IL118968A - Apparatus for biostimulation of myocardial tissue by electromagnetic wave radiation - Google Patents

Abstract

Apparatus for biostimulation by electromagnetic wave radiation of a myocardial tissue comprising: an electromagnetic wave radiation transducer (12) which communicates with a source (14) of electromagnetic wave radiation via at least one optical fiber, said electromagnetic wave radiation transducer being operative to irradiate an infarct (10) of a myocardium (18) after insertion of said at least one optical fiber through a catheter into a ventricle, an echo transducer (20) which communicates with an echo imaging device, said echo transducer being operative to provide positional information of said infarct, and a fastener (24) which fastens said electromagnetic wave radiation transducer together with said echo transducer and which substantially maintains said transducers in a fixed spatial relationship with each other.

Description

APPARATUS FOR BIOSTIMULATION OF MYCOCARDIAL TISSUE BY ELECTROMAGNETIC WAVE RADIATION BIOSENSE C: 25075 APPARATUS FOR BIOSTIMULATION OF MYOCARDIAL TISSUE BY ELECTROMAGNETIC WAVE RADIATION FIELD OF THE INVENTION The present invention relates to cardiology generally, and particularly to apparatus for improvement of heart function and eliminating scar tissue formation and for regeneration of myocardial tissue following myocardial infarction, or other heart failure syndromes by using electromagnetic wave radiation to cause biostimulation.

BACKGROUND OF THE INVENTION Heart disease or heart failure following myocardial infarction is still the major cause of death in the western world. The mature heart muscle (myocardium) cells of mammals are those that reach their last stage of differentiation and, therefore, are considered unable to undergo proliferation (see P.P. Rumynastev. Growth and Hyperplasia of Cardiac Muscle Cells. B.M. Carlson, ed., Harwood, New York, 1991, pp. 3-68) . Thus, the myocardium may be afflicted with hypertrophy (increase in cell mass and not cell number) due to mechanic stress or ischemia (inadequate oxygen supply to the cells) . Following ischemia, due to occlusion of blood supply to the cells during myocardial infarction (MI), irreversible, physiological changes occur in the cells which degenerate and are replaced by non-contracting scar tissue (infarcted zone) with time (see M.C. Fishbein, M.B. McLean et al.

Experimental myocardial infarction in the rat. Am. J.

Pathol. 90: 57-70; 1978) .

The clinical treatments of acute MI include thrombolytic treatment (W. Ganz, N. Buchbinder, H. Marcus et al. Intracoronary thrombolysis involving myocardial infarction. Am. Heart 101: 4-10; 1983), PTCA (coronary angioplasty) performed on occluded arteries (A.R. Gruentzig et al. Long-term follow-up after percutaneous transmural coronary angioplasty. N. Engl. J. Med. 316: 1127-32; 1987) and also bypass surgery as near as possible to the occurrence of the MI (G.M. Fitzgibon, A.J. Leach, H.P. Kafka et al.. Coronary bypass graft fate: long-term angiographic study. J. Am. Coll. Cardiol. 17: 1075-80; 1991). These procedures are expensive, demand very qualified personnel and physicians, and are not always practically possible in health care. Moreover, these methods endeavor to alter the consequences of the irreversible ischemic injury that occurs in the cells rather than inhibit such consequences. It should be mentioned that even with qualified personnel and first-rate treatment, the above procedures are not always successful.

Several attempts have been made in the past to reduce the infarcted area in the myocardium following induction of MI in experimental animals. These include the use of corticosteroids, various antioxidant agents, etc.

Low energy laser irradiation has recently been found to modulate various processes in different biological systems (see M. Belkin, B. Zaturunsky, and M. Schwartz. A critical review of low power laser bioeffects. Laser Light Ophthalmol. 2: 63-71; 1988, and T. Karu. Photobiology of low power laser effects.

