Two groups of biochemical reactions underlie muscle contraction: those that consume high-energy phosphates, called initial reactions, and those that regenerate high-energy phosphates, called recovery reactions. Muscular efficiency is the ratio of mechanical work produced to the metabolic energy consumed in the production of that work. The energy consumption term can either incorporate just the initial energy costs, giving the initial mechanical efficiency (eI), or can encompass the net energy cost (the energetic equivalent of the oxygen consumed), giving the net mechanical efficiency (eN). eI is of interest because it provides insights into the fundamental mechanism of energy conversion by myosin cross-bridges.The efficiency of mechanical work generation by crossbridges in cardiac muscle is poorly established because it is difficult to experimentally separate the initial and recovery energy costs. The kinetics of recovery metabolism in cardiac muscle are so rapid that even the energy used within the time course of a single twitch includes a significant recovery metabolism component (Gibbs et al., 1967;. Peterson and Alpert (1991) subtracted the presumed recovery heat component from the energy output recorded during isotonic shortening of rabbit papillary muscles and concluded that the maximum eI in rabbit papillary muscles was 65%. This value is high compared with an estimate based on reported values of eN. eN of isolated cardiac muscle is typically~1 5% (Gibbs et al., 1967;Syme, 1994;. The magnitude of the net metabolic cost of a series of contractions is typically twice that of initial metabolism (e.g. ) so eI should bẽ 2-fold greater than eN; that is, about 30%. Both the approaches described above for determining eI contain elements of uncertainty. For example, Peterson and Alpert (1991) implicitly assumed that the energy output associated with shortening was synchronous with shortening, but, at least in isometric contractions, a substantial fraction of the initial energy output associated with a single twitch appears late in the contraction, during force relaxation . To estimate eI from eN, it must be assumed that the ratio of energy output from recovery processes (R) to energy output from initial processes (I) is the same in isometric contractions and contractions with shortening because the R:I ratio in cardiac muscle has only been measured using isometric contractions . Although it seems reasonable to assume that the R:I ratio is independent of contraction type, the only published comparison of the R:I ratio in isometric and working contractions, which was made using mouse skeletal muscle (Woledge and Yin, 1989), revealed that the ratio was greater in shortening contractions (1.25) than in isometric contractions (1.0). It seems unlikely that such an effect could underlie the combination of eI=65% and eN=15% in cardiac muscle, because this would require the R:I ratio in working The aim of this study was to determine whether the initial mechanical efficiency (ratio of work output to initial metabolic cost) ...

1. Pyruvate has been shown to enhance the contractile performance of cardiac muscle when provided as an alternative substrate to glucose. The aims of the present study were to determine whether the inotropic effects of pyruvate are due to increased mobilization of intracellular Ca2+ ([Ca2+]i) and to compare the effects of pyruvate on [Ca2+]i levels in myocytes from normal and diabetic animals. 2. Fura-2 was used to monitor [Ca2+]i in ventricular myocytes isolated from control and streptozotocin-treated male Wistar rats. The experiments were performed at 25 degrees C, with an extracellular [Ca2+] of 1.5 mmol/L and either 10 mmol/L glucose or 10 mmol/L pyruvate as the substrate. 3. In myocytes from both control and diabetic rats, increasing the stimulus frequency from 0.33 to 2.0 Hz resulted in significant increases in resting and peak [Ca2+]i as well as in the amplitude of the [Ca2+]i transient, irrespective of substrate. Compared with glucose, pyruvate significantly increased resting and peak [Ca2+]i and the amplitude of the [Ca2+]i transient at each stimulus frequency in myocytes from both control and diabetic animals. However, the extent of potentiation of the [Ca2+]i transient amplitude produced by pyruvate was significantly less in myocytes from the diabetic rats. 4. The rate of restitution of the [Ca2+]i transient was used as an index of the rate of Ca2+ cycling by the sarcoplasmic reticulum (SR). Pyruvate enhanced the rate of restitution in control but not diabetic rat cells. 5. The time course of decay of the [Ca2+]i transient was analysed as a measure of the rate of removal of Ca2+ from the cytosol. Pyruvate tended to increase the rate of decay in cells from control but not diabetic animals. The rate of decay was slower in cells from diabetic animals compared with controls. 6. The data reveal that pyruvate increases SR Ca2+ cycling, leading to greater Ca2+ release and an increase in the amplitude of the [Ca2+]i transient. Therefore, it seems highly likely that increased [Ca2+]i mobilization is responsible for the previously reported positive inotropic actions of pyruvate. These effects of pyruvate are attenuated in diabetic rat cells, which may reflect an impaired capacity of mitochondria in diabetic hearts to oxidize pyruvate, thus limiting potential energetic benefits.

