Performance fatigability during isometric vs. concentric quadriceps fatiguing tasks in men and women

In the present study, we aimed to provide a robust comparison of the fatigability of the knee extensors following isometric (ISO) and concentric (CON) tasks. Twenty young adults (25 ± 4 yr, 10 women) randomly performed the ISO and CON quadriceps intermittent fatigue test, consisting of ten (5 s on/5-s off, ISO) or one-hundred (0.5-s on/0.5-s off, CON) contractions with 10 % increments per stage until exhaustion. Performance fatigability was quantified as maximal isometric (MVIC) and concentric (MVCC) torque loss. Voluntary activation and contractile function (peak-twitch) were investigated using peripheral nerve stimulation. Number of stages (6.2 ± 0.7 vs. 4.9 ± 0.8; P < 0.001) and torque-time integral (20,166 ± 7,821 vs. 11,285 ± 4,933 Nm.s; P < 0.001) were greater for ISO than CON. MVIC, MVCC and voluntary activation decreased similarly between sessions (P > 0.05) whereas peak-twitch amplitude decreased more for CON (P < 0.001). The number of contractions was similar across sexes (ISO: men = 62 ± 8, women = 61 ± 5; CON: men = 521 ± 67, women = 458 ± 76, P > 0.05). MVCC was more reduced in women for both sessions (all P < 0.05), while MVIC loss was similar between sexes. We concluded that, despite greater torque-time integral and duration for ISO, both sessions induced a similar performance fatigability at exhaustion. Contractile function was more altered in CON. Finally, sex-related difference in fatigability depends on the contraction mode used during testing.     

Strength training reduces force fluctuations during anisometric contractions of the quadriceps femoris muscles in old adults.

The greater fluctuations in motor output that are often exhibited by old adults can be reduced with strength training. The purpose of the study was to determine the effect of strength and steadiness training by old adults on fluctuations in force and position during voluntary contractions with the quadriceps femoris muscle. Healthy old adults (65-80 yr) completed 16 wk of heavy-load (80% of maximum, n = 11) strength training, heavy-load steadiness training (n = 6), or no training (n = 9). Steadiness training required subjects to match the angular displacement about the knee joint to a constant-velocity template. The Heavy-Load group experienced a 5.5% increase in muscle volume, a 25% increase in maximal voluntary contraction force, and a 26% increase in the one-repetition (1-RM) load. The Heavy-Load Steady group experienced increases of 11.5, 31, and 36%, respectively. The maximal electromyogram signal of quadriceps femoris increased by 51% in the two training groups. The coefficient of variation (CV) for force during submaximal isometric contractions did not change with training for any group. Although both training groups also experienced a reduction in CV for force during anisometric contractions with a 50% 1-RM load, the standard deviation of position did not change with time for any group. The Heavy-Load Steady group also experienced a reduction in CV for force during the training contractions performed with the 80% 1-RM load. Thus strength training reduced the force fluctuations of the quadriceps femoris muscles during anisometric contractions but not during isometric contractions.     

Changes of the force-frequency relationship in human tibialis anterior at fatigue.

This work estimates the influence of the single twitch (ST) parameters changes on specific regions of the force-frequency relationship (FFR) in fatigued human tibialis anterior (TA). In 20 subjects (age 20-40) the TA underwent three stimulation phases: (a) five STs at 1 Hz followed by 5 s stimulation with increasing rate (1-50 Hz, to obtain FFR); (b) fatiguing stimulation (35 Hz for 40 s); (c) same as in "a". By the average STs (mean of the five responses) of a and c phases, the peak twitch (Pt) was calculated. Moreover, after ST normalization to Pt, the maximum contraction rate (MCR) and the maximum relaxation rate (MRR) were computed. By the FFR, normalized to the 50 Hz force, we first defined the threshold frequency (TF) when the force oscillation presented the same value in (a) and (c), and then the areas below the FFR in the 1 Hz-TF and in the TF-50 Hz ranges. RESULTS: In unfatigued and fatigued muscle Pt, and MRR changed from 6.12 +/- 3.08 to 3.27 +/- 1.16 N and from 0.87 +/- 0.13 to 0.65 +/- 0.09% Pt/ms, respectively. MCR did not change significantly. The 1 Hz-TF area ratio (c/a) was > 1 for muscles having fatigued Pt > 60% of its basal value. The TF-50 Hz area ratio (c/a) was mostly below 1. CONCLUSIONS: At fatigue, MRR reduction, leading to a better fusion of muscle mechanical output, is able to compensate, in the 1 Hz-TF frequency range, up to 40% Pt loss; beyond TF, the changes of FFR are related to the degree of force loss indicated by the fatigued Pt.     

