Physiologic characteristics of canine skeletal muscle: implications for timing skeletal muscle cardiac assist devices.

BACKGROUND: Optimal clinical stimulation for skeletal muscle cardiac assist systems (such as dynamic cardiomyoplasty) is not clearly defined. The pressure-generating capacity of canine skeletal muscle ventricles (SMVs) at a variety of preloads and stimulation frequencies was examined as was time for SMVs to develop peak pressure. METHODS: SMVs were analyzed just after construction and after 3 months of electrical conditioning. Pressure generation and time to develop peak pressure were determined using a distensible mandrel. RESULTS: Higher preloads resulted in increased pressure generation; conditioned SMVs generated significantly less pressure than unconditioned SMVs. Increasing stimulation frequency from 20 to 50 Hz increased pressure-generating capacity; increases beyond 50 Hz did not result in further increases. Time to 90% peak pressure was least at 10 HZ and 65 Hz. CONCLUSIONS: Higher stimulation frequencies and preloads result in a more quickly contracting muscle, which generates more pressure. Midrange stimulation frequencies of 30 Hz provide optimal muscle strength and minimize time to develop peak pressure. Initiation of contraction should begin before the time maximal pressure is desired.

Skeletal muscle ventricles in continuity with the bloodstream.

BACKGROUND AND AIM OF STUDY: The prevalence of end-stage congestive heart failure and limitation of clinical alternative treatments present the need for creative new solutions. Formation of a ventricle from skeletal muscle (SMV) has shown promise in the animal laboratory. Two modes of the SMV for cardiac assistance, the counterpulsation (CP-SMV) and the ventricular assist (VA-SMV), using the latissimus dorsi muscle were applied in a canine model. Ability to augment arterial pressure was assessed. The effect of stimulation delay on the degree of augmentation was also evaluated. METHODS AND RESULTS: Thirty-five SMVs were connected in continuity with the bloodstream in the two modes: (1) CP-SMV (aorta-to-aorta) (n = 12); and (2) VA-SMV (left ventricular [LV] apex-to-aorta) (n = 23). In the CP-SMV mode, designed to simulate the intra-aortic balloon pump, the SMV was simply interposed into the path of the descending aorta (DAo) without prosthetic valves in either the inflow or the outflow conduit. In order to obligate blood flow through the SMV, the DAo was ligated between the two grafts. In the VA-SMV mode, the connection was made with valved conduits from the LV apex (inflow) to the ascending aorta (outflow) (n = 11) or to the DAo (n = 12). The ascending aorta (AAo) was also ligated proximal to the outflow conduit for the same reason of obligating blood flow through the SMV. The SMV was timed to contract in diastole in both the CP-SMV mode and the VA-SMV mode. In the VA-SMV mode, the average systolic pressure without stimulation was 101.6 +/- 2.2 mmHg and with stimulation 118.21 +/- 4.78 mmHg (mean augmentation, 14.5 +/- 2.6 mmHg) (p < 0.01). In the CP-SMV mode, the average systolic pressure without stimulation was 97 +/- 32 mmHg and with stimulation, 122 +/- 26 mmHg (mean augmentation, 25 +/- 8.6 mmHg) (p < 0.001). We also extended earlier work on timing of stimulation of isolated SMV by evaluating the effect of stimulation delay on the degree of augmentation in continuity with the bloodstream with the SMV in the VA-SMV configuration. Delays of 50 msec to 225 msec were evaluated. SMV stimulation was via the thoracodorsal nerve at an amplitude of 1.5 V and a frequency of 25 Hz. The greatest augmentation occurred at a stimulation delay of 150 msec (p < 0.001). CONCLUSION: Both counterpulsation and assist configurations produced effective diastolic augmentation. Although diastolic augmentation occurred with all timing delays, the optimal delay was 150 msec. Complications in the survival animals include AAo problems, SMV rupture, respiratory insufficiency, intraoperative instability, and thrombosis (which occurred in 51% [18/35] of the animals). This high frequency of thrombosis in the canine model suggests the use of a less thrombogenic SMV lining, more aggressive or prolonged anticoagulation, or an alternative animal model.

Posterior tibial tendon dysfunction and MRI.

Posterior tibial dysfunction can lead to disabling weightbearing symptoms and progressive pes planovalgus deformity. The different types of pathology are reviewed and three case reports are presented in this article. The use of magnetic resonance imaging (MRI) in diagnosing and in treatment planning is discussed, and emphasis is made for MRI as the preferred study for posterior tibial dysfunction.

Comparison of 180-degree and 360-degree skeletal muscle nerve cuff electrodes.

