Search PubMed⌕ Search

Biomedical subjects

I R Wendt

Publications and source records attributed to I R Wendt.

At least 37 records · Page 2Linked to original sources
PubMed1990

Mechanical, energetic, and biochemical changes in long-term pressure overload of rabbit heart.

The mechanical and energetic consequences of long-term pressure-overload (POL) hypertrophy have been investigated in rabbits and compared with sham-operated controls (SOC). Hypertrophy was induced by banding the pulmonary artery of young rabbits and examining the mechanical, biochemical, and energetic properties of the compensated heart 10-16 wk later. Experiments were undertaken on papillary muscles from the hypertrophic hearts. At 27 degrees C and a stimulus frequency of 1 Hz there was a modest depression of peak stress development but no significant changes in isometric rise times and one-half widths or in isotonic maximum velocity of shortening and power output. The inverse relationship between peak stress and cross-sectional area (CSA) was practically identical in the POL and SOC groups. Both polarographic and myothermic investigations were made on papillary muscles. Hypertrophy nearly halved basal metabolism, and in isometric contractions there was increased isometric economy due to a combination of a lower stress cost and a reduced activation heat. Hypertrophy did significantly depress the extent of shortening leading to a reduced work output per beat. In isotonic contractions the reduced work output was offset by a reduced energy output such that there was no significant change in suprabasal mechanical efficiency. Biochemical studies showed that the transition of myosin isoenzymes to the V3 form was essentially complete in the POL group, but that the SOC group was also predominantly V3 when the animals were killed. There was a significant 30% decline in the Ca2(+)-stimulated adenosinetriphosphatase activity of the sarcoplasmic reticulum. It is concluded that in long-term compensated hypertrophy of rabbit hearts there are only a few mechanical and energetic differences between control and hypertrophic muscles. The changes that can be detected appear to predominantly reflect disturbances in cellular Ca2+ regulation.

Animals↗
PubMed1990

Smooth muscle energetics: testing theories of crossbridge regulation.

Our results indicate that the kinetic "latch" model of Hai & Murphy is not very sensitive to the proportion of ATP assigned to crossbridges relative to that ascribed to MLC phosphorylation/dephosphorylation. Thus the basis for the relatively low efficiency of smooth muscle, attributed to high MLC phosphorylation/dephosphorylation in this model, remains open to question. Moreover, this model, or any model with mixed populations of crossbridges with differing cycle rates and/or high MLC phosphorylation/dephosphorylation rates is unlikely to account for the observed linearity of JATP and stress reported for many smooth muscles. Our studies comparing the heat production of intact and skinned smooth muscle indicate that the ATPase associated with myosin phosphorylation/dephosphorylation is unlikely to be a major factor in the tension cost of intact smooth muscle. Thus it would appear that energetics places considerable constraints on current theories of crossbridge regulation. Our modelling (Paul, 1989) suggests that it may be time to reevaluate Bozler's original hypothesis that a high attachment:detachment rate ratio for smooth muscle actin-myosin interaction may be sufficient to explain the energetics of smooth muscle.

Adenosine Triphosphate↗
PubMed1989

Energy metabolism in the perfused, arrested rabbit heart.

Energy metabolism of quiescent cardiac muscle was studied in the isolated rabbit heart preparation perfused at constant pressure by the Langendorff technique. Oxygen consumption (MVo2), coronary flow rate (CFR) and the steady state concentrations of high energy phosphate compounds were determined in hearts rendered asystolic using modified Krebs-Henseleit (KH) media containing 11 mM glucose as substrate. Basal MVo2 and CFR were significantly higher in hearts arrested by Ca2+ depletion (low Ca KH) compared to K+ excess (high K KH). Substitution of glucose in low Ca KH with a mixture containing glutamate, fumarate and pyruvate (low Ca KH + GFP) resulted in a 25% increase in the basal MVo2 but a 20% decline in CFR. Supplementing the low Ca perfusate with 30 g/l dextran (low Ca KH + dextran) depressed both the basal MVo2 (35%) and CFR (75%). Differences in the basal MVO2 under the different perfusion conditions were not accompanied by significant changes in the tissue levels of ATP, CrP or Cr. Compared to low Ca KH arrested hearts, those perfused with low Ca KH + GFP or low Ca KH + dextran did, however, show significantly lower tissue levels of ADP, AMP and Pi, but higher cytosolic ratios of [ATP]/[ADP][Pi] and [CrP]/[Cr][Pi]. As a consequence of the higher phosphorylation potential the free energy of ATP hydrolysis increased. There was no significant difference in any of these parameters between high K KH and low Ca KH perfused hearts. It is concluded that in the perfused, arrested heart none of the parameters that are used to describe the myocardial energetic state, e.g. free [ADP] or the cytosolic [ATP]/[ADP][Pi] ratio, uniquely correlates with the basal metabolic rate as estimated from MVO2 measurements.

Adenine Nucleotides↗
PubMed1989

Effects of substrate and hypoxia on smooth muscle metabolism and contraction.