Health Phys. 56: 691-704; 1988). For example, in isolated 2 mitochondria, He-Ne laser irradiation (5 J/cm ) elevated membrane potential and production of ATP, while in isolated fibroblasts with the same radiation, an increase in collagen production was observed. The effect of low energy laser irradiation on regeneration processes following trauma has thus far been investigated in the skin, the peripheral nervous systems, skeletal muscles and bone. It has been found that laser irradiation given at the right time and energy level modulates the process of regeneration and, in most systems, causes a faster recovery after trauma and an enhanced rate of regeneration ( see N. Weiss and U. Oron. Enhancement of muscle regeneration in the rat gastrocnemius muscle by low energy laser irradiation. Anat Embryol. 186: 497-503; 1992, and 0. Barushka, T. Yaakobi and U. Oron. Effect of laser irradiation on the process of bone repair in the rat tibia. Bone 16: 47-55; 1995).

In a recent study, the effect of irradiation of the blood (subclavian artery) by He-Ne lasers in patients after MI was observed (see N.N. Kipshidze et al., Intravascular laser therapy of acute myocardial infarction, Angiology 801-808; Sept. 1990). The study reports a better recovery of the laser irradiated patients in terms of the levels of enzyme activity (creatine phosphokinase ) in blood (which was lower in the irradiated patient) and a reduction of arrhythmia of the heart.

It is to be emphasized that the Kipshidze et al. paper does not teach biostimulation of the myocardium itself but rather of the blood. The authors write in the Abstract "A new method for ... using monochromatic He-Ne laser ... this paper deals with the effect of endovascular (inside blood vessels) laser blood irradiation on high-grade arrhythmias". On page 802, lines 2 - 3, it states that "Endovascular laser therapy was performed using an LG-75 laser via an optical light guide introduced into the lumen of the superior vena cava...". Thus, the myocardium was not irradiated but rather blood.

It is known in the art (see Mester, A.R., Modalities of low power laser applications, Galletti et al. (eds. ) Laser Applications in Medicine and Surgery, Monduzzi Editore (1992), pp. 33-40) that the energy emitted from a He-Ne laser, even with high energy, is absorbed by hemoglobin in the red blood cells and by living tissues. This type of energy at the specific wavelength (632.2 nm) does not penetrate well through living tissues. The loss in energy output is about 90% after 2 mm depth of tissue and there is practically no energy capable of penetrating beyond 3 mm depth of tissue with a moderate blood supply. It is also acknowledged in the art that exposure of the tissue to energy less than 4mW has no biostimulatory effect on tissues (see Galletti et al. ibid, and Bradley, P.F. and B. Gursoy, Penetration studies of low intensity laser therapy (LILT) wavelength, Proc. WALT 1996, p. 18.).

Thus, when energy from the He-Ne laser source (the energy power is not cited in the Kipshidze et al. work, but can be at most 40 mW) is conveyed through an optical fiber (which causes a loss of approximately 30-40% of the source), it ends up at the tip of an optical fiber at no more than 25 mW. Since the tip is situated in a blood vessel (superior vena cava) which is at least 5 cm in distance from the heart muscle, the energy which is absorbed by the heart muscle from the optical fiber is practically zero and has no biostimulatory effect on the heart muscle based on the above scientific knowledge.

Other studies have reported qualitative alternations in the ultrastructure of musculature (see Ruzov, I.V. and Baltrushaitis, K.S., Ultrastructural changes in the myocardium under the action of the helium-neon laser and obzidan, Vopr. Kurotol. Fizioter. Lech. Fiz. Kult. 5-6: 62-64 1992), blood vessels (see Ruzov, I.V. and Baltrushaitis, K.S., The microcirculator bed of the ischemic myocardium under the combined action of a low-intensity helium-neon laser and finoptin, Vopr. Kurotol. Fizioter. Lech. Fiz. Kult. 4: 31-3; 1993) and mitochondria of the myocardium of rabbits in a hypodynamic stage following irradiation of the blood by He-Ne laser (see Ruzov, I.V. and Rishkus, L.A., The effect of the helium-neon laser on the cyclic nucleotide level in experimental hypodynamia, Vopr. Kurotol. Fizioter. Lech. Fiz. Kult. 2:51-53; 1992). The irradiation in the above studies was performed by insertion of fiber optics through the ear vein in the ear of the rabbits. It should be emphasized that in the Russian Republic, irradiation of blood by UV or low energy lasers is a common procedure towards a better recovery in many human illnesses (see Ruzov, I.V. A comparative study of the action of the helium-neon laser, perlinganite and heparin on the energy apparatus of the ischemic myocardium. Vopr. Lech. Fizioter. Lech. Fiz. Kult. 1 : 33-35 ; 1994).

