Cardiomyoplasty. A critical review of experimental and clinical results.
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Acute Disease↗
Biomedical subjects
J C Jarvis
Publications and source records attributed to J C Jarvis.
Fibre type composition of rabbit tibialis anterior and extensor digitorum longus muscles.
Rabbit tibialis anterior (TA) and extensor digitorum longus (EDL) muscles are used extensively in studies of stimulation-induced fibre type transformation, but the proportions and sizes of the 2 main fibre types, and the way in which they are distributed within the muscles, have never been described in any detail. In this study, transverse sections were processed by enzyme histochemical and immunohistochemical techniques and assessed morphometrically. The data were analysed by multivariate methods. In both TA and EDL muscles, the proportion of type 1 fibres varied significantly, and to a similar extent, within a cross-section, from lateral to medial and from superficial to deep parts. The fibre density, an indirect estimate of the mean muscle fibre area, also varied significantly, but not systematically, within a cross-section. For the EDL muscle, the proportion of type 1 fibres was consistently higher in the distal than in the proximal part of the muscle. The proportion of type 1 fibres was also significantly higher in the EDL than in the TA muscle for each of the 6 rabbits. There was no systematic variation between muscles from left and right limbs. The type proportions and fibre densities for both TA and EDL muscles differed significantly between individual rabbits, but not between sexes. The study provides a database that has hitherto been lacking on normal fibre type composition and its variation within and between these experimentally important muscles.
Adenosine Triphosphatases↗
Stimulation-induced expression of slow muscle myosin in a fast muscle of the rat. Evidence of an unrestricted adaptive capacity.
Fast muscles of the rat hind limb were stimulated continuously at 10 or 20 Hz for periods of 55-61 days by means of an implantable neuromuscular stimulator. Gel electrophoresis clearly demonstrated the presence in stimulated muscles of slow myosin light and heavy chains, although fast isoforms were still present in all cases. Thus, contrary to previous reports, induction of slow myosin isoforms does occur in this, as in other, mammalian species. The time course of the response to stimulation appears to be more extended than that seen in the rabbit.
Adaptation, Physiological↗
Power production and working capacity of rabbit tibialis anterior muscles after chronic electrical stimulation at 10 Hz.
1. The muscles of the distal anterior compartment of the left hindlimb of rabbits were subjected to continuous indirect electrical stimulation at 10 Hz for periods of up to 12 weeks by means of an implantable stimulator. 2. The maximum shortening velocity (Vmax) and the velocity for maximum power production in single contractions (Vopt) were reduced to 42% and 32% of control values respectively after 12 weeks of stimulation. The rate of change of these parameters was greatest between the second and sixth week of stimulation. These changes, it is suggested, reflect the documented time course of the replacement of fast with slow isoforms of myosin. 3. The reductions in force production and speed of the stimulated muscles combined to produce a marked, progressive decline in the maximum power produced in single contractions. After 8 weeks of stimulation, the maximum power output had fallen to less than 10% of the control value. 4. The fatigue resistance of the stimulated and control muscles was tested over several hours of cyclical shortening contractions designed to elicit an initial power output of 10 W kg-1 with the muscles set to contract at Vopt. This level of work output represented about 1.6% (control) and 25% (12-week-stimulated) of the absolute maximum power output achieved during single contractions. 5. Despite the large reduction in the maximum power output of single contractions, the stimulated muscles showed less than 10% reduction in their power output during the fatigue tests over periods of up to 7 h. The control muscles showed a 70% reduction over the same period. There was no difference in the fatigue resistance under this protocol between muscles stimulated for 2 weeks and those stimulated for longer periods. Transformation of myosin isoforms, which is known to occur later than 2 weeks after the start of stimulation, is not necessary for the induction of this degree of fatigue resistance.
Animals↗
Reciprocal changes in myosin isoform mRNAs of rabbit skeletal muscle in response to the initiation and cessation of chronic electrical stimulation.