Use of skeletal muscle for cardiac augmentation is a promising technique for treatment of end-stage cardiac failure. An electrode woven through the latissimus dorsi that recruits nearby nerve fibers is commonly used to pace skeletal muscles both in clinical practice and in the laboratory. A proximally placed nerve cuff electrode offers potential advantages in improved recruitment of muscle fibers and low threshold for stimulation. We tested the effectiveness of a nerve cuff electrode passed directly about the proximal thoracodorsal nerve. Our report looks at the efficacy of nerve cuff electrode stimulation and compares electrical and histologic characteristics of a 180-degree wrap of the thoracodorsal nerve to a 360-degree wrap in dogs over 3 months. Threshold voltage at the commonly used pulse width of 200 microseconds was typically in the range of 400 to 600 mV for each electrode after 3 months. Statistical analysis revealed no significant difference (p < 0.05) in threshold voltage or current between the 180-degree and 360-degree nerve cuff electrode either at acute evaluation or after 3 months. Even contraction of latissimus dorsi was achieved with all implants. Adenosine triphosphatase staining revealed 100% conversion of type II to type I fibers in all stimulated muscles. Histologic examination of the thoracodorsal nerve and latissimus dorsi muscle revealed no abnormalities grossly or by light microscopy. Thus, a carefully applied nerve cuff electrode is an atraumatic, effective method for skeletal muscle stimulation. The 180-degree and 360-degree nerve cuff configurations are equally effective.

Electrical techniques for stimulation of the phrenic nerve to pace the diaphragm: inductive coupling and battery powered total implant in asynchronous and demand modes.

A review of the electrical design of a rf inductively coupled phrenic nerve stimulator for the diaphragm developed in our laboratories will be discussed. Modifications of the original circuit are based on long-term laboratory and clinical studies. A total implant battery powered stimulator was designed exclusively for animal studies to evaluate the effects of several stimulating parameters on diaphragm fatigue and neuromuscular structure. On the basis of these studies the optimum current level, stimulus frequency, respiratory rate, electrode configuration, and waveform were selected for clinical use to pace the diaphragm. A multiprogrammable dual output stimulator responsive to interrogation has been constructed and used in the experimental laboratory in anticipation of clinical application. There was an insignificant difference between the effect on neural structure or diaphragm function of stimulation with pulse width modulated constant voltage or with amplitude-modulated constant current. Demand pacing: maintenance of normal PACO2 by monitoring ET PACO2 with feedback to the diaphragm pacemaker to adjust the pacing rate has been successful in the experimental animal.

Ventilatory support by pacing of the conditioned diaphragm in quadriplegia.

We provided full-time ventilatory support in five patients with respiratory paralysis accompanying quadriplegia by continuous electrical pacing of both hemidiaphragms simultaneously for 11 to 33 months through the application to the phrenic nerves of a low-frequency stimulus. The strength and endurance of the diaphragm muscle increased with pacing. Biopsy specimens taken from two patients who had uninterrupted stimulation for 6 and 16 weeks showed changes suggestive of the development of fatigue-resistant muscle fibers. When we compared these results with those of our earlier experience with intermittent unilateral stimulation of the diaphragm in 17 patients with respiratory paralysis, we found that continuous bilateral pacing using low-frequency stimulation appeared to be superior because of more efficient ventilation of both lungs, fewer total coulombs required to effect the same ventilation, and absence of myopathic changes in the diaphragm muscle. For patients with respiratory paralysis and intact phrenic nerves, continuous simultaneous pacing of both hemidiaphragms with low-frequency stimulation and a slow respiratory rate is a satisfactory method of providing full-time ventilatory support.

Response of the diaphragm muscle to electrical stimulation of the phrenic nerve. A histochemical and ultrastructural study.

The histological, histochemical, and ultrastructural features of canine diaphragms subjected to pacing by high-frequency electrical stimulation (27 to 33 Hz) of the phrenic nerve are compared with unstimulated diaphragms and with diaphragms subjected to pacing by low-frequency stimulation (11 to 13 Hz). The high-frequency group showed a reduced tidal volume (fatigue) after long-term stimulation, and myopathic changes which included enlarged internal and sarcolemmal nuclei, ring fibers, moth-eaten fibers with irregular histochemical staining, core/targetoid fibers, and smearing and aggregation of Z-band material with electron microscopy. The low-frequency group did not develop a significant degree of fatigue or pathological changes, and showed histochemical evidence of transformation to fast-twitch (type II) fibers. Possible pathogenic mechanisms and their similarity to those in certain human neuromuscular diseases are discussed. The application of the findings resulting from high- and low-frequency stimulation to long-term diaphragm pacing in humans with chronic ventilatory insufficiency is also discussed.

Light and electron microscopic studies of phrenic nerves after long-term electrical stimulation.