The results of previous studies suggest that the maximum mechanical efficiency of rat papillary muscles is lower during a contraction protocol involving sinusoidal length changes than during one involving afterloaded isotonic contractions. The aim of this study was to compare directly the efficiency of isolated rat papillary muscle preparations in isotonic and sinusoidal contraction protocols. Experiments were performed in vitro (27 degrees C) using left ventricular papillary muscles from adult rats. Each preparation performed three contraction protocols: (i) low-frequency afterloaded isotonic contractions (10 twitches at 0.2 Hz), (ii) sinusoidal length change contractions with phasic stimulation (40 twitches at 2 Hz) and (iii) high-frequency afterloaded isotonic contractions (40 twitches at 2 Hz). The first two protocols resembled those used in previous studies and the third combined the characteristics of the first two. The parameters for each protocol were adjusted to those that gave maximum efficiency. For the afterloaded isotonic protocols, the afterload was set to 0.3 of the maximum developed force. The sinusoidal length change protocol incorporated a cycle amplitude of +/−5 % resting length and a stimulus phase of −10 degrees. Measurements of force output, muscle length change and muscle temperature change were used to calculate the work and heat produced during and after each protocol. Net mechanical efficiency was defined as the proportion of the energy (enthalpy) liberated by the muscle that appeared as work. The efficiency in the low-frequency, isotonic contraction protocol was 21.1+/−1.4 % (mean +/− s.e.m., N=6) and that in the sinusoidal protocol was 13.2+/−0.7 %, consistent with previous results. This difference was not due to the higher frequency or greater number of twitches because efficiency in the high-frequency, isotonic protocol was 21.5+/−1.0 %. Although these results apparently confirm that efficiency is protocol-dependent, additional experiments designed to measure work output unambiguously indicated that the method used to calculate work output in isotonic contractions overestimated actual work output. When net work output, which excludes work done by parallel elastic elements, rather than total work output was used to determine efficiency in afterloaded isotonic contractions, efficiency was similar to that for sinusoidal contractions. The maximum net mechanical efficiency of rat papillary muscles performing afterloaded isotonic or sinusoidal length change contractions was between 10 and 15 %.

SUMMARYStudies of cardiac muscle energetics have traditionally used contraction protocols with strain patterns that bear little resemblance to those observed in vivo. This study aimed to develop a realistic strain protocol, based on published in situ measurements of contracting papillary muscles, for use with isolated preparations. The protocol included the three phases observed in intact papillary muscles: an initial isometric phase followed by isovelocity shortening and re-lengthening phases. Realistic papillary muscle dynamics were simulated in vitro (27°C) using preparations isolated from the left ventricle of adult male rats. The standard contraction protocol consisted of 40 twitches at a contraction rate of 2 Hz. Force, changes in muscle length and changes in muscle temperature were measured simultaneously. To quantify the energetic costs of contraction, work output and enthalpy output were determined, from which the maximum net mechanical efficiency could be calculated. The most notable result from these experiments was the constancy of enthalpy output per twitch, or energy cost, despite the various alterations made to the protocol. Changes in mechanical efficiency, therefore, generally reflected changes in work output per twitch. The variable that affected work output per twitch to the greatest extent was the amplitude of shortening, while changes in the duration of the initial isometric phase had little effect. Decreasing the duration of the shortening phase increased work output per twitch without altering enthalpy output per twitch. Increasing the contraction frequency from 2 to 3 Hz resulted in slight decreases in the work output per twitch and in efficiency. Using this realistic strain protocol, the maximum net mechanical efficiency of rat papillary muscles was approximately 15 %. The protocol was modified to incorporate an isometric relaxation period, thus allowing the model to simulate the main mechanical features of ventricular function.

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