Changes in myosin heavy chain (MHC) mRNAs were studied in rabbit fast-twitch muscles during continuous electrical stimulation at 10 Hz for periods up to 3 weeks, and during the first 12 days of the recovery process that followed cessation of 6 weeks' stimulation. Two cDNA probes were used to detect MHC mRNAs specific to fast- and slow-twitch skeletal muscle in RNase protection assays and Northern- and slot-blot analyses. The isolation and base sequence of one of these probes, corresponding to the MHC gene expressed in soleus (slow-twitch), is described. At an early stage of the response to stimulation, fast MHC mRNA was replaced by slow MHC mRNA. During recovery, this process occurred in reverse but took longer. The time course of recovery was slightly faster in tibialis anterior than in extensor digitorum longus. The changes in mRNAs during both stimulation and recovery reflected changes in the corresponding muscle proteins.
Animals↗
Cardiac assistance from skeletal muscle: a critical appraisal of the various approaches.
We review here various ways in which cardiac assistance might be derived from a patient's own skeletal muscle. Calculations based on experimental data and optimistic estimates of the efficiency of the energy conversions involved suggest that the continuous assist available would be limited to about 2 litres a minute if a muscle were used to energise an electromechanical device. It would be more efficient to couple the energy mechanically or hydraulically, but these approaches still pose problems of anatomical placement, muscle attachment, fluid leakage, and cost. Unless these issues can be addressed, the use of skeletal muscle as an internal power source for mechanical circulatory assist devices will remain an unworkable concept. Configurations that couple skeletal muscle contraction directly to the circulation would be more efficient and less costly. In terms of the energy available, a skeletal muscle ventricle could be designed to provide a continuous partial assist of 1-2 l/min, with flows of up to 8 l/min sustainable for limited periods. Such an approach offers new possibilities for the surgical treatment of chronic cardiac failure.
Blood Circulation↗
Reciprocal changes in myosin isoform expression in rabbit fast skeletal muscle resulting from the application and removal of chronic electrical stimulation.
Chronic indirect electrical stimulation of adult mammalian skeletal muscle brings about a transformation from the fast-twitch to the slow-twitch type. Underlying this transformation there is a sequence of profound changes in the expression of proteins involved in all the major molecular systems of the muscle. These include qualitative changes in the expression of myosin light and heavy chain isoforms. The time course of these changes has been studied in some detail at the protein level, both during chronic stimulation and during the recovery process that follows the cessation of stimulation. Here we report on the use of cDNA probes to study corresponding changes in myosin heavy chain (MHC) and light chain (MLC) mRNAs in rabbit fast-twitch muscles during continuous electrical stimulation at 10 Hz and during the first 12 days of recovery after cessation of 6 weeks of stimulation. At an early stage of the response to stimulation, fast MHC mRNA is replaced by slow MHC mRNA. During recovery this process occurs in reverse but takes longer. Broadly similar changes are seen for MLC mRNAs, although the time course is somewhat different. These experiments contribute to a growing body of evidence that many of the protein changes induced by chronic stimulation are the result of regulatory events that take place at a pre-translational level.
Animals↗
Programmable implantable device for investigating the adaptive response of skeletal muscle to chronic electrical stimulation.
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Adaptation, Physiological↗
Simple optical switch for implantable devices.
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Electronics, Medical↗
Basic studies on skeletal muscle for cardiac assistance.
It is well recognized that skeletal muscle is incapable of maintaining the continuous power output needed for significant circulatory assistance unless it is rendered fatigue resistant by electrical stimulation. Most studies using conditioning patterns related to the pumping rate of the natural heart have suggested that such patterns can produce complete transformation to a slow phenotype. Such a transformation has two undesirable accompaniments: a reduction in the contractile speed of the muscle and an extreme reduction in its power-generating capacity. We have investigated the chronic effect on rabbit muscle of intermittent high frequency contractions either alone or overlaid on a continuous background of 10 Hz. If the amount of stimulation were the overriding stimulus for transformation, then the rate and/or extent of transformation should, if anything, be greater with the additional activation. If, on the other hand, components of the transformation could be modulated independently by the pattern of impulses, then the reduction in power output might be avoided to some extent by a pattern somewhat analogous to a strength-training exercise regime. Our results suggest that high force contractions may indeed preserve power output without compromising the acquisition of fatigue resistance.
