THERAPY APPARATUS FOR THE FUNCTIONAL ELECTROMYOSTIMULATION OF SMOOTH MUSCLE CELLS

Abstract: The subject of the invention is an apparatus for the functional electromyostimulation of smooth muscle cells for the therapy of disturbances of the smooth muscle cell function, especially in the case of erectile dysfunction and incontinence in the case of humans and mammals.

Description: Therapy apparatus for the functional electromyostimulation of smooth muscle cells Description The invention concerns a therapy apparatus for the functional electromyostimulation of smooth muscle cells, especially of the penis and of the urethra and their connective tissue within the human body by meens of which a regeneration of the smooth muscles and thus a functional improvement of the diseased cell connective tissues and organs is achievable. Treatments of disturbances, such as e.g. certain forms of erectile dysfunction or incontinence, are therewith possible which otherwise cannot be achieved with the apparatus and aids at present available. In the case of the incidence of e.g. 3 to 4 million men in Germany with chronic erectile dysfunction, there is a great medicinal importance for the principally possible therapeutic options. At the present point of time, the corpus cavernosum autoinjection therapy (CCAT; 1 - 5) , the penis prosthesis implantation (6 - 8) or the use of a vacuum system form the cornerstones of the therapy of organogenic erectile dysfunction. However, because of the absence of spontaneity, of possible side effects or af the non-physiological manner of working, many patients refuse these treatment alternatives from the onset, Furthermore, high drop-out rates or a considerable number of dissatisified users are to be ascertained in the long-term observation (5) . As alternative, for these patients there is only available the reconstructive penile blood vessel surgery (9, 10) which, however, only comes into question for selected patients because of the complex aetiology of the erectile dysfunction. In recent electron microscopic studies, it could be shown that, in the case of many patients, a degeneration of the cavernous smooth muscles is present as cause of the erectile dysfunction (11 - 13) . In the case of these patients, as therapy possibilities only the prosthetic provision of the vecuum aid comes into question. Possibilities of the regeneration of these cavernous smooth muscle cells which make possible substantially more therapeutic options for the affected patients are, however, hitherto not known. In the case of patients in the case of which, because of a temporary inactivation of the skeletal musculature, e.g. by application of a plaster in the case of fractures, or of the temporary lesion of muscle-innervating nerves after accidents or operations, it results in an atrophy of the musculature with the known disadvantageous results, for the evoidance of this atrophy during the resting or lesion phase, transcutaneous stimulation current can be applied. This process represents a standard method (14 - 17) in the treatment or prophylaxis of atrophies of the skeletal or striated musculature. Because of the poor accessibility of the organs consisting of smooth muscle cells (e.g. oesophagus, uterus, urethra, urinary bladder) , the thereby poor delimitation from other organs and the fundamentally different stimulation of the smooth muscle cells in contradistinction to striated muscle cells, no possibilities exist to influence these organs by means of transcutaneously applied current. Our own hitherto unpublished investigations on isolated corpus cavernosum tissue have, surprisingly, now shown that the smooth musculature of the penile corpus cavernosum has a phase electrical activity of about 20 hz. Furthermore, our own hitherto unpublished investigations on patients with erectile dysfunction showed that, in the case of many of these patients, a partial denervation of the penile corpus cavernosum is present as cause of the erectile disturbance. This surprisingly, completely new and unexpected knowledge now justifies the use of transcutaneously applied current for the regeneration of the smooth musculature of the penile corpus cavernosum as treetment possibilities of the erectile dysfunction. An inventive stipulation for the feasibility of such therapies is the arranging of the therapy apparatus in such a way that it is battery-, accummulator- or mains-operated and that the arrangement of the stimulation takes place in such a way that via, in each case, one or more skin electrodes on both sides laterally of the penile shaft, the stimulation can take place directly via a one- or two-channel amplifier or via the small of the back. A further inventive stipulation for the feasibility