The effect of increasing extracellular potassium concentration on the resting heat rate of the isolated rat papillary muscle

The effect of elevating extracellular K⁺ concentration on the basal metabolism of the isolated rat left ventricular papillary muscle has been investigated. The preparation was mounted on a thermopile and connected to a force transducer, to allow simultaneous measurement of muscle heat production and force. The resting heat rate (RHR) of the quiescent preparation was measured as an index of basal metabolism. Throughout all of the experiments, the muscles were maintained under a resting force of 10 mN and all measurements of RHR were made at times when there was no active force present above this passive level. Elevating the extracellular K⁺ concentration from 5.9 to 20, 40, then 80 mM produced graded increases in the RHR. The increase in RHR produced by 40 mM K⁺ was observed to be time-dependent, its effect being significantly greater at 5–7 h than at 2–4 h after cardiectomy. Averaged over all times, the percentage increases in RHR produced by 20, 40, and 80 mM K⁺ in the presence of 2 mM Ca²⁺ were 6.4±2.0%, 28.7±2.3%, and 51.3±8.9% (mean±SEM) respectively. The high K⁺-induced increase in basal metabolism was also shown to be Ca²⁺-dependent, the increase in RHR produced by 40 mM K⁺ being greater the higher the extracellular Ca²⁺ concentration (0.5–8.0 mM). The addition of verapamil was found to partially inhibit the K⁺-induced increase in resting metabolism. These results show that elevation of the extracellular K⁺ concentration produces a graded increase in the RHR that is Ca²⁺-dependent. It is suggested that the increases in RHR observed in this investigation are in part associated with elevated levels of myoplasmic free Ca²⁺ which stimulate the internal Ca²⁺ pumps.     

The effects of temperature on the energetics of rat papillary muscle

The mechanical and myothermic responses of left ventricular papillary muscles from adult rats have been examined at 20° and at 27°C. Contraction trains of six isometric or isotonic twitches at 1/6 Hz were used to establish the heat-stress and load-enthalpy relations respectively. Peak isometric stress was slightly higher at 20° than at 27°C (45 vs. 41 mN/mm²) and was inversely related to muscle cross-sectional area. The stressindependent heat component, identified with the activation heat, was 75% greater at the lower temperature. The stress-dependent heat component, identified with the heat of actin-myosin interaction, was unaffected by temperature. In isotonic experiments the external work performance was similar at both temperatures but the heat liberation was significantly enhanced at the lower temperature so that mechanical efficiency (external work/enthalpy) was reduced. Evidence is presented suggesting that the preparations were not O₂-diffusion limited at either temperature. The results are discussed in terms of the known functional anomalies of rat cardiac tissue.     

Recovery heat production of isolated rabbit papillary muscle at 20°C

Using metal-film thermopiles, heat production of isolated rabbit papillary muscles was measured under aerobic conditions at 20°C. The time course of total heat production resulting from a single contraction (average of 10) and a twitch train of 10 contractions (0.2 Hz) was separated into initial (I) and recovery heart (R). The time course of recovery heat production of single twitches was characterized by a time constant of 25.4±1.7 s (mean±SE;n=10). The recovery ratio,R/I, was 1.18±0.08 (mean±SE;n=7). Total heat produced 25.2±2.9mJ·g _dw ^–1 (mean±SE;n=11). After trains of 10 contractions a time constant of 25.2±1.6 s (mean±SE;n=9) was found. The recovery ratio was 1.14±0.09 (mean±SE;n=9). Total heat produced was 489±41 mJ·g _dw ^–1 (mean±SE;n=9). Time constants and recovery ratios for 1 and 10 twitches were not significantly different. This suggests that only the extent but not the nature of the chemical processes after contraction changes when the preparation produces about 20 times more heat. Since the recovery ratio values did not differ largely from the value derived theoretically the conclusion is justified that, under normal aerobic conditions, PCr splitting and its oxidative resynthesis are the major metabolic processes responsible for the energy supply of isolated cardiac muscle.     

