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Biomedical subjects

Jonathan C Jarvis

Publications and source records attributed to Jonathan C Jarvis.

11 recordsLinked to original sources

Counterpulsation from the skeletal muscle ventricle and the intraaortic balloon pump in the normal and failing circulations.

BACKGROUND: The intra-aortic balloon pump (IABP) is the device that is in most common use to provide cardiovascular support. A skeletal muscle ventricle (SMV) was configured to produce counterpulsation in the thoracic aorta similar to that obtained with an IABP. The hemodynamic effects of an IABP and a SMV in the same animal and in both normal and failing circulations were assessed. METHODS AND RESULTS: SMVs were connected to and IABPs were placed in the thoracic aorta of 12 anesthetized pigs. Hemodynamic parameters during the IABP- or the SMV-assisted beat were compared with those during the preassist beat. Acute heart failure was induced in 6 of the pigs by snaring the left anterior descending coronary artery (LAD). The hemodynamic effects of the IABP and the SMV were then reassessed. In the assisted cycles, SMV activation increased the mean aortic diastolic pressure (MADP) by 26.5+/-3.5%, the mean diastolic LAD flow by 48.4+/-7.2%, and endocardial viability ratio (EVR) by 31.6+/-3.8% (P<0.0001). In the same animals, IABP assist increased MADP by 19.8+/-2.3%, mean diastolic LAD flow by 37.2+/-3.9%, and EVR by 21.4+/-3.0% (P<0.0001). Under acute heart failure conditions, both SMV and IABP assist significantly increased MADP, mean diastolic LAD flow, and EVR. CONCLUSIONS: In both the normal and failing circulations, the SMV was an effective counterpulsator, providing cardiac assist that was at least equal to that available from an IABP. The SMV may therefore provide the proven benefits of an IABP in ambulant patients.

Animals↗

Adaptive conditioning of skeletal muscle in a large animal model (Sus domesticus).

Recognition of the adaptive capacity of mammalian skeletal muscle has opened the way to a number of clinical applications. For most of these, the fast, fatigue-susceptible fibres need to be transformed stably to fast, fatigue-resistant fibres that express the 2A myosin heavy chain isoform. The thresholds for activity-induced change are size-dependent, so although the requisite patterns of electrical stimulation are known for the rabbit, in humans these same patterns would produce type 1 fibre characteristics, with an undesirable loss of contractile speed and power. We have used histochemistry, immunohistochemistry and electrophoretic separations to evaluate a possible conditioning regime in a large animal model. Stimulation of the porcine latissimus dorsi muscle with a phasic 30-Hz pattern for up to 41 days converted all type 2X and 2A/2X fibres to 2A with only a small increase in the type 1 population, from 17% to 22%. Stimulation for longer periods increased the proportion of type 1 fibres to 52%. Based on this model, stimulation regimes designed to achieve a stable 2A phenotype in humans should deliver fewer stimulating impulses, possibly by a factor of 2, than the pattern assessed here. Any such pattern needs to be tested for at least 8 weeks.

Adaptation, Physiological↗

Determination of the chronaxie and rheobase of denervated limb muscles in conscious rabbits.

Measurements of the rheobase and chronaxie can be used to define the excitability of nerves and muscles. The aim of this study was to obtain a record over many weeks of changes in the rheobase and chronaxie of denervated rabbit tibialis anterior muscle (TA). A custom-built electronic stimulator was implanted into the peritoneal cavity of New Zealand White rabbits. Large stainless steel electrodes were placed on the denervated TA muscle. Rheobase and chronaxie were measured noninvasively at weekly intervals by means of a laptop PC, which communicated with the stimulator via a radio-frequency link. At each setting the denervated TA was palpated manually to detect the response of the muscle. During the first few days after denervation the rheobase increased transiently to 0.8 +/- 0.13 mA, approximately twice the value for normal innervated muscle, then decreased to normal for the remainder of the experimental period. Chronaxie underwent a significant 3-fold increase from 4.5 +/- 1.1 ms to 14.1 +/- 1.1 ms during the first two weeks of denervation and remained elevated throughout. The custom-built implantable electronic stimulator allowed changes in muscle excitability to be studied over a long period of denervation within individual animals, providing an accurate assessment of the time course of denervation-induced changes in muscle excitability.

Analysis of Variance↗

A nonradioactive assay for nitric oxide synthase activity in tissue extracts.

We describe a fluorescence assay for nitric oxide synthase activity based on a new indicator, 4,5-diaminofluorescein (DAF-2). The method offers the advantage of being safer and more convenient than the citrulline radioassay in common use. The rapid and irreversible binding of DAF-2 to oxidized nitric oxide (NO) enables NO production to be measured in real time. The protocol is applied to the measurement of nitric oxide synthase in crude extracts of skeletal muscle.

Animals↗

Improved viability of latissimus dorsi muscle grafts after electrical prestimulation.

Surgical mobilization of the latissimus dorsi muscle (LDM) produces fiber degeneration, particularly in the distal part of the graft, that may compromise its function in clinical applications such as dynamic cardiomyoplasty. In five rats, the left LDM was stimulated continuously at 10 HZ. After 5 weeks, vessels perforating the chest wall were divided and the left LDM was mobilized as a pedicle graft based on the thoracodorsal artery. Twenty-four hours later, animals were killed and left and right LDMs were incubated with the vital stain nitroblue tetrazolium. Five control rats underwent a similar procedure without prestimulation. Mobilization of the LDM resulted in a loss of viability in the distal third of the muscle graft. This was reduced significantly by prestimulation (P = 0.006). Blood flow to the distal LDM graft is known to be augmented by electrical stimulation in situ before mobilization; the present results show that there is an associated enhancement of viability. The clinical implications of this finding are discussed.

