57% reduction in work output per beat (relative to controls) and a 39% decline in active energy output. Because of the approximately parallel shift in work and total energy output mechanical efficiency was not significantly changed. It is suggested that part of the basal energy production fall produced by DNR relates to protein synthesis inhibition but that most of the other mechanical and energetic effects are probably explicable in terms of the intrinsic hypertrophic response of the 'failing' heart.

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Factors affecting the metabolism of resting rabbit papillary muscle.

The rate of resting heat production of 12 right ventricular rabbit papillary muscles was measured myothermically. Resting heat rate was measured at 4 temperatures (15, 20, 25 and 30 degrees C) in either 45% or 95% O2 while the muscle was passively stretched with various pre-loads. The metabolic substrate was pyruvate (10 mmol X 1(-1)). The mean resting heat rate, averaged across all treatment conditions, was 2.88 mW/g with no significant difference between the two oxygen concentrations. The calculated Q10 of the resting heat rate was surprisingly low--only about 1.4--but is shown to be in general agreement with literature values from whole heart oxygen consumption studies when the time-dependent decline is taken into account. Stretching the muscle beyond its rest length increased the rate of resting heat production. This response appeared unrelated to muscle diameter. The results are discussed in terms of the possible diffusion limitation of isolated papillary muscle preparations.

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Myothermic, polarographic, and fluorometric data from mammalian muscles: correlations and an approach to a biochemical synthesis.

Energy output of mammalian cardiac, smooth, and skeletal muscles has been studied by recording oxygen consumption, heat production, the fluorescence of reduced nicotinamide adenine dinucleotide (NADH), and lactate production. Active oxygen consumption and heat production of all muscle types correlate well if one assumes a calorific equivalent of 20.2 kJ/liter of oxygen. At 27 C aerobic lactate production is low in all muscle types and is not appreciably increased after mechanical activity. Early oxidation of NADH within the time course of the mechanical event suggests that no temporal basis exists for distinguishing between initial and recovery heat production in mammalian muscles. For muscles consuming energy at low rates, the time course of fluorescence recovery to baseline correlates well with the time course of late heat production, and the area enclosed by a fluorescence waveform (fluorescence-time integral) correlates well with total energy consumption. At high energy rates these correlations disappear as the fluorescence waveforms display complex kinetics. A digital computer simulation of oxidative phosphorylation and intermediary metabolism predicts failure of correlation between mitochondrial NADH levels and other metabolic indices under such conditions. This lends indirect support to the assumption that cytoplasmic NADH does not complicate the fluorescence signals recorded from aerobic unpoisoned muscles.

Adenosine Diphosphate↗

Cardiac energetics in short and long term hypertrophy induced by aortic coarctation.

Hypertrophy was induced in rats by constriction of the abdominal aorta proximal to the coeliac trunk. The effects of both short-term, STH. (2 to 4 days) and long term, LTH (40 to 55 days) hypertrophy were studied by mechanical and myothermic measurements on papillary muscles from the left ventricle. In agreement with other studies aortic coarctation increased the left ventricle to body weight ratio. In isometric experiments it was shown that peak stress development was enhanced in the STH group compared with the control and LTH groups. Active heat production was related to active stress development by linear regression in the control and pressure overload groups. There was no significant difference between the mean slopes of the groups but there was a significant increase in the intercept in the STH group and a decrease in the LTH group. This intercept corresponds to the tension-independent heat component. In isotonic experiments load enthalpy relationships were determined for the different groups and the data for each group were pooled. In the LTH group there was a 19% fall in work output per contraction and a 20% fall in total enthalpy. In the STH group there was a 31% increase in work output and a 39% rise in total enthalpy. Because of the parallel changes in work and enthalpy there was no significant change in the mechanical efficiency of the two groups as compared to the controls. The simplest interpretation of the results is that in STH the intracellular free calcium level is raised whereas in LTH it is lowered.

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Effect of temperature on mechanical and myothermic properties of rabbit smooth muscle.