The effect of temperature on the basal metabolism of cardiac muscle

Using independent methods, measurements were made of the rate of oxygen consumption of quiescent rat ventricular tissue slices and of K⁺-arrested rabbit hearts at different temperatures. Experiments were designed such that the effect of temperature could be separated from the effect of time. The rate of oxygen consumption of both cardiac muscle preparations declined with time following cardiectomy. Likewise the rate of resting oxygen consumption of both preparations was relatively insensitive to temperature: Q₁₀=1.3. By contrast, the rate of oxygen consumption of rat liver slices showed a Q₁₀ of 2.6. The low Q₁₀ values of the cardiac preparations do not appear to be due to an inadequate supply of oxygen. The results are in close agreement with those of myothermic studies.A preliminary account of this research was presented to the Australasian Section of the International Society for Heart Research, Auckland, New Zealand, August 1982 (J Mol Cell Cardiol 14, suppl 2. p 10)     

Dynamics of oxygen uptake following exercise onset in rat skeletal muscle

Technical limitations have precluded measurement of the V(O(2)) profile within contracting muscle (mV(O(2))) and hence it is not known to what extent V(O(2)) dynamics measured across limbs in humans or muscles in the dog are influenced by transit delays between the muscle microvasculature and venous effluent. Measurements of capillary red blood cell flux and microvascular P(O(2)) (P(O(2)m)) were combined to resolve the time course of mV(O(2)) across the rest-stimulation transient (1 Hz, twitch contractions). mV(O(2)) began to rise at the onset of contractions in a close to monoexponential fashion (time constant, J = 23.2 +/- 1.0 sec) and reached it's steady-state value at 4.5-fold above baseline. Using computer simulation in healthy and disease conditions (diabetes and chronic heart failure), our findings suggest that: (1) mV(O(2)) increases essentially immediately (< 2 sec) following exercise onset; (2) within healthy muscle the J blood flow (thus O(2) delivery, J Q(O(2)m)) is faster than JmV(O(2)) such that oxygen delivery is not limiting, and 3) a faster P(O(2)m) fall to a P(O(2)m) value below steady-state values within muscle from diseased animals is consistent with a relatively sluggish Q(O(2)m) response compared to that of mV(O(2)).     

Cyclic AMP but not phosphorylation of phospholamban contributes to the slow inotropic response to stretch in ferret papillary muscle

 cAMP has been suggested to mediate the increased intracellular Ca²⁺ transient and contraction seen during the slow response to stretch in cardiac muscle. We measured cAMP in ferret papillary muscles stretched from 80–85% to 98% of their length at which maximum active tension is produced (L _max) for 15 min. cAMP was significantly (P<0.05) increased by 53% in muscles at the longer length which showed the slow response compared with controls. By contrast, in a population of muscles that were stretched but did not show the slow response, cAMP was not significantly different from that in muscles at the short length. Although cAMP can increase sarcoplasmic reticulum (SR) Ca²⁺ uptake by phosphorylation of phospholamban, we found no significant effect of stretch on phosphorylation of phospholamban at either Ser¹⁶ or Thr¹⁷. Further support for the hypothesis that cAMP is a mediator of the slow response was obtained by exposure of some muscles to the cell-permeable cAMP antagonist 8-bromo, adenosine 3′,5′-cyclic monophosphorothioate, Rp isomer (Rp-8-Br-cAMPS, (2.5–10 μM). The slow response was reduced by 30% (P<0.05) in the presence of this antagonist. Our results not only provide evidence for the mediation of the slow response to stretch by cAMP, they also suggest that cAMP may rise in an intracellular compartment inaccessible to the SR. Received: 14 January 1999 / Received after revision: 15 February 1999 / Accepted: 16 February 1999     

The effect of applied mechanical vibration on two different phases of rat papillary muscle relaxation

 Applying external mechanical vibration during the relaxation phase of rat papillary muscle decreases the duration of the first part of the relaxation phase. To elucidate the basic mechanism responsible for this shortening of the relaxation period, we applied a controlled vibration to isolated twitching rat papillary muscles during various phases in the relaxation of a twitch. The first part of the relaxation phase was accelerated when length perturbations were applied in the first part of the relaxation of a twitch, dependent on both amplitude and frequency of the perturbation. When vibrations were applied in the first half of the relaxation, the second phase of relaxation was slightly slower (about 20%), but when no vibrations were applied in the first phase, relaxation could be accelerated by applying vibration in the latter half of the relaxation phase. Thus, in the latter half of relaxation, the acceleration of relaxation depended upon perturbation events earlier during that twitch. This study indicates that vibration-induced acceleration of relaxation is due (at least in part) to an apparent increase in detachment rate of attached cross-bridges from the thin filament without substantial reattachment. Received: 17 January 1997 / Accepted: 12 June 1997     