Adaptation, Physiological↗
An electrohydraulic apparatus for the measurement of static and dynamic properties of rabbit muscles.
The apparatus described in this communication enables the force-velocity relationship to be determined for whole rabbit muscles in vivo and their resistance to fatigue to be assessed at specified rates of external work. The ergometer generates constant-velocity motion, controlling a force of up to 50 N, over a range of velocity up to 500 mm/s and a distance of 20 mm. This distance corresponds to the range of shortening of the rabbit tibialis anterior muscle from full plantar flexion to full dorsiflexion of the foot, equivalent to approximately 28% fiber shortening. Activated muscles can be allowed to shorten at constant velocity from any point on their isometric force trajectory. Cyclic releases for fatigue testing can be made at rates up to 30 releases/min over a period of 6-8 h. The timing of the release and return strokes of the ergometer is under the control of a digital programmer that also synchronizes the delivery of activating stimuli to the muscle nerve and trigger signals to the recording equipment. An electrohydraulic design was chosen because it is simpler to engineer than an electromagnetic actuator, is reliable in continuous cyclic use, and can be assembled, at least in part, from available industrial components.
Animals↗
Low frequency chronic electrical stimulation of normal and dystrophic chicken muscle.
The fast-twitch posterior latissimus dorsi muscle of normal and genetically dystrophic chickens was subjected to continuous indirect electrical stimulation at 10 Hz for periods of 4-8 weeks. To sustain this in vivo nerve stimulation an internally implantable miniature stimulator device was designed. This regime of stimulation caused complete fatigue of the normal muscle within 5 min of its initiation. The dystrophic muscles maintained a very small degree of contractile activity during this initial phase. Tangible twitching of the muscle returned in 5 week birds between 3 and 5 days and in 10 week birds between 11 and 16 days after implantation. After 4 weeks of stimulation, no significant change was measured in the time-to-peak of the isometric twitch response, nor in the half-relaxation time. The resistance to fatigue was significantly increased in the stimulated muscles when tested with a series of tetani at 40 Hz. The mean fibre area was decreased, in all muscles stimulated for longer than 3 weeks, in comparison to their contralateral controls, except where fibre splitting in dystrophic birds abnormally reduced the control value. The majority fibre type of the muscle was changed from type IIB to IIA. The histochemical reactions for both NADH-linked oxidation and phosphorylase were distinctly increased in the stimulated muscles. In normal muscle, stimulation increased somewhat the number of nuclei per unit area and changed their intracellular distribution, so that a greater proportion was found adjacent to the sarcolemma. The normal posterior latissimus dorsi muscle responded to chronic stimulation with increases of 3-6-fold in its acetylcholinesterase (AChE) activity. The maximum change in AChE occurred after 2 weeks stimulation; a steady level, 3 times that of the control unstimulated muscle, persisted at later times. Chronic stimulation suppressed the over-production of AChE that is characteristic of dystrophic chicken fast-twitch muscle, to attain a level comparable to the AChE activity in a stimulated normal muscle. Stimulation exerted a strong normalizing influence on dystrophic muscle, as assessed morphologically. The characteristic fibre rounding, fibre hypertrophy and myonuclear proliferation were reduced. This influence was most marked where the stimulation was initiated before the major pathological changes had occurred, but was also significant when commenced in strongly affected birds of 10-11 weeks.
Acetylcholinesterase↗
Effects of cardiomyoplasty on cardiac growth in rats.