In the four aforementioned scientific papers by Ruzov et al., the authors use an experimental system of He-Ne laser at power energy of 1.5 mW, similar to Kipshidze et al. Again, the energy was introduced by fiber optics into a blood vessel, this time into a vein in the ear of a rabbit. As mentioned above with reference to the paper by Kipshidze et al., the energy that will finally be transmitted from the vein in the ear to the heart muscle is practically zero without any expected biostimulatory effects on ischemic or hypodynamic heart muscle as mentioned in these scientific papers.

Russian Patent 1715351 to Golikov et al., relates to irradiation treatment by a He-Ne laser at acupuncture points to help recovery of heart disease in the post-infarction period. However, this patent can not relate to irradiation of the myocardium because the He-Ne laser beam, even if aimed at points on the chest of a human patient above the heart, cannot penetrate more than 2 - 3 mm. Thus, practically no laser energy can reach the heart muscle since the muscle between the ribs in humans is at least 1 cm thick. The positive effects achieved in laser irradiated patients, is perhaps due to acupuncture treatment or reflexogenic therapy, as cited by the authors themselves in the last paragraph of the patent.

Russian patent 2022574 to Aleshin et al., relates to devices for physiotherapeutic treatment with laser and infrared radiation in combination with a magnetic field. RU 2022574 discloses apparatus containing a terminal with a pulsed semiconductor laser emitter, a constant magnetic field source, light-emitting diodes and a photodiode which are installed on an extension, a control panel with an audio indication unit, a timer, an autonomous laser-triggering generator, a laser power-supply and protection unit, a light-emitting diode power-supply unit, and a reflected emission indicator with a synchronizer with includes cardiac-rhythm signal detectors. The cardiac- rhythm signal detectors' input is a signal received from a biological object and output is connected to a cardiac-rhythm signal amplifier, one of whose outputs is connected to a display, while the other output is connected to an input of R-wave selector which is connected to a pulse-bunch former. The first output of the pulse-bunch former is also connected to the display. The pulse bunches formed are supplied with the required delay to a power-supply and protection unit as its second output. The pulse-bunch former is connected to an autonomous laser-triggering generator and is capable of being triggered both externally and internally.

Russian patent 1806781 to Leveshunov et al., deals with magnetic-laser treatment to improve clinical prognosis, and reduce treatment duration, of patients with complicated acute myocardial infarction. Pulsed laser irradiation and infrared radiation (wavelength not mentioned) are applied to the patients' chest wall.

Russian patent 1806781 states that "the essence of the method is the daily simultaneous application of a magnetic field with induction of 40 mT, pulsed laser radiation with a power of 4W and a repetition rate of 4.5-5 Hz, and a continuous infrared radiation with a power of 50 mW to the precordial region with an exposure time equal to 5 min. for an 8-10 day period". There is no data known to the art on the bioeffects of combination of magnetic field and laser irradiation on tissues. The pulsed laser, as suggested in this patent, has a mean power of 12 mW, while the continuous infrared radiation has a power of 50 mW.

However, the laser beam has to penetrate through the chest skin and muscles between the ribs with a total average tissue width of about 1 cm before reaching the heart muscle. Since the laser power diminishes within living tissue in an exponential manner with respect to depth, the maximal laser power output, as suggested by Leveshunov et al., will be reduced through the thick chest wall of a patient to practically less than a few mW, i.e., less than the minimal energy to cause any stimulatory effect on the heart muscle. Indeed, the authors themselves claim on the first page of their patent that "the positive effect of the invention is a reduction in the treatment period... " after acute myocardial infarction.

