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Biomedical subjects

J C Jarvis

Publications and source records attributed to J C Jarvis.

At least 19 recordsLinked to original sources

Atrophy, but not necrosis, in rabbit skeletal muscle denervated for periods up to one year.

Our understanding of the effects of long-term denervation on skeletal muscle is heavily influenced by an extensive literature based on the rat. We have studied physiological and morphological changes in an alternative model, the rabbit. In adult rabbits, tibialis anterior muscles were denervated unilaterally by selective section of motor branches of the common peroneal nerve and examined after 10, 36, or 51 wk. Denervation reduced muscle mass and cross-sectional area by 50-60% and tetanic force by 75%, with no apparent reduction in specific force (force per cross-sectional area of muscle fibers). The loss of mass was associated with atrophy of fast fibers and an increase in fibrous and adipose connective tissue; the diameter of slow fibers was preserved. Within fibers, electron microscopy revealed signs of ultrastructural disorganization of sarcomeres and tubular systems. This, rather than the observed transformation of fiber type from IIx to IIa, was probably responsible for the slow contractile speed of the muscles. The muscle groups denervated for 10, 36, or 51 wk showed no significant differences. At no stage was there any evidence of necrosis or regeneration, and the total number of fibers remained constant. These changes are in marked contrast to the necrotic degeneration and progressive decline in mass and force that have previously been found in long-term denervated rat muscles. The rabbit may be a better choice for a model of the effects of denervation in humans, at least up to 1 yr after lesion.

Animals↗

Two-way communication for programming and measurement in a miniature implantable stimulator.

Implantable stimulators are needed for chronic electrical stimulation of nerves and muscles in experimental studies. The device described exploits the versatility of current microcontrollers for stimulation and communication in a miniature implant. Their standard outputs can provide the required selectable constant-current sources. In this device, pre-programmed stimulation paradigms were selected by transcutaneous light pulses. The potential of a programmable integrated circuit (PIC) was thus exploited. Implantable devices must be biocompatible. A novel encapsulation method that require no specialised equipment and that used two classical encapsulants, silicone and Teflon was developed. It was tested for implantation periods of up to four weeks. A novel way to estimate electrode impedance in awake animals is also presented. It was thus possible to follow the evolution of the nerve-electrode interface and, if necessary, to adjust the stimulation parameters. In practice, the electrode voltage at the end of a known constant-current pulse was measured by the PIC. The binary coded value was then indicated to the user as a series of muscle twitches that represented the binary value of the impedance measurement. This neurostimulator has been successfully tested in vitro and in vivo. Thresholds and impedance values were chronically monitored following implantation of a self-sizing spiral cuff electrode. Impedance variations in the first weeks could reflect morphological changes usually observed after the implantation of such electrodes.

Animals↗

Use what you have--biological assistance for the treatment of heart failure in the Caribbean.

Cardiovascular disease represents the main cause of death among adults in the Caribbean. Primary and secondary care facilities are efficiently managed. Cardiac surgical and interventional facilities, however, exist only in a small number of territories and are mainly privately funded and are only accessible to few patients. Patients with end-stage heart failure (ESHF) are given few options apart from palliative care or to seek treatment outside of the region. Transplantation remains the 'gold standard' therapy for ESHF. Establishing a Caribbean cardiac transplantation programme would require legislative and infrastructure changes. Tissue rejection poses a problem and expensive immunosuppressants are needed. Mechanical assist devices are costly and associated with complications such as haemorrhage, thrombosis and infections. Both forms of therapy require significant technical and financial investment and do not appear to be economically viable for the Caribbean. The use of the patient's own skeletal muscle to perform biological cardiac assistance is potentially the ideal alternative. The skeletal muscle is conditioned by electrical stimulation to become fatigue resistant. It is then transposed and harnessed as an auxilliary circulatory pump. The required muscle stimulators are relatively inexpensive and the surgical techniques and postoperative care are not overly demanding. We discuss the financial and research implications of treating patients from the Caribbean who have end-stage heart failure.