Suprabasal heat production, oxygen consumption, and lactate production were measured, together with force, in 30-s isometric contractions of longitudinal smooth muscle from rabbit urinary bladder at 27 degrees C. Either glucose or pyruvate was provided as exogenous substrate. Under aerobic conditions with glucose as substrate, force averaged 95 mN/mm2 and heat production 121 mJ/g. Oxygen consumption (0.18 mumol/g) could account for only two-thirds of the total energy expenditure represented as heat production. The remaining one-third was accounted for by aerobic lactate production (0.36 mumol/g). When pyruvate replaced glucose as substrate, both the force developed and the total heat liberated were unchanged. Oxygen consumption, however, increased by approximately 40% (to 0.25 mumol/g) and was able to fully account for the measured heat production. The frequency of spontaneous contractions under aerobic conditions was always reduced in the presence of pyruvate. Under anaerobic conditions force was essentially unaltered, and heat production was only slightly reduced (101 mJ/g) with glucose present. Lactate production increased threefold over that under aerobic conditions. With pyruvate as substrate both force and heat production declined markedly (to less than 5% of the aerobic values). The results indicate that under aerobic conditions and with glucose as substrate, smooth muscle of rabbit urinary bladder generates about one-third of its suprabasal energy requirements through glycolysis and that glycolysis can be further accelerated under anaerobic conditions to provide sufficient energy to sustain contraction. If pyruvate replaces glucose as substrate, the metabolism shifts to being virtually all oxidative, and contraction can no longer be sustained in the absence of oxygen.

Anaerobiosis↗
PubMed1988

Transducing chemical energy into mechanical function: a comparative view.

The energetics of muscle contraction can be understood in terms of the major cellular ATPases. The twitch isometric transduction efficiency is relatively constant across muscle types and species. Although many of the factors that alter the shape of the enthalpy:load relation in isotonic twitch contractions have been identified our molecular understanding is unsatisfactory and more studies are needed of mammalian muscles working closer to 37 degrees C. The thermodynamic efficiency of CB activity seems quite high, probably in excess of 70%. During maintained (tetanic) force there can be greater than a 1000 fold difference in energy usage across muscle types and there are factors that can down regulate CB activity: these factors remain to be fully identified in both skeletal and smooth muscles. The very diversity of muscle types and the different biochemical solutions that have emerged to match energy supply and demand should lead to important insights into the contractile mechanism. The corollary however also applies, it may be dangerous to take results obtained in one muscle type under a particular set of conditions, and extrapolate those findings to muscles in general.

Adenosine Triphosphatases↗
PubMed1988

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.

Animals↗
PubMed1988

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.

Animals↗
PubMed1987

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.

Animals↗
PubMed1986

Effects of procaine on calcium accumulation by the sarcoplasmic reticulum of mechanically disrupted rat cardiac muscle.

The ability of the sarcoplasmic reticulum of skinned cardiac muscle of the rat to accumulate and release Ca2+ was studied in the presence and absence of procaine. Ca2+ accumulation was estimated from the magnitude of the caffeine- (30 mM) induced force transient in a weakly Ca2+ buffered solution. The relative area under the caffeine-induced force transient was up to 4-fold greater when 5 mM-procaine had been present during the preceding period of Ca2+ loading, than that after an equivalent period of Ca2+ loading in the absence of procaine. Procaine antagonized the caffeine-induced release of Ca2+ when present in the Ca2+ releasing solution, however, the ability of procaine to attenuate the caffeine-induced Ca2+ release diminished as the extent to which the sarcoplasmic reticulum was loaded with Ca2+ increased. In the presence of 1 mM-Mg2+ procaine also markedly attenuated the small spontaneous force oscillations (5-10% P0) associated with the cyclic release and reuptake of Ca2+ by the sarcoplasmic reticulum. When the Mg2+ concentration was reduced to 0.1 mM, procaine initially suppressed the small spontaneous oscillations in force, however, large force oscillations (40-80% P0) of lower frequency were invariably initiated after 20-60 s exposure to 5 mM-procaine. Procaine (5 mM) produced a slight shift (approximately 0.04 pCa unit) of the force-pCa relation toward lower Ca2+ concentrations. This effect is too small to influence in any substantial way the apparent effects of procaine on the sarcoplasmic reticulum. The results indicate that whilst procaine is indeed able to suppress Ca2+ release under certain circumstances, in its presence the net accumulation of Ca2+ by the sarcoplasmic reticulum can be markedly enhanced.

Animals↗
PubMed1983

Effects of caffeine on Ca-activated force production in skinned cardiac and skeletal muscle fibres of the rat.

Skinned fibres prepared by mechanical and/or chemical means from cardiac and skeletal muscles of the rat were activated in solutions strongly buffered for Ca2+ (with 50 mM EGTA) in the absence or presence of caffeine 5-40 mM. In all preparations caffeine was found to reversibly shift the relation between steady-state force and free [Ca2+] toward lower free [Ca2+] in a dose dependent manner. This increase in apparent Ca2+ sensitivity was not antagonized by procaine and was the same, within each muscle type, irrespective of the manner in which the skinned fibre was prepared, and consequently the degree to which it retained cellular membranes. The effect was more pronounced in cardiac and slow-twitch than in fast-twitch, myofibrillar preparations. At equivalent concentrations theophylline mimicked this effect of caffeine in all preparations, however, addition of exogenous cyclic AMP neither mimicked nor modified, in any way, the effect. Maximum Ca2+ -activated force production was not affected by caffeine below 20 mM but was depressed by concentrations of 20 mM and above. The increase in apparent Ca2+ sensitivity produced by caffeine can not be the result of a mobilization of some cellular store of Ca2+ but must arise from a direct effect of caffeine on the myofilaments which leads to a change in the apparent affinity constant of the force controlling sites for Ca2+.