Force-generating capacities and fatigability of the quadriceps femoris in relation to different exercise modes

In this study, we examined whether different exercise modes provoke functional differences in maximal and explosive force-generating capacities and fatigability of the quadriceps femoris (QF). Additionally, the interaction of different functional capacities was studied in competitive athletes. Ten competitive tennis players and 10 endurance athletes participated in the study. Pre-exercise force-generating capacities were determined during maximal voluntary isometric knee extensions (MVC). Fatigability of the QF was studied using sustained isometric contractions with target loads of 20% and 40% of pre-exercise MVC. Postexercise MVCs were conducted 20 seconds, 1 minute, and 3 minutes post task failure. Muscle activation of the QF during the fatiguing exercises and postexercise MVCs was estimated using surface electromyography. Higher explosive force-generating capacities, but no differences in absolute moments, were detected in tennis players compared with endurance athletes. Fatigability of the QF during both fatiguing tasks was approximately the same in both athletic populations. This was indicated by minor group differences in endurance time, postexercise MVC production, and electromyography (EMG)-estimated muscle activation during fatigue. Variability in endurance time was not significantly associated with pre-exercise force-generating capacities in these competitive athletes. In both athletic populations, recovery of MVC was significantly slower after the fatiguing contraction with 20% of MVC compared with that with 40% of MVC. These results may enhance understanding of plasticity of the neuromuscular system and yield interesting information for the optimization of athletic training programs. Explosive strength training might enhance endurance athletes' explosiveness without decreasing muscle fatigue resistance. The exercise profile of competitive tennis is suggested to act as a sufficient trigger to reach high neuromuscular fatigue resistance but may be inadequate to cause significant gains in absolute muscle strength.     

Interspecies differences in the force-frequency relationship of the medial gastrocnemius motor units.

Single, functionally isolated motor units were studied in the medial gastrocnemius (MG) muscle of cats and rats. Axons of their motoneurons were stimulated with trains of pulses at frequencies increasing from 1 to 150 Hz and forces developed by muscle fibers were measured and force-frequency curves were compared between species. The following observations were made: (1) the most steep parts of curves (related to unfused tetani of motor units) begun at lower frequencies of stimulations in all types of feline motor units, (2) for fast motor units, the same relative values of force of unfused tetani were achieved at significantly lower frequencies of stimulations in the cat than in the rat. Twitch time parameters of both species influenced the course of force-frequency curves. It was showed that the contraction times of feline units varied in the wide range (21-81 ms), and these units reached 60% of the maximum force at stimulation frequencies between 10 and 38 Hz. On the other hand, contraction times of rat units ranged from 10 to 34 ms, whereas stimulation frequencies necessary to reach 60% of the maximum force varied considerably, from 12 to 65 Hz. The correlations between the above parameters were found for motor units of each species. However, the regression lines drown for the collected population of cat and rat units did not form linear continuity. Thus it seems that interspecies differences in the twitch contraction times do not fully explain different force-frequency relationships in mammalian skeletal muscles.     

Phospholamban: a major determinant of the cardiac force-frequency relationship

The cardiac force-frequency relationship has been known for over a century, yet its mechanisms have eluded thorough understanding. We investigated the hypothesis that phospholamban, a potent regulator of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), determines the cardiac force-frequency relationship. Isolated left ventricular papillary muscles from wild-type (WT) and phospholamban knockout (KO) mice were stimulated at 2 to 6 Hz. The force-frequency relationship was positive in WT but negative in KO muscles, i.e., it was inverted by ablation of phospholamban (P < 0.01, n = 6 mice). From 2 to 6 Hz, relaxation accelerated considerably (by 10 ms) in WT muscles but only minimally (by 2 ms) in KO muscles (WT vs. KO: P < 0. 0001, n = 6). To show that the lack of frequency potentiation in KO muscles was not explained by the almost maximal basal contractility, twitch duration was prolonged in six KO muscles with the SERCA inhibitor cyclopiazonic acid to WT values. Relaxation still failed to accelerate with increased frequency. In conclusion, our results clearly identify phospholamban as a major determinant of the cardiac force-frequency relationship.     

