Erectile Dysfunction Shock Waves Therapy (EDSWT)

Transcription

1 1 Updated: Mar Erectile Dysfunction Shock Waves Therapy (EDSWT)

2 2 Man survives earthquakes, experiences the horrors of illness, and all of the tortures of the soul. But the most tormenting tragedy of all time is, and will be, the tragedy of the bedroom. Tolstoy

3 3 Agenda EDSWT: From Physics to Physiology EDSWT: Mechanism of action in-vitro/in-vivo models ED1000 system Treatment procedure Treatment strategy Current and future indications

4 4 Shock wave technology From Physics to Physiology

5 5 Shock Wave Therapy Applications Shock Wave Pressure Level (Bar) ~900 Bar Stone Fragmentation Urology ~400 Bar Anti inflammatory ~100 Bar Orthopedics Angiogenesis ~100 Bar Angiogenesis Energy Density Level (mj/mm²) 100 Cardiology Vascular (ED) s 90 s Clinical Field

6 6 Shock waves in medical fields Urology Lithotripsy of urinary calculosis Microbiology Reduction of bacterial growth Gastyroenterology Disintegration of calcium deposits in the pancreas Shock waves Dentistry Regeneration of bone loss in periodontal disease Antibacterial effect associated with oral infections Disintegration of calcium deposits in obstructive sialadenitis Wound medicine Treatment of chronic soft tissue wounds Andrology Treatment of organic erectile dysfunction Oncology Acceleration of drug delivery to targets in the human body Traumatology and orthopedics Treatment of osteochondral lesions Treatment of femoral head necrosis Treatment of chronic plantar fasciitis Decalcification of calcific tendonitis Treatment of Morton's neuroma

7 7 Shockwave sources Lightning & thunder Supersonic airplane Gun shot

8 8 Shock waves characteristics Oscilloscope image Positive peak pressure Steep rise Short time duration Low tensile wave component V=1500m/sec in water

9 9 Shock wave effect Shock wave Mechanical response Biochemical response Clinical response Increase in regional perfusion

10 10 Shear-stress effect on cell membrane Positive pressure wave Tensile wave 2 Shear Stress 1. Positive pressure - Compression forces 1 2. Negative / Tensile pressure - Expansion forces 3. Shear stress - biomechanical force generated on the surface of the endothelium. Cell Membrane

11 11 Shear stress effect Shear stress effect enos activation NO production relaxation of smooth muscles Galley & Webster 2004

12 12 Cavitation effect 1. Shock wave creates mechanical pressure and tension force on the tissue. 2. Behind the pressure front, there s a cavitation effect: formation and collapse of bubbles that produces micro jet of the secondary energy. 3. Physical forces generated by cavitation are highly localized.

13 13 Formation of cavitations Maximally expanded bubble Internal collapse Jet of kinetic force Journal of Mineralstoffwechsel 2004

14 14 Angiogenesis: Background Angiogenesis formation of thin-walled endothelium-lined structures with muscular smooth muscle wall. Angiogenic regulatory factors: vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF), angiopoietins (Ang), platelet-derived growth factor, angiogenin, angiotropin, hepatocyte growth factor, platelet endothelial cell adhesion molecule, and others. Angiostatic factors: angiostatin, endostatin, thrombospondin, CXC chemokines, and pigment epithelium derived factor. Homeostatic conditions: a balance between these pro- and antiangiogenic factors. Injury: the balance shifts toward pro-angiogenic factors to drive repair.

15 15 Main angiogenesis markers Endothelial nitric oxide synthase (enos) an enzyme that catalyze production of nitric oxide (NO) in blood vessels and involved in regulating vascular function. Vascular endothelial growth factor (VEGF) - family of a growth factors involved in both vasculogenesis (formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). Endothelial Progenitor Cells - population of the cells with ability to differentiate into endothelial cells, the cells that make up lining of blood vessels.