Animals↗
PubMed1982

Energetic consequences of thyroid-modulated shifts in ventricular isomyosin distribution in the rat.

Heat production (measured myothermically), force development and isomyosin distribution were measured in left ventricular papillary muscles from adult male rats in three thyroid states: hyperthyroid (T3), euthyroid (C) and hypothyroid (Tx). Rats were rendered hyperthyroid by daily injections of tri-iodothyronine and hypothyroid by radioisotopic thyroidectomy. Papillary muscle performance was measured both for trains of isometric twitches and for brief (2 s) tetani achieved by increasing the Ca2+ concentration and adding caffeine to the bathing solution. Resting metabolic rate was uninfluenced by thyroid state. Heat-stress relations were determined for both twitches and tetani by altering muscle length. Tx muscles showed an elevated stress-independent or activation heat (intercept of the heat-stress relation), a depressed stress-dependent heat (slope of the heat-stress relation), and greatly enhanced peak twitch and tetanic (Smax) stresses. When normalized for Smax, the maximal rates of tetanic stress development and heat production were depressed in the Tx group. In the T3 group, only the normalized maximal rate of tetanic stress development was significantly increased. The lack of significant effects on other mechanical and energetic parameters probably reflects an under-dosing of animals in this tri-iodothyronine-treated group, an interpretation supported by the modest change in isomyosin distribution resulting from the treatment regimen used. Separate isomyosin analyses of papillary muscles and their associated ventricles yielded excellent correlation demonstrating the suitability of papillary muscles as a model of ventricular wall tissue. By experimentally manipulating the thyroid state, the distribution of the three ventricular isomyosins were correspondingly altered with a shift toward a greater and lesser proportion of high activity myosin ATPase in the hyperthyroid and hypothyroid groups respectively. The average proportions of the myosin heavy chain associated with high actin-activated myosin ATPase were 86, 74 and 6% for groups T3, C and Tx respectively. The measured changes in papillary muscle energetics correlate well with these thyroid-induced changes in isomyosin distribution and can be explained in terms of altered crossbridge dynamics.

Analysis of Variance↗
PubMed1981

Non-uniform ion distributions and electrical potentials in sarcoplasmic regions of skeletal muscle fibres.

We report here electrophysiological and ion distribution results obtained with mechanically skinned skeletal muscle fibres which indicate that a Donnan equilibrium, characterized by large ionic concentration and electrical potential differences, is established between the myofibrillar space and the rest of the sarcoplasm surrounding the myofibrils. The more negative electrical potential within the myofibrils (-15 to -29 mV for conditions similar to those in vivo) can strongly influence: (1) intracellular Ca2+ movements associated with contraction; (2) the location of sarcoplasmic enzymes, their substrates and products of reaction; (3) measurements of the electrical potential difference between the extra- and intracellular space and estimation of relative membrane permeabilities for certain ions.

Animals↗
PubMed1977

Effects of the antibiotic ionophore X-537A on contractility and ionic exchange in rabbit ventricular myocardium.

The effects of the ionophore X-537A on mechanical function and on ionic exchange were studied in the isolated, arterially perfused rabbit interventricular septum. X-537A produced an initial positive inotropic response which was, however, transient in this preparation and appeared to be dependent on an effect of the ionophore on catecholamines. The positive inotropy gave way to a progressive decline in force development which was unrelated to the action of catecholamines and was not accompanied by the development of contracture. Isotope uptake experiments revealed that coincident with this decline in force development there was a continuous net loss of tissue K+ and a net gain of Na+. X-537A (5 micronM) perfused for 20 minutes resulted in a net K+ loss of 50.2 +/- 4.6 mmol/kg dry weight and a net Na+ gain of 74.0 +/- 4.5 mmol/kg dry weight. Isotope washout experiments confirmed that the entire net loss of K+ could be accounted for by increased K+ efflux. X-537A did not alter Na+ efflux nor did it have any detectable effect on 45Ca exchange of the perfused septum in which the ability to detect net movements is at a level of approximately +/- 550 micron mol/kg dry weight. On removal of the ionophore the decline in force development ceased and reversed to near control levels and the progressive ionic changes ceased. However, despite the near total recovery of contractile function the Na+ and K+ levels remained at values little different from those reached at the termination of X-537A perfusion. In addition, after removal of the ionophore, we found that K+ exchange rate remained significantly less than control and, furthermore, a kinetic inhomogeneity of tissue K+ was observed. The results emphasize a dissociation between cellular Na+ and K+ content and function following the ionic perturbations induced by the ionophore.

Animals↗