Role of heat loss and heat production in generation of the circadian temperature rhythm of the squirrel monkey

To study heat production and heat loss in determination of the daily body temperature rhythm, we examined colonic temperature, skin (tail, foot and abdomen) temperatures and oxygen consumption in chair-restrained squirrel monkeys maintained in isolation in an environmental chamber with a 24-hr light-dark cycle (LD 12:12), maintained at a constant thermoneutral temperature (26 degrees C). In all experiments repeated high amplitude (2 degrees C) diurnal rhythms in colonic temperature were observed. Heat loss, estimated from changes in skin temperature, also displayed a circadian rhythm, although there was considerable variation in waveform. On average, a rhythm in heat production, indicated by changes in the rate of oxygen consumption, was also present. However, a large degree of variability was seen in oxygen consumption, and in several cycles from various animals there were no observable 24-hr rhythms. The circadian body temperature rhythm is thus not simply a consequence of daily changes in metabolism, but rather a regulated response that involves both heat production and heat loss.     

The energetics of the quiescent heart muscle: high potassium cardioplegic solution and the influence of calcium and hypoxia on the rat heart

Heart basal metabolism has been classically studied as the energy expenditure of those processes unrelated to mechanical activity and often measured by rendering the heart inactive using cardioplegic solutions (usually by increasing extracellular K concentration ([K]_e). In arterially perfused rat heart (at 25 °C), raising [K]e from 7 to 25 mM at a constant extracellular Ca concentration ([Ca]_e) (0.5 mM ), induced an increase in resting heat production (Hr) from 4.1 ± 0.3 to 5.1 ± 0.3 mol. wt g^?1. Under 25 mM K additional increase in [Ca]_e further increased Hr to 6.0 ± 0.4, 7.0 ± 0.4 and 8.3 ± 0.9 mol. wt g^?1 for 1, 2 and 4 mM Ca, respectively. While under 7 mM K perfusion Hr was not affected by 4 μM verapamil, under 25 mM K and 2 mM Ca 0.4 μM verapamil induced a decrease in Hr (?1.6 ± 0.2 mol. wt g^?1, n = 5, P < 0.001). Caffeine increased Hr under 0.5 mM Ca and 7 mM K perfusion (+0.32 ± 0.06 and +1.19 ± 0.25 mol. wt g^?1 for 1 and 5 mM caffeine respectively), but under 25 mM K conditions Hr was not affected by caffeine 2 mM . Severe hypoxia decreased Hr under both 7 and 25 mM K (3.7 ± 0.5 to 2.7 ± 0.4 mol. wt g^?1 and 7.0 ± 0.4 to 2.2 ± 0.5 mol. wt g^?1, respectively) suggesting that the increased Hr associated with the verapamil sensitive fraction of heat released is associated to a mitochondrial mechanism. Therefore, the use of high [K]_e overestimates basal values by increasing a verapamil sensitive fraction of the energy released. In addition, high [K]_e modifies a caffeine sensitive energy component probably due to a depletion of caffeine-dependent Ca stores.     

Allometric scaling of maximal metabolic rate in mammals: muscle aerobic capacity as determinant factor

Maximal metabolic rate (MMR) of mammals scales differently from basal metabolic rate (BMR). This is first shown by scrutinizing data reported on exercise-induced Vo2 max in 34 eutherian mammalian species covering a body mass range of 7 g-500 kg. Vo2 max was found to scale with the 0.872 (+/-0.029, 95% confidence limits 0.813-0.932) power of body mass which is significantly different from the 3/4 power reported for basal metabolic rate. The aerobic scope is higher in athletic than non-athletic species, and it is also higher in large than in small species. Integrated structure-function studies on a subset of 11 species (body mass 20 g-450 kg) show that the variation of Vo2 max with body size is tightly associated with the aerobic capacity of the locomotor musculature: the scaling exponents for Vo2 max, the total volume of mitochondria, and the volume of capillaries are nearly identical. The higher Vo2 max of athletic species is tightly linked to proportionally larger mitochondrial and capillary volumes in animals of the same size class. As a result Vo2 max is linearly related to both total mitochondrial and capillary erythrocyte volumes. We conclude that the scaling of maximal metabolic rate is explained by features and mechanisms different from those determining basal metabolic rate.     