16 16 Biochemical response VEGF The and precise flt-1 mechanism upregulation of SW - to SW induce upregulates angiogenesis VEGF remains and its to be receptor, fully elucidated. Flt-1, in SW is a longitudinal acoustic wave, traveling with the speed in water of ultrasound through body endothelial tissue, and cells could in be vitro focused and on VEGF an area in the of several ischemic millimeters myocardium in diameter in vivo. [12]. SW is known Endothelial to exert the Progenitor cavitation Cells effect recruitment (a micrometer-sized - SW recruits violent collapse systemically of bubbles infused inside and outside the cells) [12] and recently has been demonstrated to induce localized stress on cell Endothelial membranes Progenitor that resembles Cells shear in a rat stress model [13]. of chronic limb ischemia NO synthesis SW has also - been SW causes demonstrated nonenzymatic to cause nonenzymatic nitric oxide nitric synthesis oxide synthesis from L -arginine from L-arginine and and hydrogen peroxide [14], which may be involved, at least in part, in the biochemical hydrogen effects peroxide of SW. Anti-inflammatory Furthermore, recent effect- orthopedic Modulation studies have of neuronal demonstrated NOS that catalytic SW therapy activity, induces NO production, neovascularization at tendon [7,15], via upregulation of endothelial nitric oxide synthesis, VEGF, and NFkapaB proliferating activation, cell antigen isoform [15]. NOS and TNF-alpha mrna expression Vasodilation We have previously SW reduces confirmed arterial that SW perfusion upregulates pressure VEGF and in its artificially receptor, Flt-1, perfused in rabbit kidneys endothelial with immediate cells in vitro increase and VEGF in the blood ischemic flow myocardium around the in treated vivo [9]. area As the VEGF Flt system is essential in initiating vasculogenesis and/or angiogenesis, this Neovascularization effect of SW could explain, SW induces at least in neovascularization part, the underlying mechanisms at tendon via for SW-induced upregulation of endothelial angiogenesis. nitric oxide synthesis, VEGF, and proliferating cell antigen. In this study, myocardial perfusion in the ischemic myocardium was improved only where Local the perfusion SW was applied - Myocardial (Fig. 3), excluding perfusion the in placebo the ischemic effect of the myocardium therapy. was improved only where the SW s were applied.

17 17 Shockwaves pre-clinical studies In-vitro/In-vivo

18 18 Physiological Effects Physiological Effect Based on Study Source Shear stress Shockwave exert a cavitation effect (inside and outside of cells) inducing localized stress on cell membranes that resembles shear stress Maisonhaute E, Prado C, White PC. Surface acoustic cavitation understood via nanosecond electrochemistry. Ultrason Sonochem 2002; NO synthesis Shockwave cause nonenzymatic nitric oxide synthesis from L - arginine and hydrogen peroxide. Gotte G, Amelio E, Russo S. Short-time non-enzymatic nitric oxide synthesis from L-arginine and hydrogen peroxide induced by shock waves treatment. FEBS Lett VEGF and flt-1 upregulation Endothelial Progenitor Cells recruitment SW upregulates VEGF and its receptor, Flt-1, in endothelial cells in vitro and VEGF in the ischemic myocardium in vivo. Shock Wave Therapy recruits systemically infused Endothelial Progenitor Cells on a rat model of chronic limb ischemia. Nishida T, Shimokawa H, Oi K, Tatewaki H. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia -induced myocardial dysfunction in pigs in vivo. Circulation 2004 Aicher A, Heeschen C, Sasaki K. Low-Energy Shock Wave for Enhancing Recruitment of Endothelial Progenitor Cells - A New Modality to Increase Efficacy of Cell Therapy in Chronic Hind Limb Ischemia. Circulation Anti-inflammatory Modulation of neuronal NOS catalytic activity, NO production, NF-кB activation, isoform NOS and TNF-alpha mrna expression Ciampaa AR, Marlinghause E, Suzukia H. Nitric oxide mediates antiinflammatory action of extracorporeal shock waves. FEBS Lette 2005 Neovascularization SW therapy induces neovascularization at tendon via upregulation of endothelial nitric oxide synthesis, VEGF, and proliferating cell antigen. Wang CJ, Wang FS, Yang KD. Shock wave therapy induces neovascularization at the tendon-bone junction. A study in rabbits. J Orthop Res 2003 Local perfusion increased Vasodilatation Myocardial perfusion in the ischemic myocardium was improved only where the SW s were applied. Shockwaves acutely reduces arterial perfusion pressure on artificially perfused rabbit Fukumoto Y, Shimokawa H et al 2006 Seemann O, Rassweiler J, Chvapil M. The effect of single shock waves on the vascular system of artificially perfused rabbit kidneys. J Stone Dis. 1993

19 Ciampaa AR et al. Nitric oxide mediates anti-inflammatory action of extracorporeal shock waves Stimulation of NO synthase activity Extracorporeal shockwaves at a low energy density increase nitric oxide synthase (NOs) activity and nitric oxide (NO) production in the rat glioma cells. NOs is a shockwave dose - dependent Maximum level of enos activation at an energy level of 0.03 to 0.11