of such therapies in the arranging of the therapy apparatus in such a way that the arranging of the stimulation parameters takes place in such a manner that it permits zero line-symmetrical impulses of rectangular or trapezium form with a build-up time of 0,01 to 2 seconds, a stimulation period of 1 to 60 seconds direct or alternating, a stimulation pause of 0,01 to 60 seconds, a frequency range of 1 to 50 Hertz and an impulse period of 100 μs to 10 ms or a specifically defined subgroup of the above-mentioned parameters. The stimulation of the muscle cells takes place via surface electrodes which can be usable one or more times or via needle- or intraurethrally-applicable electrodes usable one or more times. Furthermore, the possibility exists to store and afterwards to retrieve the treatment times and the employed parameters by storage possibilities within or outside of the device. The results of such therapy procedures with the therapy apparatus according to the invention are shown in the following: The therapy apparatus according to the invention was used on 22 patients with erectile dysfunction in which otherwise no reconstructive therapy procedures have produced success. All patients were sworn to secrecy with regard to this treatment process. A satisfactory therapy result could be achieved in the case of 8 of these 22 patients. The following Tables give exact information regarding the patient groups, which were broken down according to the treatment success: Table 1 Patients after FEMCC and completely spontaneous erection after FEMCC name anamnesis CC-EMG Doppler MF R.P. prolaps L4/5 n P 60 K.S. hypertension n n 150 W.B. - n n 10 S.M. failure anxiety n n - R.S. diabetes I, time n P 8 after Hauri op n = normal p = pathological MF = maintenance flow in ml/minute measured during the pharmacocavernosometry Table 2 Patients after FEMCC and and positive CCAT-Test after FEMCC name anamesis CC-EMG Doppler MF H.B. ped n P 10 T.B. P n 40 G.M. diabetes I P P 10 n = normal p = pathological MF = maintenance flow in ml/minute measured during the pharmacocavernosometry ped = primary erectile dysfunction Table 3 Failure on FEMCC name anamesis CC-EMG Doppler MF E.M. — P P 60 H.N. 2 x A.I. pelv. # n n 60 W.L. DM II, MI, AA P P 80 A.E. pelv. # P n not done H.L. ped, VA, AR, VL n n 8 G.S. DM I, VL P n 80/7 D.G. AR P P 4 B.W. A.I. NTx n P 200 K.A. ALL P n 38 D.N. DM II, Hyp P n 20 R.H. ped P P 80 K.K. VL n n 45/30 E.R. ped P n 50 M.P. dialysis P n 80 ped = primary erectile dysfunction A.I. = apoplexy pelv. # = pelvis fracture with urethral avulsion DM = diabetes mellitus MI = infarct AA = absolute arrhythmia VA = failure anxiety AR = post-penile arterialisation VL = post-penile vein surgery ALL = acute lymphatic leukaemia Hyp = hypertension n = normal p = pathological MF = maintenance flow Therefore, the therapy apparatus according to the invention consists of needle or surface electrodes, a mobile or stationary apparatus for the stimulation of smooth muscle cells with stimulation possibilities which permits zero line- symmterical impulses of rectangular or trapezium form with a build-up time of 0.01 to 2 seconds, a stimulation period of 1 to 60 seconds direct or alternating, a stimulation pause of 0.01 to 60 seconds, a frequency range of 1 to 50 Hertz and an impulse period of 100 μs to 10 ms or a specifically defined sub-group of the above-mentioned parameters. Some additional aspects and possibilities in accordance with the invention are as follows. In one exemplary methodology, patients with chronic erectile dysfunction may receive daily (3 to 5 times; 20 min per event) transcutaneous functional electromyostimulation of the corpus cavernosum smooth muscles ("FEMCC") : for example, zero-line symmetric impulses of trapezoid shape, 2-channel device with alternating stimulations; frequency (f) , 10-20 Hz for channel 1 and 20-35 Hz for channel II; impulse duration (t-±) , 100-150 μs; approx. 12 mA; rise time, 0.5 s; stimulation time, 5 s/channel; pause between stimulations 0.5 s. Responsive patients might either regain full spontaneous erections or become responsive to vasoactive drugs after FEMCC. One main aspect of the invention is to utilize the effect of transcutaneaus functional electromyostimulation of the corpus cavernosum smooth muscles (FEMCC) in patients with erectile dysfunction. All patients are preferably subjected to a comprehensive approach regarding the etiology of their erectile dysfunction. This approach includes a case history, physical examination, blood laboratory workup, sexual case history (done by a psychiatrist) , corpus cavernosum electromyography (CC-EMG) pharmacotesting, and Doppler. When indicated patients may be subject to further examinations such as