Neither Russian patent 2022574 to Aleshin et al. nor Russian patent 1806781 to Leveshunov et al. describe or suggest apparatus for biostimulation by electromagnetic wave radiation of myocardioal tissue by irradiation with an optical fiber that is introduced by a catheter into a ventricle. 7A SUMMARY OF THE INVENTION The present invention seeks to provide apparatus for improvement of heart function and eliminating scar tissue formation and for regeneration of myocardial tissue following myocardial infarction, or other heart failure syndromes, by electromagnetic wave radiation. The apparatus includes an electromagnetic wave radiation transducer which communicates with a source of electromagnetic wave radiation via at least one optical fiber, the electromagnetic wave radiation transducer being operative to irradiate an infarct of a myocardium after insertion of said at least one optical fiber through a catheter into a ventricle, an echo transducer which communicates with an echo imaging device, the echo transducer being operative to provide positional information of the infarct, and a fastener which fastens the electromagnetic wave radiation transducer together with the echo transducer and which substantially maintains the transducers in a fixed spatial relationship with each other.

The apparatus is not limited to use at any particular range of wavelengths, however, the best mode of carrying out the invention is in the range including infrared, visible light and ultraviolet radiation. The choice of which particular wavelength, power level, duration of irradiation and number of irradiation sessions is made in accordance with the patient's needs.

The radiation may be coherent, such as radiation provided by a laser or may alternatively be non-coherent, such as provided by a xenon light bulb. The method may be non-invasive both to the body and to the heart, such as by placing a radiation transducer on the outer skin of the patient and irradiating the myocardium therefrom.

Alternatively, some body tissue, such as non-myocardial muscle tissue, may be at least partially exposed, such as 8 on the chest or back of the patient, and the transducer used to irradiate the heart therefrom. Although this option is partially invasive to the body, it has the advantage of allowing the irradiation to penetrate through a thinner muscle layer and attaining a higher and optimal irradiative power on the heart 8A muscle. Still alternatively, the method may be invasive to the heart, such as by irradiating the heart with an optic fiber introduced by a catheter, such as into a coronary artery or through the aortic valve into the internal volume of the ventricle.

Some examples of biostimulation of the myocardium are a reduction in the size of the infarct, regeneration of cardiomyocytes in the infarct, preservation of the structure and activity of mitochondria in cardiomyocytes, and improved function of diseased myocardium. It is a particular feature of the present invention to use light to cause regeneration of cardiomyocytes. Heretofore, the art does not know of any method for regeneration of cardial muscle.

There is thus provide in accordance with a preferred embodiment of the present invention, a method for biostimulation of a myocardial tissue including the step of irradiating the myocardial tissue with a source of electromagnetic wave radiation which causes biostimulation of the myocardial tissue. Preferably the electromagnetic wave radiation is selected from the group consisting of infrared, visible light and ultraviolet radiation.

In accordance with a preferred embodiment of the present invention, the step of irradiating is performed after the myocardial tissue develops an infarct, the infarct being characterized by a size, and the irradiating of the myocardial tissue causes a reduction in the size of the infarct.

Additionally in accordance with a preferred embodiment of the present invention, the step of irradiating is performed after the myocardial tissue develops an infarct, and the 9 irradiating of the myocardial tissue causes regeneration of cardiomyocytes in the infarct.

Further in accordance with a preferred embodiment of the present invention, the step of irradiating is performed after the myocardial tissue develops an infarct, and the irradiating of the myocardial tissue preserves structure and activity of mitochondria in cardiomyocytes in the infarct.

In accordance with a preferred embodiment of the present invention, the source of electromagnetic wave radiation includes a source of coherent light. The source of coherent light may include a diode laser. In accordance with a preferred embodiment of the present invention, the diode laser has a power output in the range of 30 - 500 mW and a wavelength in the range of 250 - 940 nm.

