Energy liberation and chemical change in frog skeletal muscle during single isometric tetanic contractions

Recent data obtained from Rana temporaria sartorius muscles during an isometric tetanus indicate that the time-course of phosphocreatine (PC) splitting cannot account for the total energy (heat + work) liberation (Gilbert et al. 1971. J. Physiol. (Lond.) 218:)63). As this conclusion is important to an understanding of the chemical energetics of contraction, similar experments were performed on unpoisoned, oxygenated Rana pipiens sartorius muscles. The muscles were tetanized (isometrically) at 0 degrees C for 0.6, 1, or 5 s; metabolism was rapidly arrested by freezing the muscles with a specially designed hammer apparatus, and the frozen muscles were chemically analyzed. Comparable myothermal measurments were made on frogs from the same batch. Results of these experiments indicate: (a) The energy liberation parallels the PC and ATP breakdown with a proportionality constant of 10.7 kcal/mol; (b) comparably designed experiments with sartorius muscles of R. temporaria revealed that the ratio of energy liberation to PC splitting was significantly greater than that observed in R. pipiens sartorius muscles; (c) there is no systematic difference between experiments in which metabolism was arrested by the hammer apparatus and others using a conventional immersion technique.     

Kinetic studies on the initial contraction dependent high ATPase activity of actomyosin molecules

In contracting (superprecipitating) clearing and fully contracted (previously superprecipitated) actomyosin molecules the presteady state phosphate burst was found to be 2 nanomoles inorganic phosphate (Pi) per nanomole myosin. In these muscle models a significant difference in the Mg2+ ATPase activity was found following the initial phosphate burst. Between 120 and 800 milliseconds after the commencement of the reaction the Mg2+ ATPase activity of contracting actomyosin molecules was 5-10 times greater than that of the fully contracted or clearing actomyosin molecules. In the same time interval the rate of turbidity increase of the contracting actomyosin molecules was about 10 fold greater than during the remainder of the time to reach maximal superprecipitation. This high initial ATPase activity found to be present only in the contracting actomyosin molecules and coinciding with the high rate of the velocity of contraction provides sufficient energy for contraction. We propose that this high Mg2+--ATPase activity following the initial burst and included as a part of "conventional" steady state ATPase activity is the source of energy for muscular contraction. Calculation of kinetic and thermodynamic constants indicates that the contracting actomyosin molecule is subjected to a conformational change. As a consequence of contraction the complementarity of the enzyme site to the intermediate complex decreases about 100 fold. Thus the contracted molecules temporarily become relatively refractive to provide energy for the contractile process. In our opinion these findings are important with regard to muscular contraction.     

Energy balance studies in frog skeletal muscles shortening at one-half maximal velocity

High-energy phosphate metabolism and energy liberated as heat and work were measured in 3-s tetani of frog sartorius muscle at 0 degree C. Two contraction periods were studied: (a) a 0.35-s period of shortening near half-maximum velocity beginning after 2 s of isometric stimulation, and (b) a 0.65-s isometric period immediately following the shortening. There were no significant changes in levels of ATP, ADP, or AMP in the two contraction periods. The observed changes in inorganic phosphate and creatine levels indicated that the only significant reaction occurring was phosphocreatine splitting. The mean rate of high-energy phosphate splitting during the shortening, 1.60 +/- 0.23 mumol X g-1 X s-1 (n = 24), was about fivefold higher than that in the 1-s period in the isometric tetanus, 0.32 +/- 0.11 mumol X g-1 X s- 1 (n = 17), observed in our previous study. The mean rate in the post- shortening period, 0.46 +/- 0.13 mumol X g-1 X s-1 (n = 17), was not significantly different from that in the 1-s period in the isometric tetanus. A large amount of heat plus work was produced during the shortening period, and this could be accounted for by simultaneous chemical changes. In the post-shortening period, the observed enthalpy was also accounted for by simultaneous chemical reactions. Thus, the present result is in sharp contrast to that obtained from a similar study performed at a shortening at Vmax, where an enthalpy excess was produced during shortening and an enthalpy deficit was produced during the period following the shortening.     