cavernosometry and cavernosography, penile angiography, or so aromotoric and/or autonomic neurological examinations. In the case of patients who do not respond to maximal doses of intracavernous injections (30 mg papaverine plus 1 mg phentolamine) plus additional psychogenic or reflexogenic stimulation they are considered as having a high likelihood of venous leakage as a (co)factor for their erectile dysfunction. Since CC-EMG has been found to be an important prognostic factor for penile venous surgery, only those patients who fail to respond to vasoactive drugs and who do not have a normal CC- EMG finding are appropriate candidates to undergo cavernosometry and cavernosography and, possibly, venous surgery. Nonresponders with abnormal CC-EMG findings will most likely have autonomic neuropathy and/or cavernous smooth-muscle degeneration and are therefore unsuitable candidates for reconstructive surgery. For these patients other therapeutic strategies are advised, such as vacuum devices, penile prosthesis, or a trial with intracavernous injection of a combination af calcitonin-gene-related peptide (CGRP) plus prostaglandin El (PGE1) . Nonresponders with abnormal CC-EMG findings as well as patients who were unwilling to accept other treatment options are favorable candidates for FEMCC as an alternative treatment for their erectile dysfunction. The electrodes are placed preferably with two electrodes placed bilaterally over the penile shaft and connected in such a way that a diagonal current is achieved. Four electrodes are preferably connected to a battery-operated stimulator (two channels) designed for diagonal alternating stimulation and the stimulation parameters are established (for example: zero-line symmetric impulses of trapezoid shape; two-channel device with alternating stimulations; rise time 0.5 s; stimulation time; 5 s; pause between stimulations, 0.5 s) . The frequency may be modified individually according to the patient's perception (ranges freqency (f) , 10-20 Hz for channel I and 20-35 Hz for channel II; impulse duration (t-^) , 100-150 μs) until a sensory perception of current (approximately 12 mA is reported. Patients preferably undergo stimulation three to five times daily, with each treatment session lasting for at least 20 minutes. There may be a slight chance of a placebo effect whenever daily treatment sessions are conducted over a longer period. Nonetheless, most of the therapeutic effect observed after FEMCC is thought to be due to a regeneration of the cavernous smooth-muscles. In the treatment of smooth-muscle denervation and subsequent smooth-muscle atrophy transcutaneous application of low- Frequency electric current has not been used, to the best af our knowledge. Although erectile dysfunction is a multifactorial event, with many psychic and organic factors playing an imporcant role, the intactness of the cavernous smooth-muscle cells is a key requisite for the erectile process. The regeneration of the cavernous smooth-muscle cells induced by transcutaneous applications of low-frequency electric current should result either in a regain of spontaneous erectile capacity, if no other factor is involved in the etiology of the erectile dysfunction, or in a response to the intracavernous injection of vasoactive drugs if other factors, e.g. autonomic neuropathy, are involved. The parameters of the electric current applied in the present study are based on both experimental findings and deductions from the therapy of striated muscles. A frequency range of 10- 35 Hz is preferred since these frequencies are thought to induce the best ereccile response when direct neurostimulation is applied to the cavernous nerve. Different frequency ranges for channels I and II were chosen in accordance with experiences in striated muscle rehabilitation, where different frequencies stimulate different groups of muscle cells, thus resulting in a better overall response. An impulse duration of 100—150 μs was preferable since such an impulse width does not typically provoke pain or discomfort. The parameters described herein will stimulate regeneration only of cavernous tissue with intact or partially intact autonomic supply. The electric current generated as described will induce a discharge of synaptic information, resulting in ("indirect") changes in the cavernous smooth-muscle regeneration. Such circumstances may explain a relatively low success rate (of 33%) with some patients. For the possible achievement of higher rates of success, direct electrical stimulation of the cavernous smooth-muscle cells is an approach, for example using different stimulation parameters of f , 1-5 Hz ; t χ , 1-10 ms . In general, FEMCC is feasible and results in an improvement in erectile capacity in a significant number of patients. List of Citations (1) Virag R. (1982) Intracavernous injection of papaverine for erectile failure. Letter to the editor. Lancet 2: 938 (2) Brindley G.S. (1983) Cavernosal alpha-blockade: a new technique for investigating and treeting erectile dysfunction. Brit. J. Psychiatr. 