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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. [ABSTRACT FROM AUTHOR]

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 last 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. [ABSTRACT FROM AUTHOR]

Although denervating injuries produce severe atrophic changes in mammalian skeletal muscle, a degree of functional restoration can be achieved through an intensive regime of electrical stimulation. An implantable stimulator was developed so that the long-term effects of different stimulation protocols could be compared in rabbits. The device, which is powered by two lithium thionyl chloride batteries, is small enough to be implanted in the peritoneal cavity. All stimulation parameters can be specified over a wide range, with a high degree of resolution; in addition, up to 16 periods of training (10-180 min) and rest (1-42 h) can be set in advance. The microcontroller-based device is programmed through a bidirectional radiofrequency link. Settings are entered via a user-friendly computer interface and annotated to create an individual study protocol for each animal. The stimulator has been reliable and stable in use. Proven technology and rigorous quality control has enabled 55 units to be implanted to date, for periods of up to 36 weeks, with only two device failures (at 15 and 29 weeks). Changes in the excitability of denervated skeletal muscles could be followed within individual animals. Chronaxie increased from 3.24 +/- 0.54 ms to 15.57 +/- 0.85 ms (n = 55, p < 0.0001) per phase in the 2 weeks following denervation. [ABSTRACT FROM AUTHOR]