Cardiomyoplasty↗

Experimental determination of compound action potential direction and propagation velocity from multi-electrode nerve cuffs.

Information extracted from whole-nerve electroneurograms, recorded using electrode cuffs, can provide signals to neuroprostheses. However, the amount of information that can be extracted from a single tripole is limited. This communication demonstrates how previously unavailable information about the direction of action potential propagation and velocity can be obtained using a multi-electrode cuff and that the arrangement acts as a velocity-selective filter. Results from in vitro experiments on frog nerves are presented.

Action Potentials↗

Haemodynamic considerations in the design of a skeletal muscle ventricle.

Skeletal muscle ventricles (SMVs) configured to operate as diastolic counterpulsators show promise as cardiac assist devices. In four pigs, SMVs were connected to the aorta by a single-limbed conduit and activated during every third cardiac diastole. During the assisted beats, mean diastolic aortic pressure increased by 30.3 +/- 2.2%, peak diastolic aortic pressure increased by 38.5 +/- 2.7%, the endocardial viability ratio increased by 42.3 +/- 3.4%, and mean left anterior descending coronary artery flow increased by 61.6 +/- 4.5%. Although there are major advantages to making the connection to the aorta by a single-limb conduit, the lack of separation between inlet and outlet means that such devices must be designed carefully to avoid thrombogenesis under chronic conditions. Design rules were developed for this configuration, based on earlier in vitro studies. They addressed the problem of stasis by promoting the development of a propagating vortex that travels the length of the ventricle and ensured proper exchange of blood with the circulation by limiting the volume of the connecting conduit. An SMV compatible with these rules was connected in a pig. At elective termination 1 week later, activation of the SMV increased peak diastolic pressure by 20.1% and reduced left-ventricular stroke work in the post-assisted beat by 10.1%. The SMV was free from thrombus.

Animals↗

A fluorescence-based method for measuring nitric oxide in extracts of skeletal muscle.

We describe here a fluorescence assay for nitric oxide synthase activity in skeletal muscle based on a new indicator, 4,5-diaminofluorescein (DAF-2). The rapid and irreversible binding of DAF-2 to oxidized NO allows real-time measurement of NO production. The method is safer and more convenient than the usual citrulline radioassay and can be used with crude muscle extracts. Rabbit fast tibialis anterior (TA) muscle had a nitric oxide synthase (NOS) activity of 44.3 +/- 3.5 pmol/min/mg muscle. Addition of NOS blocker N(G)-allyl-L-arginine reduced this activity by 43%. Slow soleus muscle displayed NOS activity of 7.3 +/- 2.5 pmol/min/mg muscle, 16% that of the TA muscle. Continuous stimulation of TA muscle at 10 Hz for 3 weeks reduced NOS activity by 47% to an intermediate value consistent with the associated conversion of the muscle phenotype from fast to slow.

Animals↗

Combination of preconditioning and delayed flap elevation: evidence for improved perfusion and oxygenation of the latissimus dorsi muscle for cardiomyoplasty.