THE EXCRETION OF CARBON DIOXIDE BY RELAXED AND CONTRACTED SEA ANEMONES

1. The metabolism of the sea anemone Metridium marginatum Edw. was measured in four states, relaxed, relaxing, contracted, and contracting, by means of an Osterhout respiratory apparatus. The basis of measurement was the number of hundred-thousandths of a milligram of carbon dioxide excreted per second by a gram of living sea anemone. 2. In the relaxed state this varied from 6.1 to 4.4+ and averaged 5.43–. 3. In a comparison of the relaxed and contracted states the amount of carbon dioxide excreted was found to beabout the same; in one instance in relaxation 4.2 and in contraction 4.1+; in another in relaxation 7.8+ and 7.9– and in contraction 8.1–. 4. In a comparison of the three states relaxed, relaxing, and contracting, the first two were found to average about the same, 4.8+ and 4.6– respectively and the last proved to be appreciably higher 7.1–. 5. It is, therefore, concluded that the process of relaxing and the states of relaxation and of contraction are accompanied by no unusual metabolism, but that in the operation of contracting the metabolism becomes about half again as intense as that characteristic of the other states. 6. The maintenance of the contracted state in Metridium for days at a time without an increase of metabolism indicates that its musculature is of the type known as tonus muscle. 7. In tonus muscle, contraction is accomplished by an active shortening of the myofibrils, extension by a passive drawing out of these fibrils through the distension of the adjacent cavities, etc., and the continued maintenance of any particular state of shortening by some form of catch mechanism in the muscle, such, possibly, as the gelation of its sarcoplasm.     

Mechanical work as predictor of force enhancement and force depression

The steady-state force following active muscle shortening or stretch differs from the maximum isometric force associated with the final length. This phenomenon proves that the isometric force production is not only dependent on current muscle length and length time derivative, but depends on the preceding contraction history. Isolated extensor digitorum longus and soleus muscles from mice (NMRI strain) were used to investigate the force produced by a muscle, and some parameters hypothetically influencing this history-dependent force modification. The muscles were pre-stimulated at a fixed length, then different stretch/shortening episodes were introduced, whereafter changes of the active force were recorded while the muscles were held isometrically to approach a steady-state force before de-stimulation. The mechanical work during active stretch and shortening was evaluated by integrating the product of force and ramp velocity over the length-varying period. The results show a negative linear correlation between the force modification and the mechanical work produced on or by the muscle, continuous between shortening and stretch. A corresponding modification of the passive force component following each stimulation was also observed. The conclusion is that the isometric force attained after stretch or shortening is well described by an asymptotic force which is determined by the mechanical work.     

Evidence for increased low force cross-bridge population in shortening skinned skeletal muscle fibers: implications for actomyosin kinetics.

The dynamic characteristics of the low force myosin cross-bridges were determined in fully calcium-activated skinned rabbit psoas muscle fibers shortening under constant loads (0.04-0.7 x full isometric tension Po). The shortening was interrupted at various times by a ramp stretch (duration, 10 ms; amplitude, up to 1.8% fiber length) and the resulting tension response was recorded. Except for the earlier period of velocity transients, the tension response showed nonlinear dependence on stretch amplitude; i.e., the magnitude of the tension response started to rise disproportionately as the stretch exceeded a critical amplitude, as in the presence of inorganic phosphate (Pi). This result, as well as the result of stiffness measurement, suggests that the low force cross-bridges similar to those observed in the presence of Pi (presumably A.M.ADP.Pi) are significantly populated during shortening. The critical amplitude of the shortening fibers was greater than that of isometrically contracting fibers, suggesting that the low force cross-bridges are more negatively strained during shortening. As the load was reduced from 0.3 to 0.04 P0, the shortening velocity increased more than twofold, but the amount of the negative strain stayed remarkably constant (approximately 3 nm). This This insensitiveness of the negative strain to velocity is best explained if the dissociation of the low force cross-bridges is accelerated approximately in proportion to velocity. Along with previous reports, the results suggest that the actomyosin ATPase cycle in muscle fibers has at least two key reaction steps in which rate constants are sensitively regulated by shortening velocity and that one of them is the dissociation of the low force A.M.ADP.Pi cross-bridges. This step may virtually limit the rate of actomyosin ATPase turnover and help increase efficiency in fibers shortening at high velocities.     