Further in accordance with a preferred embodiment of the present invention, the step of irradiating includes a plurality of irradiations of the myocardial tissue with the source of electromagnetic wave radiation.

In accordance with a preferred embodiment of the present invention, the step of irradiating includes irradiating the myocardial tissue with the source of electromagnetic wave radiation for a duration of 0.5 - 15 minutes.

Alternatively in accordance with another preferred embodiment of the present invention, the method further includes the step of at least partially exposing non-myocardial tissues in a generally perpendicular direction to a lateral wall of the myocardial tissue, and wherein the step of irradiating includes 10 placing the source of electromagnetic wave radiation onto the at least partially exposed non-myocardial tissues.

In accordance with yet another preferred embodiment of the present invention, the myocardial tissue is located in a ventricle and the step of irradiating includes irradiating the myocardial tissue with at least one optical fiber introduced by a catheter into the ventricle or chest cavity. The at least one optical fiber may be introduced through an aortic valve or into a coronary artery. Additionally, an optic fiber may be introduced into the ventricle or chest cavity for observing the irradiation.

In accordance with another preferred embodiment of the present invention, the source of electromagnetic wave radiation includes a source of concentrated non-coherent light. The source of concentrated non-coherent light may include a xenon light bulb. Preferably the xenon light bulb has an irradiative power 2 flux of 100 - 500 mW/cm .

There is also provided in accordance with a preferred embodiment of the present invention, apparatus for biostimulation by electromagnetic wave radiation of a myocardial tissue including an electromagnetic wave radiation transducer which communicates with a source of electromagnetic wave radiation, the electromagnetic wave radiation transducer irradiating an infarct of a myocardium, an echo transducer which communicates with an echo imaging device, the echo transducer being operative to provide positional information of the infarct, and a fastener which fastens the electromagnetic wave radiation transducer together with the echo transducer and which substantially maintains the transducers in a fixed spatial relationship with each other.

BRIEF DESCRIPTION OF THE DRAWINGS The present invention will be understood and appreciated more fully from the following detailed description, taken in conjunction with the drawings in which: Fig. 1 is a simplified flow chart of a method for biostimulation of a myocardial tissue in accordance with a preferred embodiment of the present invention; and Fig. 2 is a simplified pictorial illustration of apparatus for biostimulation of myocardial tissue by electromagnetic wave radiation, constructed and operative in accordance with a preferred embodiment of the present invention. 12 DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Reference is now made to Fig. 1 which illustrates a simplified flow chart of a method for biostimulation of a myocardial tissue in accordance with a preferred embodiment of the present invention. The method includes irradiating the myocardial tissue with a source of electromagnetic wave radiation which causes biostimulation of the myocardial tissue. The method is not limited to any particular range of wavelengths, however, the best mode of carrying out the invention is in the range including infrared, visible light and ultraviolet radiation. The choice of which particular wavelength, power level, duration of irradiation and number of irradiation sessions is made in accordance with the patient's needs.

As will be described hereinbelow with reference to experimental results, the radiation may be coherent, such as radiation provided by a laser or may alternatively be noncoherent, such as provided by a xenon light bulb. The method may be non-invasive both to the body and to the heart, such as by placing a radiation transducer on the outer skin of the patient and irradiating the myocardium therefrom. Alternatively, some body tissue, such as non-myocardial muscle tissue, may be at least partially exposed, such as on the chest or back of the patient, and the transducer used to irradiate the heart therefrom. Although this option is partially invasive to the body, it has the advantage of allowing the irradiation to penetrate through a thinner muscle layer and attaining a higher and optimal irradiative power on the heart muscle. Still 13 alternatively, the method may be invasive to the heart, such as by irradiating the heart with an optic fiber introduced by a catheter, such as into a coronary artery or through the aortic valve into the internal volume of the ventricle. Alternatively, the method may be invasive to the chest cavity, such as by introducing an optic fiber into the chest cavity and irradiating the heart muscle directly from the chest cavity.