BACKGROUND: Atrophy and fibrosis of the distal part of the latissimus dorsi muscle (LDM) wrap is a recognized complication of cardiomyoplasty that has been attributed to ischemia. Failure of the muscle wrap contributes to the late attrition seen in clinical cardiomyoplasty. In this study we examined the role of two-staged mobilization and of preconditioning by electrical stimulation on the regional perfusion and oxygenation of the LDM. METHODS: In a rabbit model (n = 36) the LDM was preconditioned as follows: group A muscles received preconditioning in situ; group B muscles were partially mobilized by dividing the intercostal perforators and then preconditioned; and group C muscles were completely mobilized and wrapped around a silicone-rubber mandrel before conditioning. Controls received no conditioning. The preconditioning regimen consisted of 2 weeks of continuous stimulation at 2.5 Hz. At completion of preconditioning the muscles were fully mobilized and mounted on a muscle-testing apparatus. Purpose-built microelectrodes measured regional PO2 and perfusion using a diffusible gas tracer technique. Muscles were weighed and processed for fiber typing and capillary counting. RESULTS: All preconditioned muscles demonstrated fiber transformation, with increased fatigue resistance. Perfusion of preconditioned muscles both at rest and during contraction was higher than control in the proximal part of the muscle. Distal regions of group B muscles had higher perfusion and capillary density than any other group (p < 0.05). Distal regions of group C had the lowest perfusion and capillary density, and showed muscle atrophy and histologic evidence of necrosis. During fatigue testing there was a decrease in the PO2 in the distal regions of the control and group C muscles (p < 0.05), whereas it was maintained at resting levels in both group A and B muscles. CONCLUSIONS: Conditioning in situ improves perfusion of the distal LDM and prevents a fall in tissue PO2 during contraction. Two-stage mobilization further improves distal perfusion and capillary density. In contrast, shortterm elevation followed by conditioning produces impaired distal perfusion, decrease in PO2, and fiber necrosis in the distal muscle. The present study suggests that partial mobilization of the LDM performed at the same time as placement of electrodes for preconditioning may prepare the LDM better for the demands of cardiomyoplasty.

Animals↗

Effects of a new cardiomyoplasty technique on cardiac function.

OBJECTIVE: The current cardiomyoplasty technique was modified to maintain the resting tension of the latissimus dorsi muscle and to prevent lateral movement of the heart during muscle stimulation. The aim of this study is to compare the short term hemodynamic effects of the new cardiomyoplasty wrap (W1) with those of the clinically applied cardiomyoplasty wrap (W2). Preliminary indications of the long-term hemodynamic effects of W1 are presented. METHODS: In three acute experiments in sheep mean central venous pressure (MCVP), mean arterial pressure (MAP), mean cardiac output (MCOP), mean left ventricular systolic pressure (MLVSP), and mean left ventricular diastolic pressure (MLVDP) were measured for 30s before and five minutes after applying each procedure with and without stimulation of the muscle graft. The same parameters were also recorded 5min after removing each muscle wrap. Hemodynamic changes associated with unstimulated muscle wraps were compared to the baseline data. Hemodynamic effects of muscle stimulation were determined by comparing the assisted to the preceding unassisted cardiac cycle. The long-term effects of W1 on the hemodynamics of another three sheep were studied at 6-12months after the operation. The viability of the muscles used in the chronic experiments were evaluated by morphometric analysis. RESULTS: Unstimulated W2 significantly increased mean central venous pressure and reduced mean cardiac output. It also increased mean left ventricular diastolic pressure and reduced peak negative dP/dt. Unstimulated W1 had no deleterious effect on mean central venous pressure, mean left ventricular diastolic pressure or peak -dP/dt, but it also reduced mean cardiac output and increased mean left atrial pressure (MLAP). Synchronised muscle stimulation, in both techniques, augmented the mean arterial pressure, mean cardiac output and mean left ventricular systolic pressure. In W2, however, myostimulation was also associated with a significant increase of the mean left ventricular diastolic pressure. In two long-term experiments significant hemodynamic assistance was observed at 6months and at 1yr after W1. In those sheep 68% of the cross-sectional area of the muscle was well preserved. CONCLUSIONS: Unstimulated cardiomyoplasty wraps acutely impair left ventricular function in sheep. The new technique, however, may offer significant long-term hemodynamic assistance and adequate preservation of the structural and functional integrity of the muscle flap for up to 1yr.

Animals↗

ASIC or PIC? Implantable stimulators based on semi-custom CMOS technology or low-power microcontroller architecture.