20 20 Recruitment of EPC Adductor muscles of hind limb of nude rat: ischemic limb (treated with SW s), non-ischemic limb (treated with SW), control limb (no ischemia, no SW) Preconditioning with low-energy SW followed by injection of EPC Recruitment of circulating EPCs to ischemic and nonischemic tissue Control Non-ischemic tissue Ischemic tissue (HLI - Hind Limb Ischemia:>1000 impulses) Aicher A. et al. Low-Energy Shock Wave for Enhancing Recruitment of Endothelial Progenitor Cells. Circulation 2006

21 21 Recruitment of EPC (2) Effect of SW treatment on the number of VEGF cells (chemoattractant factor for EPC) in ischemic and non-ischemic tissue Control Non-ischemic tissue Hind Limb Ischemia:>1000 impulses) Aicher A. et al. Low-Energy Shock Wave for Enhancing Recruitment of Endothelial Progenitor Cells. Circulation 2006

22 22 Shock wave induces neovascularization Rabbits: right limb (study side) treated with SW and the left limb (control side) no SW. Neovascularization confirmed by biopsy and angiogenic markers (VEGF, enos). Angiogenic markers following SW s returns to baseline values after 12 wks. Wang CJ. Shock wave therapy induces neovascularization at the tendon-bone junction. A study in rabbits.. J Orthop Res 2003

23 23 Shockwaves induces neovascularization (2) Dogs: right limb (study side) treated with low-energy SW; left limb (control side) did not receive SW. Neovascularization confirmed by microscopic examination. Specimens: new capillary and muscularized vessels. Myofibroblasts: study specimens - predominantly at 8 weeks; control specimens: myofibroblasts were not seen. Wang CJ Shock wave-enhanced neovascularization at the tendon-bone junction: an experiment in dogs. J Foot Ankle Surg. 2002

24 24 Shockwave effect on ischemia Rabbits: surgically excised unilateral femoral artery treated with shock wave therapy (Tx group) and not treated (control group) Low energy: 0.09 mj/ mm 2, Surgical Procedure Shock Wave Tx: 0.09 mj/ mm 2, 30 spots, 200 shots/spot Collateral arteries development, flow ratio, blood pressure ratio, capillary density 1 week 1 week 1 week Tx group 1 week 2 week 3 week 4 week 3 weeks ntrol group 1 week 2 week 3 week 4 week 3 weeks Oi K et al. Extracorporeal shock wave therapy ameliorates hind limb ischemia in rabbits. Tohoku J Exp Med. 2008

25 25 Shock wave effect on ischemia (2) Collateral development post shock wave treatment (iliac angiography) Oi K et al. Extracorporeal shock wave therapy ameliorates hind limb ischemia in rabbits. Tohoku J Exp Med. 2008

26 26 Shock wave effect on ischemia (3) Capillary density post shock waves (day 28) Control group Tx group Oi K et al. Extracorporeal shock wave therapy ameliorates hind limb ischemia in rabbits. Tohoku J Exp Med * Capillary / Muscle Fiber ratio

27 27 Shock wave effect on ischemia-induced myocardial dysfunction Pigs: Ameroid constrictor put around LCx to gradually (4 weeks) - artery occlusion without causing myocardial infarction. In 4 weeks SW group received shock wave therapy (SW group) and control group did not. Ameroid Constrictor (AC) Shock Wave Treatment (0.09 mj / mm 2, 9 spots, 200 shots/spot) 1 week 4 weeks 4 weeks Echocardiography, myocardial blood flow Echocardiography, myocardial blood flow, CAG, LVG Echocardiography, myocardial blood flow, CAG, LVG Nishida. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation 2004

28 28 Shock wave effect on ischemia-induced myocardial dysfunction (2) Enhancement of Coronary Collaterals Control group SW group 4 weeks post AC implantation 4 weeks post SW treatment Nishida T Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs Circulation 2004

29 29 Shock wave effect on ischemia-induced myocardial dysfunction (3) Left ventricle wall motion (ventriculography) : improvement of myocardial function Control group SW group 4 weeks post AC implantation 4 weeks post SW treatment Nishida T Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs Circulation 2004

30 Nishida. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation Shock wave effect on ischemia-induced myocardial dysfunction (4) Improvement in LV Ejection Fraction 70 SW (n=8) Control (n=8) 60 P< 0.01 LVEF (%) Pre treatment Post treatment