SERCA2a activity correlates with the force-frequency relationship in human myocardium

The present investigation addresses whether protein expression and function of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) and phospholamban (PLB) correlate in failing and nonfailing human myocardium. SERCA2a activity and protein expression, PLB phosphorylation, and the force-frequency relationship (FFR) have been determined in right atrium (RA) and left ventricle (LV) from nonfailing (NF, n = 12) and terminally failing [dilated cardiomyopathy (DCM), n = 12] human hearts. Only in LV of DCM hearts was SERCA2a activity significantly decreased [maximal turnover rate (V(max)) = 196 +/- 11 and 396 +/- 30 nmol. mg(-1). min(-1) in LV and RA, respectively], whereas protein expression of SERCA2a in the different chambers was unchanged in NF (3.9 +/- 0.3 and 3.2 +/- 0.4 densitometric units in LV and RA, respectively) and DCM hearts (4.8 +/- 0.8 and 3.4 +/- 0.1 densitometric units in LV and RA, respectively). Phosphorylation of PLB was higher in LV than in RA in NF (Ser(16): 180.5 +/- 19.0 vs. 56.8 +/- 6.0 densitometric units; Thr(17): 174.6 +/- 11.2 vs. 37.4 +/- 8.9 densitometric units) and DCM hearts (Ser(16): 132.0 +/- 5.4 vs. 22.4 +/- 3.5 densitometric units; Thr(17): 131.2 +/- 10.9 vs. 9.2 +/- 2.4 densitometric units). SERCA2a function, but not protein expression, correlated well with the functional parameters of the FFR in DCM and NF human hearts. Regulation of SERCA2a function depends on the phosphorylation of PLB at Ser(16) and Thr(17). However, direct SERCA2a regulation might also be affected by an unknown mechanism.     

EMG spectral shift as an indicator of fatigability in an heterogeneous muscle group

Changes in electromyogram (EMG) power spectra were investigated in the triceps surae muscles of two classes of individuals (untrained subjects and athletes) maintaining a plantarflexion torque of 80% of maximal voluntary contraction until exhaustion. A set of 23 parameters describing changes in the frequency content and power of EMG was defined. For most experiments, classical changes were found, indicating a shift of the EMG spectra towards lower frequencies and an increase in the total power of the signals. In 12% of the experiments, alternations in activity between synergistic muscles were found, leading to a large variability in the spectral parameters. After the expression of each experiment in terms of a reduced data matrix and matrix to vector transformations, three methods of discrimination were used to classify subjects with respect to changes in the EMG signal during sustained contraction: (1) evaluation of the most discriminating parameter, (2) principal components analysis, (3) transformation maximizing differences between classes. Method (3) was found to be preferable since it led to good separation of the two classes in a reference group of subjects and a satisfactory projection of each individual from a group of unknowns into the appropriate class. These results suggest using a method such as this for ergonomic or athletic training purposes rather than the usual method of monitoring the frequency shift of the EMG.     

Aging alters the force-frequency relationship and toxicity of oxidative stress in rabbit heart

Adult (6 months) and senescent (greater than 5 years) rabbit atria were studied under conditions known to increase cytoplasmic calcium (increased frequency of contraction and oxidative stress). At a contraction frequency of 1/sec, cardiac relaxation (90% relaxation time) was similar in senescent and adult atria but at a frequency of 2 or 3/sec, relaxation was significantly slower in senescent preparations (P less than 0.05). Additional experiments indicated that H2O2 (500 microM), a powerful oxidant, increased resting force and decreased developed force (DF) much more rapidly in senescent than adult atria; the maximum decrease in DF, however, was less in senescent preparations (adult = 81 +/- 6% and senescent = 42 +/- 27% of pre-H2O2 values; P less than 0.05). Age-related differences in effects of H2O2 did not result simply from a decreased ability of senescent hearts to detoxify an oxidative stress by the glutathione pathway. Both basal glutathione (GSH) concentrations and the H2O2-mediated decreases in GSH were similar in adult and senescent ventricular preparations, as were activities of glutathione peroxidase and glutathione reductase. These observations suggest that interventions known to increase cytoplasmic calcium can amplify age-related impairments of cardiac relaxation through mechanisms that may be independent of the glutathione pathway.     