Energy metabolism in relation to oxygen supply in contracting rat skeletal muscle

The regulation of the energy metabolism in contracting skeletal muscle is under close control, and several regulating factors have been reported. The aim of this study was to investigate the importance of the oxygen supply as a limiting factor for muscle performance during contractions and recovery from contractions. To perform well-controlled standardized experiments on contracting skeletal muscle, the perfused rat hind limb model was developed. The 31P NMR technique was adapted to the rat hind limb model. This enabled continuous nondestructive monitoring of the energy state at various levels of muscular activity. Significant correlations were found between oxygen delivery and oxygen consumption, lactate release, and glucose uptake, respectively. An increased degree of fatigue was observed at lower oxygen deliveries. In both soleus and gastrocnemius muscles, oxygen delivery correlated with the intramuscular concentrations of phosphocreatine (PCr), lactate, and glycogen. The 31P NMR experiments showed a correlation between oxygen delivery and the steady-state level of PCr/inorganic phosphate (Pi) during the contraction period. The rate of recovery in PCr/Pi after the contraction was also dependent on oxygen delivery. The results demonstrate a causal relationship between oxygen supply and energy state in contracting as well as recovering skeletal muscles.     

Tension-time index, fatigue, and energetics in isolated rat diaphragm: a new experimental model.

The tension-time index (TTI) has been used to estimate mechanical load, energy utilization, blood flow, and susceptibility to fatigue in contracting muscle. The TTI can be defined, for a rhythmically contracting muscle, as the product of average force development divided by maximum tetanic force times duty cycle [contraction time / (contraction + relaxation time)]. In this study, the TTI concept was applied to isolated diaphragm via a method that allowed TTI to be clamped at a predetermined value. The hypothesis tested was that, at constant TTI, muscle energetics and the extent of fatigue would vary with stimulation frequency. Isolated diaphragm strips were stimulated at 25, 50, 75, or 100 Hz for 4 min, one per second. Duty cycle was continuously adjusted to maintain TTI at 0.07, which was near the highest TTI tolerated for 4 min, at 20-Hz stimulation. At the end of the fatigue run, muscles were either immediately frozen for determination ATP, creatine, and creatine phosphate concentrations (n = 6) or stimulated for evaluation of low- and high-frequency fatigue (n = 5). Results demonstrated no difference in the extent of fatigue or in the final ATP and creatine phosphate concentrations between groups. Large within-run increases in duty cycle were required at low stimulation frequencies, but only small increases were required at the highest frequencies. The results demonstrate that, at a constant TTI, similar fatigue properties predominate at all stimulation frequencies with no clear distinction between high- and low-frequency fatigue. The method of clamping TTI during fatigue may be useful for evaluating energetics and contractile function between treatment groups in isolated muscle when treatment influences baseline contractile characteristics.     

Myosin light chain phosphorylation during contraction of chicken fast and slow skeletal muscles

A modified automatic freezing apparatus (K. M. Kretzschmar and D. R. Wilkie, 1962, J. Physiol. (London), 202, 66–67) was used for studying light chain phosphorylation during the early phase of contraction of the fast, posterior latissimus dorsi, and slow, anterior latissimus dorsi, muscles of chicken at 37 °C. The frozen muscles were worked up under conditions which avoid artifacts in quantitating the level of light chain phosphorylation in contracting and resting muscles. The posterior latissimus dorsi muscle reached 80% of its maximal isometric tension at 0.1 s of tetanic stimulation. At the same time, light chain phosphorylation increased by 60% of its maximal extent. The peak tension of the posterior muscle at 0.2 s of stimulation was accompanied by maximal light chain phosphorylation. In case of the slow anterior latissimus dorsi muscle, maximal tetanic tension was developed in 2.5 – 5 s and light chain phosphorylation also proceeded at a much slower rate than in the fast posterior muscle. When contralateral posterior latissimus dorsi muscles were stimulated for 0.2 s and one muscle was frozen at the height of tetanus while the other muscle was allowed to relax and frozen 0.4 s after terminating the stimulation, both contracted and relaxed muscles exhibited maximal light chain phosphorylation. However, when the muscle was allowed to relax for 0.8 s before freezing, half of the phosphorylated light chain became dephosphorylated. The resting level of phosphate content of the light chain was restored in both the posterior and anterior muscles during a longer time after relaxation.     