31 31 Shock wave effect on ischemia-induced myocardial dysfunction (5) Nishida. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation 2004 Endocardium Improvement of Regional Myocardial Blood Flow (colored microspheres) RMBF (ml/min/g) 3 SW (n=8) 2 Control (n=8) 1 P< Baseline 4 weeks 8 weeks Epicardium RMBF (ml/min/g) P<0.05 SW (n=8) Control (n=8) 0 Baseline 4 weeks 8 weeks

32 32 Shock wave effect on left ventricular remodeling after reperfusion injury (2) Shock wave therapy improved LVEDV, LVEDP and LVEF LVEDV - 4 weeks post R/I LVEF - 4 weeks post R/I LVEDP - 4 weeks post R/I [ml] [%] [mmhg] P< Control SW 0 Control SW 0 Control SW Ito Y et al. Cardiac shock wave therapy ameliorates left ventricular remodeling after myocardial ischemia-reperfusion injury in pigs in vivo. Coron Artery Dis. 2010

33 Extracorporeal Shock Wave Therapy Reverses Ischemia-Related Left Ventricular Dysfunction and Remodeling: Molecular-Cellular and Functional Assessment Morgan Fu.et al. Plos ONE Shock Wave Reverses Ischemia-Related LV Dysfunction and Remodeling Study design

34 34 Shock Wave Reverses Ischemia-Related LV Dysfunction and Remodeling (2) Number of small vessels Number of apoptotic nuclei Normal Ischemia Ischemia + SW Fibrotic area Normal Ischemia Ischemia + SW

35 35 Shock Wave Reverses Ischemia-Related LV Dysfunction and Remodeling (3) Ischemic heart + Shockwave Enhanced Angiogenesis Promoted EPC Homing Suppressed Apoptosis Preserved Mitochondrial Function Reduced Oxidative Stress Alleviated Inflammation Increased endothelial cells in ischemic tissue Attenuated cardiomyocyte death Attenuated myocardial fibrosis Attenuated inflammation response Limited Remodeling & Preserved Cardiac Function Mean fibrotic area Cx43 protein expression LVESV LVESD LVEDP LVEF FS

36 36 Shock wave physiological response on ischemia (1) Summary SW s induces local angiogenesis The effect is dose dependant The effect is energy dependant The effect is local and focused Angiogenesis factors released into the blood following SW s have a limited life span

37 37 Shock wave physiological response on ischemia (2) Summary SW s improve myocardial ischemia SW s reduce the remodeling effect following myocardial ischemia SW s reduce the impact of ischemiareperfusion injury SW s reverses ischemia-related left ventricle dysfunction

38 38 Low-energy shockwave effect Shock wave Shear stress Mechanical response Cavitation Biochemical response Endothelial Nitric Oxide Synthaze (enos) Vascular Endothelial Growth Factor (VEGF) Endothelial Progenitor Cells (EPC) Short-term response Clinical response Long-term response Vasodilatation Angiogenesis Increase in local perfusion Neovascularization

39 39 BREAK

40 40 Shock wave technologies Electrohydraulic / Ellipsoid Spark Gap technology: uses a spark plug to generate a shockwaves focused by an ellipsoid reflector. Electromagnetic / Flat Coil (Lens) Uses a cylindrical coil arrangement of an electromagnetic generator and a parabolic reflector to focus the shockwaves. Piezoelectric / Sphere Ceramic elements are lined on a reflector dish with shock waves generated by an electric pulse. Shock waves focused by thousands of small crystals in the applicator head.

41 41 Ellipsoid Advantages Each shock wave travels the same distance from F1 to F2, and reaches F2 at the same time F1 F2 Semi ellipsoid of the Cardiospec Shock Wave Applicator F1 (Electrode) F2 (Focal zone)

42 42 Shock waves - principles Generated by electro-hydraulic effect: High voltage creates electric spark discharge The water vaporizes and creates an explosion Generating high energy Shock Waves Reflected by the Semi-Ellipsoid Focused onto the treatment area

43 43 Shock wave therapeutic coverage MPa Max Pressure Therapeutic effect Therapeutic Zone Depth of Therapeutic Zone (Transmural effect) 5 MPa No therapeutic effect mm Area of therapeutic zone (Area of therapeutic effect) Wess O et.al. Working Group Technical Developments - Consensus Report. High Energy Shock Wave in Medicine. 1998