The irradiation causes biostimulation of the myocardium, as will be described in further detail below. For example, by irradiating the myocardial tissue after the development of an infarct, the irradiation may cause a reduction in the size of the infarct, may cause regeneration of cardiomyocytes in the infarct, may preserve structure and activity of mitochondria in cardiomyocytes in the infarct and prevent their rapid degeneration after onset of myocardial infarct or ischemia, and/or may improve function of diseased myocardium.

Several experiments, were carried out in accordance with alternative preferred embodiments of the present invention and the results of these experiments are now summarized.

Experiment I Forty-nine male Sprague-Dawley ether-anesthetized rats, 6-8 weeks old (220-260 g body weight) were used for the experiments. Two-cm incisions to the left of and parallel to the sternum were made; the fifth and sixth ribs were separated with a clamp, and the hearts were exteriorized by applying pressure to the lateral aspects of the thoracic cage. The left coronary 14 arteries were then occluded 2-3 nun from their origins with single sutures. The chests were closed and the rats allowed to recover. This procedure induces a "heart attack" or ischemic heart in these rats.

Twenty-three rats were irradiated immediately following surgery using a diode laser (wavelength 780nm; 38 mW). The irradiation was performed by placing and gently pressing a laser source tip onto the exposed intercostal muscles approximately in a perpendicular direction to the lateral wall of the left ventricle. The laser source was moved in a constant velocity for 2 min to cover the chest area from the sternum laterally to the left and between the 4th and the 8th rib in a medial-lateral direction.

In a separate experiment the efficiency of the laser penetration through the intercostal muscles of the rat (about 2 mm thick) was determined by placing the laser source as above and measuring the laser power with a special laser meter inserted in the chest cavity underneath the laser source. The laser power was at least 6 mW which is approximately the power that reaches the heart muscle.

Laser irradiation was repeated in the same way on the 3rd day post-operatively but for 3 min under light ether anesthesia. Control rats were sham operated as the above-treated (laser irradiated) rats but were not exposed to laser irradiation. All the rats were ether-anesthetized at 21 days post-operatively, the chest opened and the heart (while beating) excised and immediately washed to remove blood by soaking in ice-cold saline for about 5 sec. The heart was then transversely cut 15 into three equal parts (about 2 mm) from its apex. The middle section was fixed in neutral buffered formalin for 24 hr. The sections were dehydrated in alcohol embedded in paraffin and stained in Masson's trichrome.

The infarcted zone in each heart (the area where connective scar tissue was formed instead of contracting muscular tissue) was traced by differential staining of the scar tissue in Masson's staining. The infarct size was calculated in each section as a percentage occupied by scar connective tissue out of the total area of the left ventricle. Quantitative morphometric measurement and statistics were performed as described previously in N. Weiss and U. Oron, ibid, and 0. Barushka, T. Yaakobi and U. Oron, ibid.

The infarct size in the control rats was 29.6 + 4.3%; in the laser irradiated rats it comprised only 9.5 + 0.9%, significantly (P<0.001) lower than the infarct size in the control rats.

Possible adverse effects of the laser were investigated by irradiation of sham operated (heart exteriorized from the chest without coronary occlusion) rats compared to sham non-irradiated rats. The enzymatic activity of creatine phosphokinase (marker for cell viability) in the myocardium of both irradiated and non-irradiated rats was the same. No ultrastructural changes were observed in the myocardium of the irradiated rats as compared to control non-irradiated ones.

From the results of Experiment I, it is seen that laser irradiation after heart infarction causes about a 70% reduction 16 of infarct size as compared to control non-irradiated rats. The mode of action of the low energy laser on cells in general and cardiomyocytes in particular is not yet clearly understood. The marked reduction of infarct size by low energy lasers and light may be of prime clinical importance. It may reduce the mortality in acute myocardial infarction in humans, especially in young people. It may also reduce the need for by-pass heart surgery following acute MI. It could also help to preserve the muscular tissue in hibernating (cooled) hearts separated from the blood circulation during open-heart or bypass surgery. Furthermore, it may improve the function of the heart muscle in various heart diseases (angina pectoris, for example).