Relationship between reaction time of eye movement and activity of the neck extensors

This study investigated the relationship between the reaction time of eye movement (RTEM) and activity of the superficial neck extensor muscles when the shoulder girdle elevator muscles contracted isometrically. The results were compared with those of a previous study in which the subjects's head was fixed and loaded with the neck flexed. When the shoulder girdle elevator muscles contracted isometrically, RTEM decreased significantly in comparison to RTEM at rest. This demonstrated that the reaction time significantly decreased not only as a result of the neck in flexion, which activated the deep and superficial neck extensor muscles, but also from contraction of the shoulder girdle elevator muscles which mainly activated the superficial extensor muscles. The relationship between RTEM and relative muscle load of the shoulder girdle elevator muscles showed that RTEM decreased up to 30% loading, and with loading above 40% the RTEM was longer than with 30%. The relative muscle load for the shortest RTEM demonstrated a subject-to-subject variance ranging from 24.7% to 49.6%. The difference between RTEM at rest and at their shortest reaction time was approximately 20 ms, which was consistent with the data for the neck in flexion. However, the relative muscle load for the shortest RTEM differed between the current and previous studies. The parameters obtained in this study were higher than for those in the previous study.     

The weak link: do muscle properties determine locomotor performance in frogs?

Muscles power movement, yet the conceptual link between muscle performance and locomotor performance is poorly developed. Frog jumping provides an ideal system to probe the relationship between muscle capacity and locomotor performance, because a jump is a single discrete event and mechanical power output is a critical determinant of jump distance. We tested the hypothesis that interspecific variation in jump performance could be explained by variability in available muscle power. We used force plate ergometry to measure power produced during jumping in Cuban tree frogs (Osteopilus septentrionalis), leopard frogs (Rana pipiens) and cane toads (Bufo marinus). We also measured peak isotonic power output in isolated plantaris muscles for each species. As expected, jump performance varied widely. Osteopilus septentrionalis developed peak power outputs of 1047.0 ± 119.7 W kg(-1) hindlimb muscle mass, about five times that of B. marinus (198.5 ± 54.5 W kg(-1)). Values for R. pipiens were intermediate (543.9 ± 96.2 W kg(-1)). These differences in jump power were not matched by differences in available muscle power, which were 312.7 ± 28.9, 321.8 ± 48.5 and 262.8 ± 23.2 W kg(-1) muscle mass for O. septentrionalis, R. pipiens and B. marinus, respectively. The lack of correlation between available muscle power and jump power suggests that non-muscular mechanisms (e.g. elastic energy storage) can obscure the link between muscle mechanical performance and locomotor performance.     

The mechanochemistry of cardiac muscle. I. The isometric contraction

The utilization of creatine phosphate (CP) and adenosine triphosphate (ATP) was studied in the iodoacetate (IAA) and nitrogen (N₂)-treated cat papillary muscle. Under these conditions the net production of ATP does not occur, and the net utilization of ATP is reflected in a fall in CP concentration. The rate of energy utilization of the IAA-N₂-treated cat papillary muscle resting without tension was 0.68 µmole CP/g/min. This rate was increased to 1.07 µmole/g/min when muscles were passively stretched with 2 g of tension. In a series of isometrically contracting muscles CP utilization was found to be proportional to the number of activations and the summated contractile element work. These rates of CP utilization were 0.083 µmole/g/activation and 0.0059 µmole/g-cm of work. The calculated mechanochemical coupling efficiency was 33%.     

The integrated function of muscles and tendons during locomotion

The mechanical roles of tendon and muscle contractile elements during locomotion are often considered independently, but functionally they are tightly integrated. Tendons can enhance muscle performance for a wide range of locomotor activities because muscle-tendon units shorten and lengthen at velocities that would be mechanically unfavorable for muscle fibers functioning alone. During activities that require little net mechanical power output, such as steady-speed running, tendons reduce muscular work by storing and recovering cyclic changes in the mechanical energy of the body. Tendon stretch and recoil not only reduces muscular work, but also allows muscle fibers to operate nearly isometrically, where, due to the force-velocity relation, skeletal muscle fibers develop high forces. Elastic energy storage and recovery in tendons may also provide a key mechanism to enable individual muscles to alter their mechanical function, from isometric force-producers during steady speed running to actively shortening power-producers during high-power activities like acceleration or uphill running. Evidence from studies of muscle contraction and limb dynamics in turkeys suggests that during running accelerations work is transferred directly from muscle to tendon as tendon stretch early in the step is powered by muscle shortening. The energy stored in the tendon is later released to help power the increase in energy of the body. These tendon length changes redistribute muscle power, enabling contractile elements to shorten at relatively constant velocities and power outputs, independent of the pattern of flexion/extension at a joint. Tendon elastic energy storage and recovery extends the functional range of muscles by uncoupling the pattern of muscle fiber shortening from the pattern of movement of the body.     