牛磺酸对大鼠止血带休克的影响

在大鼠止血带休克(ToS)模型上,观察到口服牛磺酸增加动物组织牛磺酸含量,可有效地避免ToS大鼠血压的进行性降低,减少胞浆酶和溶酶体酶的漏出,抑制组织脂质过氧化的发生,阻止骨骼肌线粒体钙积聚和延长动物存活时间。而应用β-丙氨酸减少动物组织牛磺酸含量使休克加重,缩短动物存活时间。结果提示,牛磺酸可能参与机体在缺血—再灌注损伤时的防御反应。     

The stiffness of parallel elastic elements in rat papillary muscle

Summary The dynamic stress-strain relationship of the parallel elastic element (PE) in rat papillary muscle has been investigated.This relationship cannot be correctly estimated by means of the classical diagram: muscle length-stable passive tension of the whole muscle. A new experimental approach has been developed by which the elastic properties of PE may be measured under dynamic conditions.After isometric stabilization of the muscle at a series of preloads, tension changes following quick release were measured. The tension-length relationships measured under these conditions were used to evaluate the elastic behaviour of the parallel elements.The results obtained show that the stiffness of PE is higher than expected and that its maximum elongation never exceeds 10% of the respectiveL _o value at all preload levels explored.Preliminary communication at: International Congress of Physiological Sciences, Munich, July 1971. This study was partially supported by a grant from the Consiglio Nazionale delle Ricerche (CNR, Rome, Italy).     

The increase in the rate of heat production of frog's skeletal muscle caused by hypertonic solutions

1. The rate of heat production of resting muscle is increased by hypertonic solutions.2. The threshold osmolality required to produce the increased heat rate is less than 2 times normal; at 2.5-3 times normal the heat production rises to 20-50 mcal.g(-1).min(-1), which is 10-20 times the basal rate.3. In anaerobic conditions, the effect of hypertonic solutions on heat rate is only one tenth of that in aerobic conditions.4. A glycerol-treated muscle, with damaged tubular system, still gives a normal response to hypertonic solutions, though it does not respond to raised K(+) concentration.5. The metabolic response to hypertonic solutions is considerably suppressed by procaine.6. Ouabain, 10(-5)-10(-4)M, has no effect.7. The response remains substantial in a muscle which has been depolarized in isotonic K(2)SO(4).8. The membrane potential is slightly reduced by hypertonic solutions, but this cannot account for the increase of the resting metabolism.9. It is suggested that the effect may be due to the release of calcium ions, which produce an increase in myosin ATPase activity.     

The rate of muscle temperature increase during acute whole-body vibration exercise

This study compared the rate of muscle temperature (T _m) increase during acute whole-body vibration (WBV), to that of stationary cycling and passive warm-up. Additionally we wanted to determine if the purported increase in counter-movement jump and peak power cycling from acute WBV could be explained by changes in muscle temperature. Eight active participants volunteered for the study, which involved a rest period of 30 min to collect baseline measures of muscle, core, skin temperature, heart rate (HR), and thermal leg sensation (TLS), which was followed by three vertical jumps and 5 s maximal cycle performance test. A second rest period of 40 min was enforced followed by the intervention and performance tests. The change in T _m elicited during cycling was matched in the hot bath and WBV interventions. Therefore cycling was performed first, proceeded by, in a random order of hot bath and acute WBV. The rate of T _m was significantly greater (P < 0.001) during acute WBV (0.30°C min⁻¹) compared to cycle (0.15°C min⁻¹) and hot bath (0.09°C min⁻¹) however there was no difference between the cycle and hot bath, and the metabolic rate was the same in cycling and WBV (19 mL kg⁻¹ min⁻¹). All three interventions showed a significant (P < 0.001) increase in countermovement jump peak power and height. For the 5 s maximal cycle test (MIC) there were no significant differences in peak power between the three interventions. In conclusion, acute WBV elevates T _m more quickly than traditional forms of cycling and passive warm-up. Given that all three warm-up methods yielded the same increase in peak power output, we propose that the main effect is caused by the increase in T _m.     