To gain a better understanding of the effects of chronic stimulation on mammalian muscles we needed to generate patterns of greater variety and complexity than simple constant-frequency or burst patterns. We describe here two approaches to the design of implantable neuromuscular stimulators that can satisfy these requirements. Devices of both types were developed and used in long-term experiments. The first device was based on a semi-custom Application Specific Integrated Circuit (ASIC). This approach has the advantage that the circuit can be completely tested at every stage of development and production, assuring a high degree of reliability. It has the drawback of inflexibility: the patterns are produced by state machines implemented in silicon, so each new set of patterns requires a fresh production run, which is costly and time-consuming. The second device was based on a commercial microcontroller (Microchip PIC16C84). The functionality of this type of circuit is specified in software rather than in silicon hardware, allowing a single device to be programmed for different functions. With the use of features designed to improve fault-tolerance we found this approach to be as reliable as that based on ASICs. The encapsulated devices can easily be accommodated subcutaneously on the flank of a rabbit and a recent version is small enough to implant into the peritoneal cavity of rats. The current devices are programmed with a predetermined set of 12 patterns before assembly; the desired pattern is selected after implantation with an electronic flash gun. The operating current drain is less than 40 microA.

Animals↗

A nonlinear approach to modeling of electrically stimulated skeletal muscle.

This paper is concerned with the development and analysis of a nonlinear approach to modeling of the contraction of electrically stimulated skeletal muscle. The model structure is based on a network of locally valid linear models which are blended together by a scheduler. Data are from experiments with rabbit tibialis anterior muscles in which the muscles contracted isometrically while being stimulated by supramaximal impulses with randomly varying inter-pulse intervals. The model accounts for nonlinear effects due to variations of the stimulation frequency, such as the "catch-like" effect. It is shown that this modeling technique is suitable for modeling the contraction of muscles with very different characteristics, such as muscle with a majority of fast motor units and muscle with mainly slow motor units. The approach is also suitable as a basis for the design of muscle stimulation controllers. Index Terms-Functional electrical stimulation, local model network, muscle modeling, nonlinear system identification.

Animals↗

Induction of a fatigue-resistant phenotype in rabbit fast muscle by small daily amounts of stimulation.

We have shown that fatigue resistance can be induced in rabbit tibialis anterior (TA) muscles without excessive power loss by continuous stimulation at low frequencies, such as 5 Hz, and that the same result is obtained by delivering a 10-Hz pattern in equal on/off periods. Here we ask whether the same phenotype could be produced with daily amounts of stimulation that would be more appropriate for clinical use. We stimulated rabbit TA muscles for 6 wk, alternating fixed 30-min on periods of stimulation at 10 Hz with off periods of different duration. All patterns transformed fast-glycolytic fibers into fast-oxidative fibers. The muscles had fatigue-resistant properties but retained a higher contractile speed and power production than muscles transformed completely to the slow-oxidative type. We conclude that in the rabbit as little as one 30-min period of stimulation in 24 h can result in a substantial increase in the resistance of the muscle to fatigue.

Animals↗

Functional assessment of skeletal muscle ventricles after pumping for up to four years in circulation.