143: 332-337 (3) Zorgniotti A.W. and Lefleur R.S. (1985) Auto-injection of the corpus cavernosum with a vasoactive drug combination for vasculogenic impotence. J. Urol. 133: 39-43 (4) Ishii N. , Watanabe H. , Irisawa C. (1989) Intracavernous injection of prostaglandin El for the treatment of erectile impotence. J. Urol. 141: 323-327 (5) Junemann K.P. and Alken P. (1989) Pharmacotherapy of erectile dysfunction. Int. J. Impotence Res. 1: 71-85 (6) Scott F.B., Bradley W.E., Timm G.W. (1973) Management of erectile impotence. Urology 2: 80-85 (7) Small M.P., Carrion H.M., Gordon J.A. (1975) Small-Carrion penile prosthesis. Urology 5: 479-484 (8) Montague D.K. (1989) Penile prosthesis. An overview. Urol. Clin. N. Amer. 16: 7-17 (9) Levine F.J., Gasior B.L., Goldstein I. (1989) Reconstructive arterial surgery for impotence. Sem. Interven. Radiol. 6: 220-229 (10) Goldstein I. (1987) Penile revascularisation. Urol. Clin. N. Amer. 14: 805-812 (11) Persson C. , Diedrichs W. , Lue T.F., Yen T.S., Fishman I., Mc. Lin P.H., Tanagho E.T. (1985) Correlation of altered ultrastructure with clinical arterial evaluation. J. Urol. 142: 1462-1467 (12) Wetterauer U. , Stief C.G., Kulvelis F. , Staubesand, Sommerkamp H. (1990) The electron microscope ultrastructure of cavernous tissue in erectile dysfunction. J. Urol. 143: 509A (13) Mersdorf A., Goldsmith P., Diederichs W. , Padula C. , Lue T.F., Fishman I., Tanagho E.T, (1991) Ultrastructural changes in impotent penile tissue. J. Urol. 145: 749-754 (14) ; Edel H. (1977) Fibel der Elektrodiagnostik und Elektrotherapie, Verlag Theodor Steinkopf, Dresden (15) Taylor P.N., Ewins D.J., Fox B. , Grundy D. , Swain I.D. (1993) Limb blood flow, cardiac output and quadriceps muscle bulk following spinal cord injury and the effect of training for the Odstock functional electrical stimulation standing system. Paraplegia 31: 303-309 (16) Trimble M.H., Enoka R.M. (1991) Mechanisms underlying the training effects associated with neuro uscular electrical stimulation. Phys. Ther. 71: 273-281 (17) Delitto A., Snyder-Mackler L. (1990) Two theories of muscle strength augmentation using percutaneous electrical stimulation. Phys. Ther. 70: 158-165

Claims: Claims 1. Therapy apparatus for the electrical stimulation of smooth muscle cells by means of electrodes, characterised in that the therapy apparatus is battery-, accummulator- or mains- operated. 2. Therapy apparatus according to claim 1, characterised in that the stimulation takes place in such a manner that, via one or more skin electrodes on both sides laterally of the penile shaft, the stimulation can take place directly vis a one- or two-channel amplifier or via the small of the back. 3. Therapy apparatus according to claim 1, characterised in that the stimulation of the muscle cells takes place via surface electrodes which can be usable one or more times or via needle- or intraurethrally-applicable electrodes usable one or more times. 4. Therapy apparatus according to claims 1 to 3, characterised in that there can be applied zero line-symmetrical impulses of rectangular or trapezoid form with a build-up time of 0,01 to 2 seconds, a stimulation period of 1 to 60 seconds direct or alternating, a stimulation pause of 0,01 to 60 seconds, a frequency range of 1 to 50 Hertz and an impulse period of 100 μs to 10 ms or a specifically defined sub¬ group of the above-mentioned parameters. 5. Therapy apparatus according to claims 1 to 4, characterised in that storage possibilities store the treatment times and the parameters used within or outside of the apparatus and these are afterwards retrievable. 6. Therapy apparatus for the treatment of penile erectile dysfunction and/or incontinence utilizing the effect oft transcutaneous functional electromyostimulation of the corpus cavernosum smooth-muscles for the regeneration of such cavernous smooth muscles. 7. Therapeutic methodology for the treatment of penile erectile dysfunction and/or incontinence utilizing the effect oft transcutaneous functional electromyostimulation of the corpus cavernosum smooth-muscles for the regeneration of such cavernous smooth muscles.

Inventors: NOACK THOMAS, STIEF CHRISTIAN, WELLER EDGAR, NOACK, THOMAS, STIEF, CHRISTIAN, WELLER, EDGAR
Applicants: NOACK THOMAS, OSBON MEDICAL SYSTEMS, STIEF CHRISTIAN, WELLER EDGAR, NOACK, THOMAS, STIEF, CHRISTIAN, WELLER, EDGAR
Application year: 1996
Main classification: A61N1
IPC codes: A61N1