An innovative work-loop calorimeter for in vitro measurement of the mechanics and energetics of working cardiac trabeculae

2011 ◽  
Vol 111 (6) ◽  
pp. 1798-1803 ◽  
Author(s):  
Andrew J. Taberner ◽  
June-Chiew Han ◽  
Denis S. Loiselle ◽  
Paul M. F. Nielsen

We describe a unique work-loop calorimeter with which we can measure, simultaneously, the rate of heat production and force-length work output of isolated cardiac trabeculae. The mechanics of the force-length work-loop contraction mimic those of the pressure-volume work-loops experienced by the heart. Within the measurement chamber of a flow-through microcalorimeter, a trabecula is electrically stimulated to respond, under software control, in one of three modes: fixed-end, isometric, or isotonic. In each mode, software controls the position of a linear motor, with feedback from muscle force, to adjust muscle length in the desired temporal sequence. In the case of a work-loop contraction, the software achieves seamless transitions between phases of length control (isometric contraction, isometric relaxation, and restoration of resting muscle length) and force control (isotonic shortening). The area enclosed by the resulting force-length loop represents the work done by the trabecula. The change of enthalpy expended by the muscle is given by the sum of the work term and the associated amount of evolved heat. With these simultaneous measurements, we provide the first estimation of suprabasal, net mechanical efficiency (ratio of work to change of enthalpy) of mammalian cardiac trabeculae. The maximum efficiency is at the vicinity of 12%.

1995 ◽  
Vol 198 (10) ◽  
pp. 2221-2227 ◽  
Author(s):  
D A Syme ◽  
R K Josephson

The work capacity of segments of atrial and ventricular muscle from the frog Rana pipiens was measured as a function of muscle length using the work loop technique. Both the work done during shortening and the work required to re-lengthen the muscle after shortening increased with muscle length. Net work increased with length up to a maximum, beyond which work declined. The optimum sarcomere length for work output was 2.5-2.6 microns for both atrial and ventricular muscle. Isometric force increased with muscle length to lengths well beyond the optimum for work output. Thus, the decline in work at long lengths is not simply a consequence of a reduction in the capacity of heart muscle to generate force. It is proposed that it is the non-linear increase in work required to re-lengthen muscle with increasing muscle length which limits net work output and leads to a maximum in the relationship between net work and muscle length. Extension of the results from muscle strips to intact hearts suggests that the work required to fill the ventricle exceeds that available from atrial muscle at all but rather short ventricular muscle lengths.


2009 ◽  
Vol 107 (3) ◽  
pp. 946-951 ◽  
Author(s):  
June-Chiew Han ◽  
Andrew J. Taberner ◽  
Robert S. Kirton ◽  
Poul M. Nielsen ◽  
Nicholas P. Smith ◽  
...  

To study cardiac muscle energetics quantitatively, it is of paramount importance to measure, simultaneously, mechanical and thermal performance. Ideally, this should be achieved under conditions that minimize the risk of tissue anoxia, especially under high rates of energy expenditure. In vitro, this consideration necessitates the use of preparations of small radial dimensions. To that end, we have constructed a unique micromechanocalorimeter, consisting of an open-ended flow-through microcalorimeter, a force transducer, and a pair of muscle-length actuators. The device enables the metabolic and mechanical performance of cardiac trabeculae carneae to be investigated for prolonged periods in a continuously replenished oxygen- and nutrient-rich environment.


2001 ◽  
Vol 204 (21) ◽  
pp. 3765-3777
Author(s):  
L. J. Mellors ◽  
C. J. Barclay

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.


2000 ◽  
Vol 278 (5) ◽  
pp. H1545-H1554 ◽  
Author(s):  
J. Baxi ◽  
C. J. Barclay ◽  
C. L. Gibbs

The mechanical efficiency of rat cardiac muscle was determined using a contraction protocol involving cyclical, sinusoidal length changes and phasic stimulation at physiological frequencies (1–4 Hz). Experiments were performed in vitro (27°C) using rat left ventricular papillary muscles. Efficiency was determined from measurements of the net work performed and enthalpy produced by muscles during a series of 40 contractions. Net mechanical efficiency was defined as the percentage of the total, suprabasal enthalpy output that appeared as mechanical work. Maximum efficiency was ∼15% at contraction frequencies between 2 and 2.5 Hz. At lower and higher frequencies, efficiency was ∼10%. Enthalpy output per cycle was independent of cycle frequency at all but the highest frequency used. The basis of the high efficiency between 2 and 2.5 Hz was that work output was also greatest at these frequencies. At these frequencies, the duration of the applied length change was well matched to the kinetics of force generation, and active force generation occurred throughout the shortening period.