Experiment II Heart infarction was induced in 22 rats as described in Experiment I. Ten rats served as control and 12 rats underwent a different laser irradiation than in Experiment I. The laser used was a diode laser with energy of 47 mW and wavelength of 830 nm and irradiation was performed as described in Experiment I, but for 5 min immediately following induction of infarction. On the third and fourth day, post-infarction the rats underwent a further two sessions of laser irradiation under the same conditions as above. The rats were sacrificed after 21 days and the infarct size calculated as in Experiment I. The infarct size of control rats was 31 + 7%, whereas in the laser irradiated rats it comprised only 5.5 + 1.2% [significantly (p < 0.001) lower than control] . The infarct size of the laser irradiated rats was also significantly smaller (p < 0.05) than that of the laser irradiated rats in Experiment I. 17 From the results of Experiment II, it is seen that in various wavelengths (at least in the range of 700-830 nm), output power, time of irradiation (which determines the total energy-given to the tissue) and timing after infarct induction of the beneficial effect of the laser irradiation on the infarcted heart is relevant. Moreover, the induction of the infarct size was even better in Experiment II than in Experiment I.

An additional experiment with substantially the same procedure as Experiment II was carried out using a laser power level of 250 mW, with similar results.

Experiment III Heart attacks were induced to another group of 21 rats as described in Experiment I. Ten rats served as control and 11 rats underwent the laser treatment as described in Experiment I . After 21 days post induction of heart attack, the hearts were removed and connected to a Langendorff apparatus in an artificial physiological solution. They were then injected with TTC ( triphenyltetrazolium chloride) through the coronary arteries. This solution stains "healthy" uninjured heart cells with red and injured scar tissue in the heart with a pale yellow color. The hearts were then fixed in neutral buffered formalin and sectioned transversely. Quantitative morphometric measurements and statistics were performed as in Experiment I .

The infarct size (injured pale yellow area as percent of total area of the left ventricle) was 32+5% in the control group which was significantly (P < 0.01) higher than laser irradiated group which comprised 8+3%. 18 Experiment IV Heart infarction was experimentally induced in 24 rats as described in Experiment I . Twelve rats were laser irradiated as in Experiment I and 12 rats served as control. At 6 and 21 days post-experimentally induced infarct, 6 control and 6 laser irradiated rats were sacrificed and histological sections from the heart were prepared as in Experiment I . The sections were stained with antibody to desmin in order to trace cells which synthesize newly-formed myogenic contractile proteins. As is known in the art, desmin is a protein which serves as a marker for embryonic muscle cells. Desmin is only found in the cytoplasm of cells that synthesize myogenic contractile proteins. It was found that many cells in the infarct zone in the laser irradiated rats were positively . stained to desmin whereas in the non-irradiated rats there was almost no staining for desmin.

It is seen from Experiment IV, that laser irradiation may be used to induce formation of new regenerative heart cells in the infarcted area. This embodiment of the present invention is an important medical discovery and is a radical departure from current art which does not know how to induce regeneration of cardiomyocytes .

Experiment V The same experimental system was used as in Experiment I ( induction of MI in rats ) . Twenty rats underwent the procedure for creating MI in the myocardium of the left ventricle. Ten rats served as control sham operated rats, while another ten rats were irradiated immediately following surgery with concentrated light produced b a xenon light bulb. The output energy of the light 2 source was about 250 mw/cm . The light beam ( about 2 cm in diameter) was aimed directly at the intercostal exposed and partially cut chest muscles (in order to allow better penetration of light to the chest cavity and heart) above the location of the heart for 10 min. Light irradiation was repeated as above also during the second and fourth days post infarction, once a day. At 21 days post operatively, the hearts of both control and light irradiated rats were exposed and treated for measurement of infarct size as in Experiment I. The infarct size was 32 + 6% in the control rats compared with 22 + 4% in the light irradiated rats. There was a 30% significant (P < 0.05) reduction in infarct size in the light irradiation rats.

It is seen from Experiment V, that not only coherent laser irradiation but also concentrated light can cause a significant reduction in infarct size.