BACKGROUND AND AIM OF THE STUDY: Cardiomyoplasty (CMP) has been proposed as a treatment for pediatric patients, but restriction of cardiac growth by the muscle wrap is a potential source of concern. This possibility was investigated in an immature animal model. METHODS: Six-week-old rats (body weight 203.8 +/- 5.4 g, mean +/- SEM) underwent either left thoracotomy with CMP (group I, n = 7), or thoracotomy without CMP (group II, n = 8). A third group (group III, n = 7) served as untreated controls. Final measurements were made 20 weeks later after body weights had reached a plateau. RESULTS: Preoperative body weights were not significantly different between the groups. At elective sacrifice, the body weights of animals that underwent surgery did not differ significantly (group I, 558.0 +/- 21.5 g and group II, 617.3 +/- 20.3 g), but were significantly less than those of control animals (727.6 +/- 13.3 g, p < 0.001 and p < 0.01, respectively). Cardiac ventricular weights in the CMP group were significantly less than those of control animals (group I, 1.21 +/- 0.06 g; group III 1.45 +/- 0.04 g; p < 0.01), but were not statistically different from those of the sham thoracotomy group (group II, 1.36 +/- 0.05 g). Mean left ventricular end-diastolic volumes were similar in all groups (group I, 0.67 +/- 0.07 mL; group II, 0.66 +/- 0.07 mL; and group III, 0.69 +/- 0.10 mL; p = ns). CONCLUSIONS: A major surgical procedure impairs growth in juvenile rats. no evidence emerged from this study for additional restriction of cardiac development due to cardiac wrapping. However, studies that include stimulated muscle wraps are needed before CMP should be considered for the pediatric age group.
Animals↗
A family of neuromuscular stimulators with optical transcutaneous control.
A family of miniature implantable neuromuscular stimulators has been developed using surface-mounted Philips 4000-series integrated circuits. The electronic components are mounted by hand on printed circuits (platinum/gold on alumina) and the electrical connections are made by reflow soldering. The plastic integrated-circuit packages, ceramic resistors and metal interconnections are protected from the body fluids by a coating of biocompatible silicone rubber. This simple technology provides reliable function for at least 4 months under implanted conditions. The circuits have in common a single lithium cell power-supply (3.2 V) and an optical sensor which can be used to detect light flashes through the skin after the device has been implanted. This information channel may be used to switch the output of a device on or off, or to cycle through a series of pre-set programs. The devices are currently finding application in studies which provide an experimental basis for the clinical exploitation of electrically stimulated skeletal muscle in cardiac assistance, sphincter reconstruction or functional electrical stimulation of paralysed limbs.
Adaptation, Physiological↗
Factors affecting the integrity of latissimus dorsi muscle grafts: implications for cardiac assistance from skeletal muscle.
BACKGROUND: Severe latissimus dorsi muscle damage may compromise cardiomyoplasty performance. We analyzed factors underlying the damage produced in 20 sheep latissimus dorsi muscles by isolating the influences of electrical stimulation, mobilization (with some loss of vascular supply), loss of normal resting tension, or a combination of these. METHODS: In group I (n = 3), the muscle was mobilized except for its neurovascular pedicle and reattached at normal resting length. In group II (n = 3), the muscle was mobilized and reattached at about 80% of resting length. Groups III (n = 6) and IV (n = 4) were as groups I and II except that continuous indirect stimulation at 2 Hz was added after 2 weeks. In group V (n = 4), the undisturbed muscle received stimulation alone. After 10 to 12 weeks, muscle samples were taken for morphometric analysis. RESULTS: Loss of resting muscle tension appeared to be the single most damaging intervention, though mobilization and stimulation had further deleterious effects. The worst damage was seen when all three factors were combined, when 60% of the muscle cross section was occupied by connective tissue and fat. The changes were significantly more severe in the distal than in the proximal part of the muscle, implicating ischemia as a contributory factor. CONCLUSIONS: Fiber damage reduces the effectiveness of muscle grafts used for cardiac assistance and merits further systematic investigation.
Adipose Tissue↗