BACKGROUND: The successful treatment of cardiac failure by heart transplantation is severely limited by the shortage of donor organs, and alternative surgical approaches are needed. An experimental approach that holds considerable promise is the skeletal muscle ventricle (SMV), an auxiliary blood pump formed from a pedicled graft of latissimus dorsi muscle and connected to the circulation in a cardiac assist configuration. Adaptive transformation, or conditioning, by electrical stimulation enables the skeletal muscle to perform a significant proportion of cardiac work indefinitely without fatigue. METHODS: In 10 dogs, SMVs were constructed from the latissimus dorsi muscle, lined internally with pericardium, and conditioned by electrical stimulation to induce fatigue resistant properties. The SMVs were connected to the descending thoracic aorta via two 12-mm Gore-Tex conduits and the aorta was ligated between the two grafts. The SMV was stimulated to contract during the diastolic phase of alternate cardiac cycles. The animals were monitored at regular intervals. RESULTS: At initial hemodynamic assessment, SMV contraction augmented mean diastolic blood pressure by 24.6% (from 61 +/- 7 to 76 +/- 9 mm Hg). Presystolic pressure was reduced by 15% (from 60 +/- 8 to 51 +/- 7 mm Hg) after an assisted beat. Four animals died early, 1 from a presumed arrhythmia, and 3 during propranolol-induced hypotension. The other 6 animals survived for 273, 596, 672, 779, 969, 1,081, and 1,510 days. Diastolic augmentation was 27.4% at 1 year (93 +/- 9 vs 73 +/- 6 mm Hg; n = 5), 34.7% at 2 years (85 +/- 6 vs 63 +/- 7 mm Hg; n = 3), 21.2% (89 +/- 10 vs 73 +/- 8 mm Hg; n = 2) at 3 years, and 34.5% (78 vs 58 mm Hg; n = 1) after 4 years in circulation. After 4 years, the isolated SMV was able to maintain a pressure of over 80 mm Hg while ejecting fluid at 20 mL/s. No animal showed evidence of SMV rupture or thromboembolism. CONCLUSIONS: The SMVs in this study provided effective and stable hemodynamic assistance over an extended period of time. There was no evidence that the working pattern imposed on the muscular wall of the SMV compromised its viability. Areas of fibrofatty degeneration were suggestive of early damage that future protocols should seek to minimize.

Animals↗

Oxygenation and perfusion of rabbit tibialis anterior muscle subjected to different patterns of electrical stimulation.

Dual amperometric microelectrodes were used to measure local pO2 and perfusion at multiple sites in the fast-twitch tibialis anterior muscles of anaesthetized rabbits. Six muscles were stimulated continuously at 10, 5, or 2.5 Hz. For all three frequencies, perfusion declined to about 50% of resting levels and recovered after stimulation. These changes corresponded to a rise followed by a fall in extracellular pO2. The highest levels of pO2 were reached during stimulation at 10 Hz. Eight muscles were stimulated tetanically at 100 Hz for 200 ms with duty cycles that were varied between 1.3 and 20.0%. Perfusion rose to 8.7 +/- 2.0 ml s(-1) 100 g(-1) at a duty cycle of 5% and declined with further increases in duty cycle. pO2 was depressed for duty cycles less than 10% but rose above resting levels at higher duty cycles. It is suggested that the paradoxical combination of elevated pO2 and depressed perfusion is attributable to stimulation conditions that exceed the oxygen transport capacity of a fast muscle.

Animals↗

Dynamics of stimulation-induced muscle adaptation: insights from varying the duty cycle.

We sought to gain insight into the dynamics of the signalling process that initiates adaptive change in mammalian skeletal muscles in response to chronic neuromuscular stimulation. Programmable miniature stimulators were implanted into rabbits and used to impose one of the following patterns on the dorsiflexors of one ankle: 10 Hz delivered in equal on/off periods of 30 s, 30 min, or 12 h (all equivalent in terms of aggregate impulse activity to continuous 5 Hz). Two further groups received continuous stimulation at 5 Hz or 10 Hz. In every case the stimulation pattern was maintained continuously for 6 weeks. Tibialis anterior muscles stimulated intermittently with equal on/off periods of 30 s, 30 min and 12 h had contractile characteristics that were significantly slower than the contralateral, unstimulated muscles but did not differ from those of muscles stimulated continuously at 5 Hz. Muscles stimulated continuously at 10 Hz were significantly slower than either contralateral muscles or muscles stimulated with any of the other patterns. Corresponding changes were seen in myosin heavy chain isoform composition. The fatigue index, defined as the fraction of tension remaining after 5 min of a standard fatigue test, was 0.4 for muscles in the contralateral group but equal to or greater than 0.85 for muscles of all the stimulated groups. These results were interpreted with the help of a simple model of the growth and decay of a putative signalling substance based on first order kinetics. The model suggests a rate constant for the accumulation of the signalling substance that is greater than 30 h(-1), and a rate constant for its removal that is greater than 50 h(-1).