The mechanical performance and the heat production of 18 rabbit rectococcygeus muscles have been measured at 19 degrees C and 29 degrees C. The rate of energy liberation in a tetanus was 2.96 +/- 0.14 mW/g at 19 degrees C and 5.84 +/- 0.25 mW/g at 29 degrees C. At both temperatures there was a linear relationship between total (initial + recovery) heat production and the stress-time integral for stimulus durations up to 13 s. The slope of the relationship had a Q10 of 1.8. Recovery heat evolution, measured after mechanical relaxation was complete, was approximately exponential in character. The final time constant for recovery heat liberation was 63.1 +/- 5.5 s at 19 degrees C and 32.3 +/- 2.4 s at 29 degrees C. After-loaded isotonic force-velocity data were fitted with the hyperbolic version of Hill's characteristic equation (A. V. Hill. Trails and Trials in Physiology. London: Arnold, 1965). The a/Po ratio was practically temperature independent, but maximal shortening velocity and the constant b had Q10's of 2.5 and 2.7, respectively.

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The influence of calcium on short-term memory.

Using a passive avoidance behavioural task in day-old chickens, it is possible by intracranial injection of appropriate drugs to separate out three phases of memory formation. The duration of the first such phase, called short-term memory, is increased when the intracranial calcium ion concentration is raised and the phase is practically abolished by injection of lanthanum ions.

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Cardiac heat production.

The energy production (heat + work) of cardiac muscle must be interpreted in terms of the major ATPases underwriting cardiac contraction; these are the Ca2+ and Na+-K+ transport ATPases and actomyosin ATPase. It is possible to apply the classical phenomenological subdivisions to cardiac energy production; when this is done, certain properties immediately distinguish cardiac muscle from skeletal muscle. Little or no temporal distinction exists between initial (anaerobic) and recovery (oxidative) metabolism. Even at temperatures as low as 20 degrees C most of the recovery heat is released within the time course of a single contraction. Cardiac muscle is characterized by a high resting heat rate, the magnitude of which varies between species and depends on the metabolic substrate. In isometric contractions there is a slightly curvilinear relationship between developed force and heat production. There is a tension-independent or activation component, the magnitude of which reflects the prevailing level of contractility and is probably associated with calcium release and retrieval. In isotonic contractions energy production is maximal when the muscle is heavily loaded but falls steeply when the size of the load is reduced. The enthalpy:load relation is probably similar to that found in twitch contractions of skeletal muscle working at room temperature or above; but, unlike for skeletal muscle, there are families of such curves: At any instant of time the relation depends upon the prevailing physiological conditions (e.g. stimulus rate, substrate supply, humoral agents, extracellular ionic concentrations, initial length). Cardiac energy production can be estimated by a variety of other techniques (such as high-energy phosphate utilization, oxygen consumption, and changes in tissue fluorescence related to pyridine nucleotide oxidation levels). At the present time there is considerable agreement between heat measurements and results obtained with these different techniques. We should like to conclude on a cautionary note. First, there is considerable variability in the properties of cardiac muscle from different species. Significant variations occur at nearly all levels of cellular function--e.g. shape of action potential, electrical and mechanical dependence upon stimulus history, mechanisms of excitation-contraction coupling, actomyosin ATPase activity, metabolic regulation, and differential sensitivity to anoxia or ischemia. Second, the types of contractions readily studied in isolated papillary muscles (i.e. isometric or isotonic twitches) may not necessarily be the best mechanical paradigms for understanding myocardial energetics in vivo. The particular geometric demands of individual research techniques require the use of a wide variety of myocardial preparations from a wide variety of species. This necessarily produces a pastiche view of cardiac muscle rather than an integrated picture of some hypothetically typical mammalian myocardium.

Adenosine Triphosphatases↗

Species differences in cardiac energetics.

The energy flux of rat, guinea pig, and cat papillary muscles was measured myothermically under resting, isometric, and isotonic conditions at 27 degrees C. Resting heat rate was highest in the smallest species and declined with body size. The slope of the isometric heat-stress relationship was constant across species, whereas the stress-independent heat component was least for rat muscles. The shape of the load enthalpy relationship was similar across species. Maximum mechanical efficiency, work-enthalpy, occurred with lighter loads than for skeletal muscle (approximately 0.2 Po). Rat muscle had the smallest enthalpy per beat and the highest active mechanical efficiency, but this advantage was nullified by the higher basal heat rate. The myothermic data are compared with cardiac oxygen consumption values in the literature and it is concluded, contrary to the deductions of common dimensional arguments, that cardiac energy expenditure across species is not directly proportional to heart rate. Reasons for this discrepancy are considered together with the likely contribution of cardiac metabolism (EH) to total body metabolism (EB). It seems likely that smaller species have lower EH/EB.

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