An evaluation of different protocols for measuring the force-velocity relationship of the human quadriceps muscles

A modified Cybex II isokinetic dynamometer was used to evaluate the problems associated with measuring the concentric force-velocity characteristics of human knee extensor muscles. Three contraction protocols were investigated, simple voluntary contractions (VC); releases from maximal voluntary isometric contractions (VR) and releases from. isometric femoral nerve stimulated contractions (FNR). Percutaneous stimulation of the quadriceps was unsuitable for dynamic contractions as the proportion of the muscle activated varied with the angle of knee flexion. Isometric length-tension relationships and isokinetic contractions at seven angular velocities between 0.5 and 5.2 rad · s^–1 were recorded in five subjects. During isometric and slow dynamic contractions the voluntary forces were often greater than those obtained by femoral nerve stimulation, probably due to subjects stretching the rectus femoris during voluntary manoeuvres. It was found that the VC protocol produced acceptable isokinetic force recordings only at velocities below 3.1 rad · s^–1 in most subjects whilst VR contractions resulted in unexpectedly low forces at velocities below 1.57 rad · s^–1. Of the three techniques employed, FNR, although uncomfortable for subjects, provided the most accurate and reliable method of measuring force-velocity characteristics of knee extensor muscles. FNR contractions produced a force-velocity curve which showed a smooth decline in force with increasing velocity up to 5.2 rad · s^–1. VC contractions appear to be an acceptable alternative for testing the muscles provided the angular velocity is less than 3.1 rad · s^–1 and the subjects can be prevented from stretching the rectus femoris during the movement.     

Age-related changes in neuromuscular function of the quadriceps muscle in physically active adults

Substantial evidence exists for the age-related decline in maximal strength and strength development. Despite the importance of knee extensor strength for physical function and mobility in the elderly, studies focusing on the underlying neuromuscular mechanisms of the quadriceps muscle weakness are limited.The aim of this study was to investigate the contributions of age-related neural and muscular changes in the quadriceps muscle to decreases in isometric maximal voluntary torque (iMVT) and explosive voluntary strength. The interpolated twitch technique and normalized surface electromyography (EMG) signal during iMVT were analyzed to assess changes in neural drive to the muscles of 15 young and 15 elderly volunteers. The maximal rate of torque development as well as rate of torque development, impulse and neuromuscular activation in the early phase of contraction were determined. Spinal excitability was estimated using the H reflex technique. Changes at the muscle level were evaluated by analyzing the contractile properties and lean mass.The age-related decrease in iMVT was accompanied by a decline in voluntary activation and normalized surface EMG amplitude. Mechanical parameters of explosive voluntary strength were reduced while the corresponding muscle activation remained primarily unchanged. The spinal excitability of the vastus medialis was not different while M wave latency was longer. Contractile properties and lean mass were reduced.In conclusion, the age-related decline in iMVT of the quadriceps muscle might be due to a reduced neural drive and changes in skeletal muscle properties. The decrease in explosive voluntary strength seemed to be more affected by muscular than by neural changes.     

Aging affects different human muscles in various ways. An image analysis of the histomorphometric characteristics of fiber types in human masseter and vastus lateralis muscles from young adults and the very old

This study is an attempt to objectively evaluate age-related changes in human muscles by use of histomorphometric methods. Aging in humans induces dramatic transformations in the skeletal muscles but little is known as to whether or not the aging processes per se may affect all muscles equally. In this study aging of two human muscles with different functions, origin and nerve supply is compared. Sections were cut from masseter and vastus lateralis muscles obtained from young adults aged 18-24 years and from the very old aged 90-102 years. Muscle fiber types were classified with the traditional myofibrillar ATPase staining. Various histomorphometric parameters of the different fiber types in human masseter and vastus lateralis muscle sections were obtained by image analyses to evaluate the age-related changes in the muscle fibers. The following variables were calculated: the number of each fiber type per photographed area; the area of each fiber and two indicators for the shape of the muscle fibers. In the aging muscles there was no relative preferential loss of a fiber type. High numbers of intermediate ATPase-stained fibers (IM fibers) were found in some old vastus muscles but were only sporadic in young vastus muscles. However, there was no change in the percentage distribution of intermediate ATPase-stained fibers when young and very old human masseter muscles were compared. Incubation of the sections with antimyosin antibodies showed that the IM fibers in old masseter and old vastus contained different myosin heavy chains. Thus ATPase activity and anti-myosin staining displayed a somewhat different pattern of fiber type distribution. The main changes in the shape and area indicated that type I fibers in the masseter became more circular while in the vastus they decreased significantly in size. The type II fibers in the vastus became very small and deviated significantly from circularity whereas the type II fibers in the masseter only exhibited a decrease in the size of the fibers. Histomorphometric measurements show that aging affects different human muscles in various ways.     