Light and electron microscopic evaluation were carried out on canine phrenic nerves subjected to long-term electrical stimulation. A total of 34 stimulated and 19 control nerves were studied by light microscopy, and 10 stimulated and five control nerves were evaluated by electron microscopy. Except in a few cases in which a higher current was used, the current used for stimulation was between 1 and 2 mA. The pulse width was 150 microseconds. The typical charge per pulse was 0.22 microC and charge density per pulse 1.125 microC/sq cm of real area. The total number of days of electrical stimulation in individual phrenic nerves ranged from 4 to 374. No morphological changes in the phrenic nerve that could be attributed to the electrical stimulation were observed by light or electron microscopic study. There were, however, two phrenic nerves cuffed with bipolar electrodes which showed focal demyelination at the electrode level, but these changes were caused by factors other than the electrical stimulation. The results of the studies have direct clinical implications to long-term stimulation of phrenic nerves.

Electrophysiological evaluation of phrenic nerve function in candidates for diaphragm pacing.

The electrophyisological status of phrenic nerve function has been determined by an assessment of the conduction time and diaphragm muscle action potential in patients who were being evaluated as candidates for diaphragm pacing, or who were being studied for suspected phrenic nerve injury or disease. The conduction time and muscle action potential were evoked by transcutaneous phrenic nerve stimulation or by stimulation with a permanently implanted diaphragm pacemaker. In normal volunteers the conduction time was found to be 8.40 msec +/- 0.78 msec (SD). Transcutaenous phrenic nerve stimulation was successful in predicting phrenic nerve viability in 116 of 120 nerves studied. The four false negatives were due to technical difficulty in locating the nerves in obese or uncooperative subjects. In patients who were selected for implantation of a diaphragm pacemaker, a conduction time that was prolonged (10 to 14 msec) preoperatively did not preclude successful diaphragm pacing. Postoperatively, a prolonged (> 10 msec) conduction time was associated with severe systemic disease or local nerve injury caused by trauma or infection. The elucidation of phrenic nerve function by such electrophysiological studies serves as a valuable adjunct to the selection and management of patients undergoing diaphragm pacing.

Diaphragm pacing. Evaluation of current waveforms for effective ventilation.

To evaluate the effectiveness of the configuration of the stimulating waveform on diaphragm pacing, we evaluated several different current forms: UDC-bipolar, UDC-monopolar cathodal, UDC-monopolar anodal, and ABDC. During stimulation with a pulse interval of 37 msec., a decrease in tidal volume was observed during the initial 30 hours with UDC-bipolar and UDC-monopolar anodal waveforms. Both UDC-monopolar cathodal and ABDC stimulation maintained the initial effectiveness for 6 hours. The decrease in tidal volume of UDC-monopolar anodal closely paralleled that of UDC-bipolar stimulation. Decreasing the pulse interval to 20 msec. caused a decrease in tidal volume with both UDC-monopolar cathodal and ABDC waveforms. Arterial oxygen tension (PaO2) in these experiments decreased to about 60 mm. Hg soon after the onset of unilateral diaphragm pacing. The concomitant decrease in tidal volume seen with UDC-bipolar stimulation could be avoided through the administration of oxygen to keep the animal's PaO2 about 100 mm. Hg. The amplitude of the evoked diaphragmatic action potentials decreased significantly under hypoxemia and returned to normal with hyperoxygenation. From these short-term experiments, our findings indicate that waveform configuration does influence the time of onset of diaphragm fatigue due to either an neuromuscular junction. Further, hypoxemia accelerates the occurrence of fatigue.

A demand diaphragm pacemaker.

A PACO2 feedback control system (demand diaphragm pacemaker) was developed in this laboratory to maintain homeostasis during diaphragm pacing, thus avoiding hypo- or hyperventilation. Application of this system to the research animal made it possible to maintain blood gases and pH within normal limits for up to 15 hrs. Oscillation between maximal tidal volume and apnea that occurred with the amplitude feedback control was eliminated by using a rate feedback control. A possible additional benefit of a feedback control system is the reduction of current applied to the nerve as compared to that in asynchronous pacing, thereby minimizing the fatigue phenomenon.

Long-term ventilatory support by diaphragm pacing in quadriplegia.

Thirty-seven quadriplegic patients with respiratory paralysis were treated by electrical stimulation of the phrenic nerves to pace the diaphragm. Full-time ventilatory support by diaphragm pacing was accomplished in 13 patients. At least half-time support was achieved in 10 others. There were two deaths unrelated to pacing in these two groups. Fourteen patients could not be paced satisfactorily, and 8 of these patients died, most of them from respiratory infections. The average time the 13 patients on total ventilatory support have had bilateral diaphragm pacemakers is 26 months. The longest is 60 months. Many of these patients are out of the hospital and several are in school or working. Injury to the phrenic nerves either by the initial trauma to the cervical cord or during operation for implantation of the nerve cuff was the most significant complication. Nerve damage from prolonged electrical stimulation has not been a problem thus far. A description of the pacemaker, the technique of its implantation, and the pacing schedule are reported.