44 44 Shock wave frequency (Fourier Transform) Pulse Wave Length: 4 μs Pick Frequency: 300KHz (100KHz - 1 MHz) Cleveland, McAteer 2004

45 45 Shock waves vs. ultrasound waves Mechanical Pressure (shear stress) High Energy (100 Mpa) Not reflected by ribs (larger acoustic window) Focused waves Pressure P < 0.5 MPa Time Heating effect (protein denaturation) Low Energy (<0.5 Mpa) Reflected by ribs (limited acoustic window) Diffused wave

46 46 Attenuation of SW s in tissue Material Density (kg/m 3 ) Velocity of sound (m/s) Acoustic Impedance ( kg / m 2 s) Air Water x 10 6 Fat x 10 6 Muscle x 10 6 Bone: Cortical x 10 6 Cancellous ~ x 10 6 Body tissues has low attenuation effect

47 47 Extracorporeal Shockwave Myocardial Revascularization Cardiospec system

48 48 ESMR principle Skin level Shockwave applicator Focal Zone Low-energy, focused shock waves Energy density: 0.09 mj/mm 2 Echo-guided treatment ECG-gated (R-wave)

49 49 System components Control Panel Ultrasound probe holder Shock Wave Applicator ECG monitor Treatment table Power Cabinet

50 50 System components Positioning device (X- and Y- axis movement) Shock wave applicator with inflated membrane Echo transducer

51 51 ESMR treatment set-up

52 52 Case Study Evaluation by SPECT

53 53 Pre treatment Post treatment

54 54 Extracorporeal Shockwave Myocardial Revascularization Current clinical indications

55 55 ESMR clinical aim Induce local angiogenesis at myocardial ischemic areas using low intensity, non invasive, focused shock waves Treatment option for patients who no longer benefit from current revascularization methods Angioplasty CABG ESMR

56 56 Treatment of end-stage Coronary Artery Disease Patient: 62, male, 3-vessels disease, post MI, CABG X 2,, PTCA & Stent. Pre - Treatment Post - Treatment Pre: CCS class IV Post: CCS class III *Courtesy of Prof. R. Erbel, Essen, Germany

57 57 Treatment of 3-Vessel Disease Patient: 75 yo male, DM, HPT, Dyslipidaemia, Smoking, 3-vessel disease, prior PCI, CABG Pre - Treatment Post Treatment 6-month follow-up Stress Rest CCS class: 3-2, SAQ: EST duration: , METS: LVEF: 24-46, TDI: *Courtesy of Prof. Wan Azman,Kuala Lumpur, Malaysia

58 58 Improvement of regional perfusion Improvement of regional myocardial blood flow (assessed by PET scan) P=0.9 P=0.04 Faber et al. 2010

59 59 Chronic Heart Failure Study Minnesota Living with Heart failure Nitroglycerin doses per week p=0.01 p<0.01 Left ventricular ejection fraction p=0.03 Vasyuk et al.2010

60 60 Long-term results NTG uptake/hospitalization - 1 yr follow-up 90% 80% 70% NTG HOSP 60% 50% 40% 30% 20% 10% 0% Pre ESMR 1 month 3 month 6 month 1 Y Alunni, 2011 Gutersohn A, 2006

61 61 Increase of Exercise Tolerance Capacity Yaakob Z, 2011 Panaeva S, 2010 Fu M, % 28% 29% Mean improvement (*) 34% Leibovitz D, 2010 Vasyuk Y, 2010 Vainer J, % 33% 35% Faber L, % Koltunov I, % Samad A, % Lyadov K, 2006 Naber CK, % 64% 0% 10% 20% 30% 40% 50% 60% 70% (*) Different analysis methods (**) n=240

62 62 Decrease of Weekly Nitrate Intake Mean improvement 79% Panaeva S, % Nikonenko A, % Zuoziene G, % Vasyuk Y, % Vainer J, % 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% * n=201

63 63 Improvement of Myocardial Perfusion Mean improvement (*) 33% Yaakob Z, % Alunni G, % Vasyuk Y, % Faber L, % Takayama T, % Naber CK, % 0% 10% 20% 30% 40% 50% 60% (*) Different analysis methods (**) n=114

64 64 Safety Troponin I levels (n=78) Troponin I ng/ml baseline 1st 2nd 3rd Therapy course Normal Values < 0.1 ng/ml Average values Faber L. (2008), Vainer J. (2008), Takayama T. (2008), and Samad A. (2008) reported no change in cardiac markers between baseline and post treatments

65 65 Summary Extracorporeal Shockwave Myocardial Revascularization Non-invasive treatment for patients with myocardial reversible ischemia untreatable by conventional methods Triggering local angiogenesis in the treatment area Painless, safe treatment without reported side effects

66 66 Shock wave theory of operation Shockwaves are being successfully used around the world since 2005 to treat reversible ischemic tissues in the heart, thus inducing neovascularization and developing new collaterals. This improves the volume of blood flow into the tissue. The same modality is used for treatments for vascular-based Erectile Dysfunction problems.