The role of energy substrates in regulation of the force-frequency relationship in the rat myocardium: effect of ambiocor

The effect of ambiocor (15 mg/100 ml), which contains natural substrates of energy metabolism, on the contractility of papillary muscles (PM) of the right ventricle of the rat heart was studied at stimulation frequencies from 0.1 to 3.0 Hz at a temperature of 30 +/- 1 degrees C (n = 7). The effect was recorded 20 min after the addition of the preparation. It was demonstrated that ambiocor causes a significant (about 70%), independent of stimulation frequency, suppression of the amplitude of isometric contractions (negative inotropic effect), which is coupled with an increase in the relative value of the rest potentiation effect (a qualitative index of calcium content in sarcoplasmic reticulum). The influence of the mixture leads to significant alterations in the time parameters of the "contraction-relaxation" cycle: an increase in the duration of latent period; and a decrease in the time to peak tension and half-relaxation time (TR50%). The effect of the mixture is partially reversible. During the washing of the preparation with the control solution, the qualitative indicators of the contractile activity of papillary muscles are substantially improved in comparison with the initial ones. The character of alterations allows one to assume that the effect of ambiocor in the papillary muscles of the rat heart is realized partly through the suppression of the activity of sarcolemmal calcium channels.     

The role of energy substrates in the regulation of force-frequency relationship in the rat myocardium: the influence of ambiocor

The effect of ambiocor (15 mg/100 ml), which contains natural substrates of energy metabolism, on the contractility of papillary muscle of the right ventricle of rat heart was studied at stimulation frequencies from 0.1 to 3.0 Hz at a temperature of 30 ± 1°C (n = 7). The effect was recorded 20 min after the addition of the preparation. It was demonstrated that ambiocor causes a significant (about 70%), independent of stimulation frequency, suppression of the amplitude of isometric contractions (negative inotropic effect), which is coupled with an increase in the relative value of the rest potentiation effect (a qualitative index of calcium content in SR). The influence of the mixture leads to significant alterations in the time parameters of the “contraction-relaxation” cycle: an increase in the duration of latent period; and a decrease in the time to peak tension and half-relaxation time. The effect of the mixture is partially reversible. During washing off the preparation with the control solution, the qualitative indicators of the contractile activity of papillary muscle are substantially improved in comparison with the initial ones. The character of alterations allows one to assume that the effect of ambiocor in the papillary muscle of the rat heart is realized partly through the suppression of the activity of sarcolemmal calcium channels.     

Influence of aging on sex differences in muscle fatigability.

The purpose of this study was to compare time to task failure for a sustained isometric contraction performed at a submaximal intensity with elbow flexor muscles by young and old men and women. Twenty-seven young (14 men and 13 women, 18-35 yr) and 18 old (10 men and 8 women, 65-80 yr) adults sustained an isometric contraction at 20% of maximal voluntary contraction torque until target torque could no longer be achieved for > or = 5 s. Young adults were stronger than old adults (66.8 +/- 17.9 vs. 47.7 +/- 18.1 N x m, P < 0.05), and men were stronger than women (69.8 +/- 17.9 vs. 47.1 +/- 15.3 N x m, P < 0.05), with no interaction between age and sex (P > 0.05). Time to task failure was longer for old than for young adults (22.8 +/- 9.1 vs. 14.4 +/- 7.6 min, P < 0.05) and for young women than for young men (18.3 +/- 8.0 vs. 10.8 +/- 5.2, P < 0.05), but there was no difference between old women and men (21.3 +/- 10.7 and 24.1 +/- 8.0 min, respectively, P > 0.05) or between young women and old adults (P > 0.05). Mean arterial pressure, heart rate, average electromyographic (EMG) activity, and torque fluctuations of elbow flexor muscles increased during the fatiguing contraction (P < 0.05) for all subjects. Rates of increase in mean arterial pressure, heart rate, and torque fluctuations were greater for young men and old adults, with no differences between old men and women (P > 0.05). Similarly, the rate of increase in EMG activity was greater for young men than for the other three groups. EMG bursts were less frequent for old adults (P < 0.05) at the end of the fatiguing contraction, and this was accompanied by reduced fluctuations in torque. Consequently, time to task failure was related to target torque for young, but not old, adults, and differences in task duration were accompanied by parallel changes in the pressor response.     