Variation of muscle stiffness with force at increasing speeds of shortening

Single frog skeletal muscle fibers were attached to a servo motor and force transducer by knotting the tendons to pieces of wire at the fiber insertions. Small amplitude, high frequency sinusoidal length changes were then applied during tetani while fibers contracted both isometrically and isotonically at various constant velocities. The amplitude of the resulting force oscillation provides a relative measure of muscle stiffness. It is shown from an analysis of the transient force responses observed after sudden changes in muscle length applied both at full and reduced overlap and during the rising phase of short tetani that these responses can be explained on the basis of varying numbers of cross bridges attached at the time of the length step. Therefore, the stiffness measured by the high frequency length oscillation method is taken to be directly proportional to the number of cross bridges attached to thin filament sites. It is found that muscle stiffness measured in this way falls with increasing shortening velocity, but not as rapidly as the force. The results suggest that at the maximum velocity of shortening, when the external force is zero, muscle stiffness is still substantial. The findings are interpreted in terms of a specific model for muscle contraction in which the maximum velocity of shortening under zero external load arises when a force balance is attained between attached cross bridges some of which are aiding and others opposing shortening. Other interpretations of these results are also discussed.     

Effects of altering carbohydrate metabolism on energy status and contractile function of vascular smooth muscle

Substrate-dependent changes in vascular smooth muscle energy metabolism and contractile function were investigated in isolated porcine carotid arteries. In media containing glucose glycogen catabolism accounted for all the estimated high-energy phosphate turnover that occurred in conjunction with contraction induced by 80 mM KCl. However, in glucose-free media glycogen catabolism accounted for only a portion of the estimated ATP utilization in resting and contracting arteries, even though glycogen stores were not depleted. The glycogenolysis and lactate production that ordinarily accompanies contraction was completely inhibited by 5 mM 2-deoxyglucose (2-DG). However, there was no decrease in the high-energy phosphate levels when compared to control resting arteries similarly treated with 2-DG. The results suggest that an endogenous non-carbohydrate source may be an important substrate for energy metabolism. Treatment of arteries with 50 microM iodoacetate (IA) in media containing glucose resulted in a marked reduction of high energy phosphate levels and an accumulation of phosphorylated glycolytic intermediates, as demonstrated by 31P-NMR spectroscopy. In glucose-free media, 50 microM IA had only a slight effect on high-energy phosphate levels, while glycogenolysis proceeded unhindered. With 1 mM IA in glucose-free media, the oxidative metabolism of glycogen was inhibited as evidenced by the depletion of high-energy phosphates and the appearance of sugar phosphates in the 31P-NMR spectra. Thus, the titration of enzyme systems with IA reveals a structural partitioning of carbohydrate metabolism, as suggested by previous studies.     

Costal and crural diaphragm in early inspiration: free breathing and occlusion

Changes in length of costal and crural segments of the canine diaphragm were measured by sonomicrometry within the first 100-300 ms of inspiration during CO2 rebreathing in anesthetized animals. Both segments showed small but significant decreases in end-expiratory length during progressive hypercapnia. Although both costal and crural segments showed electromyographic activity within the first 100 ms of inspiration, in early inspiration crural shortening predominated with minimal costal shortening. Neither segment contracted isometrically early in inspiration in the presence of airway occlusion. The amount of crural shortening during airway occlusion exceeded costal shortening; both segments showed increased shortening with prolonged occlusion and increasing CO2. Costal and crural shortening at 100 ms was not different for unoccluded and occluded states. These observations suggest that neural control patterns evoke discrete and unequal contributions from the diaphragmatic segments at the beginning of an inspiration; the crural segment may be predominately recruited in early inspiration. Despite traditional assumptions about occlusion pressure measurement (P0.1), diaphragm segments do not contract isometrically during early inspiratory effort against an occluded airway.     

The effect of cold on adrenergic neurotransmission in canine saphenous arteries and veins

The effect of severe cold (5 to 10 degrees C) on adrenergic neurotransmission was compared in the isolated cutaneous (saphenous) artery and vein of the dog. The vein contracted to sympathetic nerve stimulation at temperatures as low as 10 degrees C; higher temperatures were needed for the artery to contract. Both blood vessels contracted to exogenous norepinephrine at temperatures as low as 5 degrees C. However, the contractile response to exogenous norepinephrine was less in the saphenous artery, and contractions to high K+ solution were depressed by cooling more in the artery than in the vein. During electrical stimulation of the sympathetic nerves in saphenous arteries and veins previously incubated with labeled norepinephrine, progressive cooling from 37 to 5 degrees C caused a sharp decline in overflow of [3H]norepinephrine and its metabolites. However, overflow of labeled norepinephrine in both blood vessels continued at very cold temperatures. Thus the inability of the saphenous artery to contract to sympathetic nerve stimulation at 10 degrees C can be explained by a greater sensitivity of the arterial smooth muscle to the direct depressant effect of cold, rather than to a differential release or metabolism or norepinephrine in the arterial wall or a loss of responsiveness to norepinephrine at very cold temperatures.     