67 67 Rational behind EDSWT Extracorporeal shockwave treatment promote endothelial cell precursors Extracorporeal shockwave treatment enhance expression of vascular endothelial growth factors and its receptor. Extracorporeal shockwaves clinically induces neovascularization which improves tissue perfusion. ED is a disease of the endothelium. Extracorporeal shockwave treatment can be used for treatments of vascular-based Erectile Dysfunction.

68 68 ED1000 system

69 69 The ED1000 system Low intensity Extracorporeal Shock waves especially designed for the treatment of Erectile Dysfunction

70 70 Device Description SWA Holder Shockwave Applicator (SWA) Handles Control Panel Retractable Wheels Shock Wave Power Unit Cabinet Dimensions: height: 740 mm x width: 775 mm x depth: 410 mm; Weight: 35 kg

71 71 Device Description "Umbilical Cord" SWA supporting Arm Port Mains Connection, Footswitch Connection & Master Switch

72 72 Control Panel ON/OFF Switch LCD Touch-Screen & Display

73 73 Treatment Screen High-Voltage Indicator Operate Key Shockwave Indicator Applicator Indicator General Warning System Status Indicator Time & Date Display Return Key Service Screen Information Key

74 74 Number of Shocks selection Treatment Counter Reset Numerical Keypad Activation Countdown Key

75 75 Number of Shocks selection Down Counter display Countdown Value Number of Shocks selected

76 76 Messages -Applicator is not Properly Connected

77 77 Messages-SWA Applicator Out of Range and must be Replaced

78 78 Messages-Incorrect SWA Applicator

79 79 Messages Hardware or Operational Software Failure!

80 80 Information Screen Number of Shocks performed by the Device ED1000 Serial Number SWA Serial Number Number of Shocks left in the SWA SWA Expiration date

81 81 Service Screen requires password! Press Return Key to exit.

82 82 System features & benefits Plug & play No special electrical requirements. User-friendly Touch screen control panel. Shockwaves countdown. Portable Cost-effective Applicator Compact Easy to move Easy to store. Quick operator training. Low cost maintenance. Applicator is the only consumable When needed, applicator replaced entirely

83 83 Treatment method

84 84 Treatment methods EDSWT is applied on the penile shaft and corpus. Each treatment included a 3-minute application of 300 shock waves in 5 different anatomical sites.

85 85 Technique Shaft Crura

86 86 Penis Anatomy

87 87 Penis Anatomy

88 88 Treatment of the shaft 1. Stretch the penis. 2. Firmly attach shockwave applicator to the treatment location with the SWA center perpendicular to the shaft. 3. Apply 300 shocks at three locations across the shaft (below the gland and above the base). 4. Use generous amount of coupling ultrasound gel.

89 89 Treatment of the crura 1. Locate the pubic bone of the patient. 2. Deliver 300 shocks beneath the pubic bone with the SWA center toward the crus as indicated on the picture. 3. Repeat the procedure on the other side with additional 300 shocks. 4. Use generous amount of coupling ultrasound gel.

90 90 Treating the Cruz: a look from the side

91 91 Treating the Cruz: patient lie down

92 92 Treatment protocol Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 Week 9 Per Patient: 2x6 treatments drg. 9 weeks 5 treatment zones 300 shocks per zone 18,000 shock Total Treatment Time: 20 minutes

93 93 Air bubbles During shock wave discharge air bubbles are created and accumulate within the SWA membrane Air diminishes propagation of shockwaves in the body Air can be detected by the following means: Sound with air accumulation the shockwaves sound becomes metallic Sight air bubble is visible when turning the SWA upside down

94 94 ED1000 unique advantages Novel treatment option for patients with ED offering real cure No use of medications No reported side effects Use on demand Therapeutic angiogenesis using shockwaves

95 95 ED-1000 Installations

96 96