Elevated pCO2 affects the lactate metabolic shift in CHO cell culture processes

The shift from lactate production to consumption in CHO cell metabolism is a key event during cell culture cultivations and is connected to increased culture longevity and final product titers. However, the mechanisms controlling this metabolic shift are not yet fully understood. Variations in lactate metabolism have been mainly reported to be induced by process pH and availability of substrates like glucose and glutamine. The aim of this study was to investigate the effects of elevated pCO₂ concentrations on the lactate metabolic shift phenomena in CHO cell culture processes. In this publication, we show that at elevated pCO₂ in batch and fed‐batch cultures, the lactate metabolic shift was absent in comparison to control cultures at lower pCO₂ values. Furthermore, through metabolic flux analysis we found a link between the lactate metabolic shift and the ratio of NADH producing and regenerating intracellular pathways. This ratio was mainly affected by a reduced oxidative capacity of cultures at elevated pCO₂. The presented results are especially interesting for large‐scale and perfusion processes where increased pCO₂ concentrations are likely to occur. Our results suggest, that so far unexplained metabolic changes may be connected to increased pCO₂ accumulation in larger scale fermentations. Finally, we propose several mechanisms through which increased pCO₂ might affect the cell metabolism and briefly discuss methods to enable the lactate metabolic shift during cell cultivations.     

Coactivation of the antagonist muscle does not covary with steadiness in old adults.

The purpose of the study was to determine the association between steadiness and activation of the agonist and antagonist muscles during isometric and anisometric contractions. Young (n = 14) and old (n = 15) adults used the first dorsal interosseus muscle to perform constant-force and constant-load tasks (2.5, 5, 20, 50, and 75% maximum) with the left index finger. Steadiness was quantified as the coefficient of variation of force and the SD of acceleration normalized to the load lifted. The old adults were less steady at most target forces with isometric contractions (2.5, 5, and 50%) and with most loads during the anisometric contractions (2.5, 5, and 20%). Furthermore, the old adults were less steady when performing lengthening contractions (up to 50%) compared with shortening contractions, whereas there was no difference for young adults. The reduced steadiness exhibited by the old adults during these tasks was not associated with differences in the average level of agonist muscle electromyogram or with coactivation of the antagonist muscle.     

Action potential duration and force-frequency relationship in isolated rabbit,guinea pig and rat cardiac muscle

The effect of action potential duration and elevated cytosolic sodium concentration on the forcefrequency relationship in isolated rabbit, guinea pig and rat papillary muscle preparations was studied. Shortening of action potential duration in guinea pig and rabbit from 150–200 ms to values characteristic of rat (20–40 ms), using the K_(ATP) channel activator levkromakalim (15 mol·l^–1), markedly reduced the force of contraction and converted the positive force-frequency relationship into negative one at longer pacing cycle lengths. This conversion was greatly enhanced in the presence of acetylstrophanthidin (0.2–1 mol·l^–1), an inhibitor of the Na-K pump. Acetylstrophanthidin (1 mol·l^–1) alone, however, had no effect on the forcefrequency relationship. Prolongation of action potential duration in rat with inhibitors of cardiac K channels (4-aminopyridine [10 mmol·l^–1] plus tetraethylammonium [2 mmol·l^–1) increased the force of contraction and abolished the negative force-frequency relationship observed in rat at longer pacing-cycle lengths. It is concluded that both action potential duration and cytosolic sodium concentration are major determinants of the force-frequency relationship in mammalian myocardium.Abbreviations AC acetylstrophanthidin - APD action potential duration - APD ₅₀ and APD ₉₀ action potential duration measured at 50% and 90% level of repolarization, respectively - SR sarcoplasmic reticulum