Combined inhibitory actions of acidosis and phosphate on maximum force production in rat skinned cardiac muscle

Possible interactions between the effects of pH and phosphate (Pi) on the maximum force development of cardiac myofibrils were investigated in rat skinned trabeculae in solutions of different pH (7.4-6.2) and [Pi] (where [ ] denote concentration). At pH 7.0 there was an inverse linear relationship between force and log [Pi] over the [Pi] range 0.2–20 mM; its slope (–0.46/decade) was twice that found previously for skeletal muscle [21]. Acidosis depressed force substantially, but the relative change of force was unaffected by Pi addition (0, 5, 20 mM); there was no evidence for the synergism between acidosis and Pi that would be expected if some of the inhibition by acidosis was due to protonation of Pi to the putative inhibitory form, H₂PO ₄ ^– . It was taken into account that even without Pi addition, there was enough Pi inside the muscle from various sources to produce significant changes in [H₂PO ₄ ^– ] as the pH was varied. The results suggest that H⁺ and Pi inhibit maximum force development of cardiac myofibrils independently, by different mechanisms. From this it is argued that H⁺ and Pi may be released at different steps in the crossbridge cycle. In the myocardium Pi and H⁺ probably exert tonic inhibitory influences on cardiac myofibrils under all conditions.     

The effects of exercise duration on dynamics of respiratory gas exchange,ventilation, and heart rate

This study investigated the effect of exercise duration on the response dynamics of oxygen consumptionVO₂, carbon dioxide outputVCO₂, ventilation V_E), and cardiac frequency (f _c) following stepped changes in exercise intensity, by manipulating the duration of the pretransition exercise period. A group of 11 healthy men performed a stepped exercise intensity cycling protocol on three separate occasions, each consisting of a stepped increase from 55% to 65% peak oxygen consumptionVO_2,peak of 6-min duration, followed by a stepped decrease to 55%VO_2,peak of 10-min duration. This stepped protocol was preceded by either 5, 15, or 60 min of cycling at 55%VO_2,peak. The response times for each variable were calculated at 10% increments between the prestep baselines and poststep plateaux. Following the stepped increase, the response times forVO₂ at the 50%, 60%, 70%, 80%, and 90% relative increments were significantly reduced in the 60-min condition compared to the 15-min condition (P< 0.05); however, the response times forVCO₂ andf _c were not significantly altered across the three conditions. No significant differences were found in the response times forVO₂,VCO₂ andf _c, across the three conditions following the stepped decrease in exercise intensity. It was concluded that the faster response time of aerobic metabolism to a stepped increase in exercise intensity was mediated by increases in active muscle temperature, leading to improved oxygen utilisation.     

The effects of 2,3-butanedione monoxime on initial heat,tension, and aequorin light output of ferret papillary muscles

At low concentrations (up to 5 mM) the compound 2,3-butanedione monoxime (BDM) was found to reduce twitch tension and initial heat production in isolated papillary muscles without significantly affecting the size of the intracellular Ca transient measured with aequorin luminescence. Higher concentrations of BDM caused further inhibition of twitch tension and heat production with a fall in the size of the Ca⁺ transient. The size of the aequorin transient was 50% of the control value at 15 mM BDM while twitch tension was negligible. These results suggest that BDM selectively inhibits Ca²⁺ activated force in cardiac muscle at low concentrations with additional effects on intracellular calcium at concentrations above 5 mM.     

The effects of brief maternal separations on behavior and heart rate of two week old rat pups

Behavioral and cardiac rate responses to a novel test box were recorded from rat pups separated from their mothers for 18 hr and from littermates allowed to remain with their mothers. If body temperatures of separated pups were maintained at nest levels, they showed increased numbers of rises, squares crossed and head raises but did not differ from their mothered littermates in self-grooming or elimination. If no temperature source was supplied, separated pups lost 3°C and showed generally reduced levels of behavior. Heart rates of separated pups decreased markedly during separation, regardless of whether body temperatures were maintained. The cardiac rate response of mothered pups to the test box was a transient slowing in the first two min. Both separated groups showed acceleratory responses to the test box. Those whose temperatures had been maintained had more prolonged cardiac acceleration which reached levels close to the range of their mothered littermates.     

The effect of centrally administered TRH on blood pressure,heart rate and ventilation in rat

Different doses (3, 16, 80, 400 and 2000 ng per rat) of TRH or alternatively saline were infused into the lateral ventricle of urethane-ahaesthetized rats and blood pressure, heart rate, respiration rate and tidal volume were recorded. A dose of 3 ng TRH caused a significant elevation of blood pressure and heart rate, whereas 16 ng was needed for respiration rate to be elevated. There was no change in respiratory minute volume during the experiment. We conclude that TRH has profound physiological effects and that TRH, given centrally, is a potent hypertensive, chronotropic and tachypnoeic agent.