Apparatus for biostimulation by electromagnetic wave radiation of myocardial tissue will now be described.

Reference is now made to Fig. 2 which illustrates apparatus 10 for biostimulation by electromagnetic wave radiation of a myocardial tissue. Apparatus 10 preferably includes an electromagnetic wave radiation transducer 12 which communicates with a source 14 of electromagnetic wave radiation, such as a diode laser. Radiation transducer 12 transmits radiation from source 14 onto an infarct 16 of a myocardial tissue 18.

Apparatus 10 also preferably includes an echo transducer 20 which communicates with an echo imaging device 22. Echo transducer 20 provides positional information of infarct 16. 20 A fastener 24 fastens radiation transducer 12 together with echo transducer 20 and substantially maintains transducers 12 and 20 in a fixed spatial relationship with each other . Fastener 24 may be any type of band, clamp, housing or bracket, for example, and may be made of any suitably stiff material such as metal or plastic. Echo transducer 20 may be used to monitor the position and size of infarct 16 while simultaneously irradiating infarct 16 with radiation transducer 12.

An example of source 14 is now described. Source 14 may include a laser unit powered by a power supply which is preferably capable of emitting 3-6 volts. This laser unit preferably includes a multiplicity of diode lasers, pulsed or continuous, with a preferable wavelength in the range of 630-940 nm and a total modulated power output of 40 - 500 mW. Alternatively, source 14 may include a source of xenon or ultraviolet light, for example.

The diode lasers may be spaced 0.5 - 1 cm from each other and mounted on a base. The base is preferably arcuate in shape and may be constructed of a suitably sturdy material, such as plastic, plexiglass or steel. Typically, the base may be 5 50 cm in length and 20 cm wide, with 60-100 diode lasers mounted thereon. The laser unit is preferably provided with a computer controlled on/off switch.

The laser unit may be further provided with an automatic scanning controlled lever arm. The lever arm is preferably mounted on an adjustable telescopic electric support having "all-direction" wheels. A control system may be provided which, inter alia, may control duration and power level of 21 irradiation, automatically switch-off the irradiation at the end of treatment, display operational information and allow adjustment of operational parameters during treatment.

Another example of radiation source 14 is a laser unit comprising a plurality of preferably portable, versatile (continuous or pulsed) diode lasers or any other (e.g., He-Ne) laser sources at modulated wavelengths, 639-940 run, with a modulated power output of 40-500 mW, and a modulated beam diameter. In this example, radiation transducer 12 preferably comprises an optical fiber of various diameters (0.3-5.0 mm) and lengths, connected to the laser source. At a distal end of the optical fiber is preferably mounted a non-imaging conical light ejecting tip. The optical fiber may be inserted by a catheter into a blood vessel of a patient during angiography, and conveyed into the coronary artery or ventricle to reach the non-contracting ( infarcted ) zone in the heart muscle ( not shown ) . The infarcted zone and the location of light ejecting tip may be identified simultaneously on a computer screen by conventional devices and/or echo imaging units used during conventional angiography .

It will be appreciated by persons skilled in the art that the present invention is not limited by what has been particularly shown and described hereinabove. Rather the scope of the present invention is defined only by the claims which follow: 22

Claims (2)

118968/4 What is claimed is:

1. Apparatus for biostimulation by electromagnetic wave radiation of a myocardial tissue comprising: an electromagnetic wave radiation transducer which communicates with a source of electromagnetic wave radiation via at least one optical fiber, said electromagnetic wave radiation transducer being operative to irradiate an infarct of a myocardium after insertion of said at least one optical fiber through a catheter into a ventricle, an echo transducer which communicates with an echo imaging device, said echo transducer being operative to provide positional information of said infarct, and a fastener which fastens said electromagnetic wave radiation transducer together with said echo transducer and which substantially maintains said transducers in a fixed spatial relationship with each other.

2. Apparatus substantially as shown and described hereinabove . For the Applicant, Sanford T. Colb & Co. C: 25075 23