Animals↗

Avoiding ischemia in latissimus dorsi muscle grafts: electrical prestimulation versus vascular delay.

BACKGROUND: Surgical mobilization of the latissimus dorsi muscle produces regional ischemic damage that may compromise its function in clinical applications such as cardiomyoplasty. We compared the effectiveness of two procedures designed to maintain blood flow throughout the mobilized muscle. METHODS: Adult pigs were assigned to two experimental groups: an electrically prestimulated group (n = 10) and a vascular delay group (n = 10). In the prestimulated group the left latissimus dorsi muscle was activated in situ at 2 Hz for 24 h/d. In the vascular delay group, the intercostal perforating arteries to the left latissimus dorsi muscle were divided. Two weeks later, hyperemic blood flow was measured by means of fluorescent microspheres immediately before and after mobilizing the latissimus dorsi muscle and again after recovery for a further 2 days. RESULTS: In the prestimulated group, blood flow was not significantly depressed in any region of the muscle immediately after mobilization, and blood flow increased significantly in proximal (p = 0.01), middle (p = 0.02), and distal (p = 0.007) regions following recovery. In muscles subjected to vascular delay the proximal and middle regions showed no significant changes in blood flow after mobilization or recovery, but flow in the distal region was 50% lower after mobilization (p = 0.003), and it remained significantly depressed even after recovery (p = 0.008). CONCLUSIONS: Prestimulation was significantly more effective than vascular delay in preserving distal blood flow. Because it is also less invasive and initiates metabolic transformation before mobilization, this technique should allow cardiac assistance to be introduced at an earlier postoperative stage without compromising the viability of the grafted muscle.

Animals↗

The hemodynamic function of intrathoracic skeletal muscle ventricles after recovery from surgery in pigs.

The shortage of donor organs for heart transplantation highlights the need for new approaches to end-stage heart failure. A promising experimental technique is the use of pumping chambers formed from the latissimus dorsi muscle. We formed such skeletal muscle ventricles (SMVs) and connected them to the descending thoracic aorta in a single surgical procedure in pigs. Activation of conditioned SMVs from the end of systole for 80% of diastole increased mean aortic diastolic blood pressure by 11.2 +/- 1.6% in 1 animal and by 15.8 +/- 0.3% in another. The left-ventricular stroke work in the postassisted beat was decreased by 8.7 +/- 5.8% and 10.1 +/- 2.2% and the overall stroke work by 7.4 +/- 1.2% and 9.4 +/- 0.8%. The key to forming and connecting the SMV in a single procedure was the use of a composite homograft lining. In future clinical practice, this component could be replaced by a synthetic composite or by a tissue lining produced in vitro.

Animals↗

The optimal stimulation pattern for skeletal muscle is dependent on muscle length.

Stimulation patterns can be optimized by maximizing the force-time integral (FTI) per stimulation pulse of the elicited muscle contraction. Such patterns, providing the desired force output with the minimum number of pulses, may reduce muscle fatigue, which has been shown to correlate to the number of pulses delivered. Applications of electrical stimulation to use muscle as a controllable biological actuator may, therefore, be improved. Although muscle operates over a range of lengths, optimized patterns have been determined only at optimal muscle length. In this study, the patterns with up to four pulses that produced the highest isometric FTI were determined at 10 muscle lengths for 11 rabbit tibialis anterior muscles. The interpulse intervals (IPIs) used ranged from 4 to 54 ms. At high muscle length, the optimal stimulation pattern consisted of an initial short IPI (doublet) followed by longer IPIs, in agreement with previous studies. However, at low length, the third pulse still elicited more than linear summation (triplet); furthermore, the relative enhancement of the FTI per pulse was considerably larger at low length than at high length, suggesting that optimal stimulation patterns are length dependent.

Animals↗

Skeletal muscle ventricles with a single-limb conduit: the importance of hemodynamic design.

BACKGROUND: Skeletal muscle ventricles (SMVs) connected to the descending thoracic aorta have the potential for providing long-term diastolic augmentation. A successful existing design employs a bifurcated conduit, but aortic constriction between the limbs of the conduit is required to ensure obligatory flow-through. Here we evaluate an alternative approach in which connection to the aorta is made by a single-limb conduit. METHODS: In two groups of dogs SMVs were constructed from the left latissimus dorsi muscle and connected to the circulation via a single-limb conduit of length 110-120 mm (Group 1, n = 5) or 70 mm (Group 2, n = 5). The animals were followed over 10 weeks. RESULTS: Although all animals showed significant augmentation of diastolic aortic pressure at the outset, substantial thrombus developed in the SMVs of both groups. The results were analyzed by reference to design criteria for a single-limb conduit SMV, developed from empirical, in-vitro flow studies and formulated mathematically. CONCLUSION: The SMVs constructed in this experiment appeared to meet the criteria for adequate mixing of blood within the ventricle. They did not, however, achieve adequate exchange of blood with the circulation. Thrombosis was therefore attributable to excessive residence time of blood in the SMV and conduit. Both the experimental study and the mathematical analysis point to the need for SMVs of this configuration to be constructed closer to the aorta. Preliminary results are reported for such an experiment in the pig, in which the SMV was thrombus-free when terminated electively after 1 week.

Animals↗