Adaptation, Physiological↗

Cardiomyoplasty: the benefits of electrical prestimulation of the latissimus dorsi muscle in situ.

BACKGROUND: Ischemic damage in the latissimus dorsi muscle may limit the success of cardiomyoplasty. Electrical prestimulation of the muscle in situ is known to enhance thoracodorsal perfusion to the distal latissimus dorsi muscle immediately after grafting. In this study we asked whether prestimulation was also beneficial under typical postoperative conditions. METHODS: Ten sheep were randomly assigned to two equal groups. In one group the latissimus dorsi muscle was stimulated continuously in situ at 2 Hz for 2 weeks; in the other group the muscle was not stimulated. Regional blood flows in the muscle were determined sequentially (1) under baseline conditions, (2) immediately after surgical mobilization, handling, and reattachment at 80% of the resting length, and (3) after 5 days. RESULTS: Manipulation of the unstimulated muscle resulted in an acute global reduction in blood flow with no improvement after 5 days. The distal region was most severely affected (26.2%+/-4.2% of baseline blood flow). Electrical prestimulation significantly reduced regional blood flow under baseline conditions but rendered the whole muscle more resistant to the surgical manipulations; blood flow was significantly better-preserved immediately afterwards, and there was complete recovery to baseline levels after 5 days. CONCLUSIONS: Electrical prestimulation of the latissimus dorsi muscle in situ reduces the acute distal ischemia caused by surgical manipulations, and promotes subsequent recovery of blood flow to baseline levels after a few days. Use of a prestimulated graft may therefore improve the outcome of skeletal muscle cardiac assistance.

Animals↗

The dose-related response of rabbit fast muscle to long-term low-frequency stimulation.

Rabbit tibialis anterior muscles were stimulated continuously at 2.5 Hz, 5 Hz, or 10 Hz for 10 months. The resulting adaptive transformation was dose-related for contractile speed, myosin isoform composition, and enzyme activities. The "fast-oxidative" state produced by stimulation at 2.5 Hz was stable: even after 10 months, 84% of the fibers were of type 2A. Absence of a secondary decline in oxidative activity in these muscles provided strong evidence of a causal link between myosin transitions and metabolic adaptation. Significant fiber loss occurred only after prolonged stimulation at 10 Hz. The myosin isoform composition of individual muscles stimulated at 5 Hz resembled that of muscles stimulated at either the lower or the higher frequency, behavior consistent with a threshold for fiber type change. In clinical applications such as cardiomyoplasty, muscles could be used more effectively by engineering their properties to combine speed and power of contraction with the necessary resistance to fatigue.

Anaerobiosis↗

Intramuscular pressure, force and blood flow in rabbit tibialis anterior muscles during single and repetitive contractions.

The elevated intramuscular pressure (IMP) associated with sustained muscle contraction can affect blood flow, and could influence the long-term viability of functional skeletal muscle grafts. We therefore examined the relationship between force, peak IMP and blood flow in the tibialis anterior muscle of the anaesthetized rabbit. During isometric contractions. IMP was related linearly to force, and only the slope of the relationship varied between animals. During isotonic contractions, however, the highest values of IMP were found at the lowest force levels, and IMP appeared to be related to the amount and speed of shortening. During repeated isometric contractions, the ratio of IMP to force varied with time, stimulation pattern and subject. Mean blood flow did not differ appreciably between repetitive isometric contractions at duty cycles of 10-40%, and was unrelated to integrated pressure, integrated force, or depth from the surface. We conclude: (1) that IMP is unlikely to affect mean blood flow during cyclic activity that has a duty cycle less than 40%; and (2) that the clinical use of IMP as a predictor of muscle force appears to be justified only for single isometric contractions, and needs to be interpreted cautiously when contractions involve shortening or fatigue.

Animals↗