Free radicals may contribute to oxidative skeletal muscle fatigue

We used mouse soleus in vitro (n = 30) and canine gastrocnemius-plantaris preparations (n = 20) pump-perfused at the animal's blood pressure to establish if free radicals contribute to fatigue in oxidative skeletal muscle. The soleus from each leg contracted for 200 ms (70 Hz) once every minute for 60 min in Hepes buffer gassed with 100% oxygen at 27 degrees C. When contracting in Hepes alone, both muscles fatigued at 0.9 mN/mm2.min over the 60 min. The addition of purines to the bath increased the rate to 1.4 mN/mm2.min and the addition of xanthine oxidase to generate free radicals increased the rate again to 1.9 mN/mm2.min. Thus free radicals appeared to attenuate oxidative skeletal muscle function. Each canine muscle contracted isometrically at 4 Hz for 30 min and then rested for 45 min before contracting for a second 30 min at 4 Hz. In each experiment, we infused saline at 0.76 mL/min into resting muscle and at 1.91 mL/min during the first contraction period. During the remainder of the experiment, we infused, at the same rates, saline (n = 4), 10 microM dimethyl sulfoxide (DMSO) (n = 4) to identify the effect of scavenging hydroxyl radicals, 1 mM allopurinol to establish the effect of blocking xanthine oxidase (n = 4), or 200 microM desferoxamine to determine the effect of chelating iron (n = 4). With saline, the fatigue rate over the 30 min of contractions increased from 5.0 +/- 0.2 to 6.3 +/- 0.5 N/kg.min from the first to the second stimulation period. The fatigue rate was slower in the second period with each of the three experimental substances (DMSO, 5.9 +/- 0.8 to 3.2 +/- 0.3; allopurinol, 7.3 +/- 1.1 to 4.6 +/- 0.6; desferoxamine, 6.8 +/- 0.8 to 4.4 +/- 0.8 N/kg.min). The fatigue rate was the same as control when DMSO was infused only during the second contraction period. Therefore, free radicals appeared to contribute to fatigue in oxidative skeletal muscle.     

Alkylacetylglycerophosphocholine stimulates Na+-Ca2+ exchange, protein phosphorylation and polyphosphoinositide turnover in rat ileal plasmalemmal vesicles

The novel ether phospholipid, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC), isometrically contracted helically cut rat ileal smooth muscle strips in a dose- and time-dependent manner. Utilizing an enriched plasma membrane vesicular preparation from rat ileal longitudinal smooth muscle, AGEPC specifically stimulated Na+-Ca2+ exchange in a dose- and time-dependent manner. Concomitant with the AGEPC stimulation of Na+-dependent Ca2+ influx in plasma membrane vesicles is an enhanced turnover of the polyphosphoinositides, an elevated concentration of phosphatidic acid and also an enhanced phosphorylation of an Mr 40,000 plasmalemmal protein. The mechanisms by which AGEPC may regulate ileal plasmalemmal Ca2+ flux and contractility are considered.     

The Anrep effect: an intrinsic myocardial mechanism

In cat papillary muscles contracting physiologically, increasing the afterload caused a biphasic change in contractility. In response to an increase in afterload, contractility (as measured by peak shortening, peak developed force, or peak dF/dt) initially decreased (antihomeometric autoregulation) over the first few beats and then increased slowly with t 1/2 of about 3 min at 30 degrees C and about 1 min at 37 degrees C (homeometric autoregulation). The antihomeometric autoregulation is due to decreased active shortening when the afterload is increased, since it also occurs in response to increased afterload in isotonic contractions. The secondary slow increase in contractility is primarily due to the increase in mean diastolic length that occurs as a result of increased afterload. The time course and the magnitude of the biphasic change in contractility are very similar to those observed in response to afterload increase in intact hearts; we suggest that the secondary slow increase in contractility that we observed is a contributory mechanism to homeometric autoregulation (or the Anrep effect), as it is observed in the whole heart.