1994 ◽  
Vol 193 (1) ◽  
pp. 65-78 ◽  
Author(s):  
C J Barclay

The mechanical efficiency of mouse fast- and slow-twitch muscle was determined during contractions involving sinusoidal length changes. Measurements were made of muscle length, force production and initial heat output from bundles of muscle fibres in vitro at 31 degrees C. Power output was calculated as the product of the net work output per sinusoidal length cycle and the cycle frequency. The initial mechanical efficiency was defined as power output/(rate of initial heat production+power output). Both power output and rate of initial heat production were averaged over a full cycle of length change. The amplitude of length changes was +/- 5% of muscle length. Stimulus phase and duration were adjusted to maximise net work output at each cycle frequency used. The maximum initial mechanical efficiency of slow-twitch soleus muscle was 0.52 +/- 0.01 (mean +/- 1 S.E.M. N = 4) and occurred at a cycle frequency of 3 Hz. Efficiency was not significantly different from this at cycle frequencies of 1.5-4 Hz, but was significantly lower at cycle frequencies of 0.5 and 1 Hz. The maximum efficiency of fast-twitch extensor digitorum longus muscle was 0.34 +/- 0.03 (N = 4) and was relatively constant (0.32-0.34) over a broad range of frequencies (4-12 Hz). A comparison of these results with those from previous studies of the mechanical efficiency of mammalian muscles indicates that efficiency depends markedly on contraction protocol.


1997 ◽  
Vol 200 (22) ◽  
pp. 2907-2912 ◽  
Author(s):  
G N Askew ◽  
I S Young ◽  
J D Altringham

The function of many muscles requires that they perform work. Fatigue of mouse soleus muscle was studied in vitro by subjecting it to repeated work loop cycles. Fatigue resulted in a reduction in force, a slowing of relaxation and in changes in the force-velocity properties of the muscle (indicated by changes in work loop shape). These effects interacted to reduce the positive work and to increase the negative work performed by the muscle, producing a decline in net work. Power output was sustained for longer and more cumulative work was performed with decreasing cycle frequency. However, absolute power output was highest at 5 Hz (the cycle frequency for maximum power output) until power fell below 20% of peak power. As cycle frequency increased, slowing of relaxation had greater effects in reducing the positive work and increasing the negative work performed by the muscle, compared with lower cycle frequencies.


2006 ◽  
Vol 39 ◽  
pp. S306 ◽  
Author(s):  
L.P. Dasi ◽  
H. Simon ◽  
L. Ge ◽  
F. Sotiropoulos ◽  
A. Yoganathan

Author(s):  
JOSE RAUL MEDINA LOPEZ ◽  
LUIS DANIEL MAZON ROMAN ◽  
JUAN MANUEL CONTRERAS JIMENEZ ◽  
JUAN CARLOS RUIZ-SEGURA

Objective: The aim of this study was to carry out comparative dissolution studies with warfarin sodium reference tablets under the hydrodynamic environments generated by the USP basket and paddle apparatus and flow-through cell using different agitation rates and dissolution media. Methods: Dissolution profiles were obtained with the USP basket and paddle apparatus at 50, 75, and 100 rpm and 900 ml of water as dissolution medium. After this, dissolution profiles of warfarin sodium were obtained with the USP paddle apparatus and flow-through cell method using 0.1 N hydrochloric acid, acetate buffer pH 4.5, phosphate buffer pH 6.8, and water. Spectrophotometric determination at 308 nm was carried out during 30 min. Dissolution profiles were compared with model-independent and model-dependent approaches. Results: Significant differences were found with mean dissolution time and dissolution efficiency at 50 and 75 rpm (*P<0.05). Makoid-Banakar was the best-fit model used to describe the in vitro release performance of warfarin sodium with 50-100 rpm and the USP basket and paddle apparatuses. Significant differences in all calculated parameters were found (*P<0.05) excepting percent dissolved at 30 min with 0.1 N hydrochloric acid and phosphate buffer pH 6.8. Conclusion: More research is necessary to identify the in vitro release performance of poorly soluble drugs under available USP apparatuses considering factors as agitation rate and kind of dissolution media. The knowledge of the in vitro release performance of reference drug products is important for the design of better generic formulations


Sign in / Sign up

Export Citation Format

Share Document