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Genesee Bird And Pet Clinic Conventional and Alternative Medicine and Surgery 5621 Balboa Ave. # San Diego, Ca 92111 # Ph (858) 278-1575 # FAX (858) 278-1551 THE USE OF OZONE AND OXYGEN THERAPY IN VETERINARY MEDICINE Robert Smatt, DVM, MS I History of Ozone in Medicine The discovery of the chemical known as ozone gas in 1840 is credited to Christian Schonebein, a professor of physics and chemistry at the University of Basel. Professor Schonbein also invented guncotton (methylcellulose) and explored the use of hydrocyanic acid to stop meat putrefaction, demonstrating the possibility that meat could be preserved for long periods of time. This was a large leap forward in our thinking about oxidative processes. During the time of his studies of meat preservation, he contracted anthrax. He died on August 28, 1868. While he also advocated the use of ozone as a possibility for the control of infectious diseases, he was unable to use it to stop his own ultimately deadly infection. Some eleven years after Schoenbein’s death the chemist Werner von Siemens invented and patented the ozone “super induction tube”, a means of generating ozone. This was an important step forward in the use of ozone gas because it recognized the fact that because the gas is unstable, unstorable, and highly reactive, it needs to be generated ozone immediately before its use. Among the first uses of ozone was the disinfection of water. Today more than 2500 cities throughout the world use ozone in the water purification process. These cities include Los Angeles, Montreal, Moscow, Kiev, Paris, Amsterdam, Singapore, and Florence to name a few. The first ozone generator devised for medical use was made several decades after Siemens invention. It was devised by a physicist named Joachim Hansler (1908-1981). His company’s device greatly enhanced the spread of the use of ozone in medicine. Another critical step in the use of ozone in medicine is that of a photometric device for measuring the concentrations of ozone. Without such a device, the safety of various concentrations of ozone could not have been established. Born in 1871, the Austrian surgeon, Edwin Payr, became acquainted with ozone when it was used on him by his dentist, E.A. Fisch. Dr Fisch applied for a patent on an ozone generator called “Cytozon,” now used in medical ozone generators today. Dr Payr became so enthusiastic about medical ozone that he ultimately published a 290 page book entitled, “On Treatment with Ozone in Surgery,” which he presented to the German Surgical Society in Berlin. This was the beginning of the use of ozone in medicine as we know it today. Medical ozone was used during the First World War to treat gangrenous wounds of German soldiers. Dr P. Aubourg, a French physician was the first to publish a paper in 1936 on infusion of ozone rectally in the treatment of chronic colitis and fistulae. In the 1940’s autohemotherapy, the administration of a small quantity of the patient’s ozonated blood began. The use of medical ozone was developed and is accepted in Germany. It is tolerated by France, England, Italy, and Canada, and 14 states in the United States. There is still some concern as to the legal status of medical ozone with regard to the United States Federal laws. Today the use of ozone in medicine and most of the research in medical ozone takes place in Cuba and Russia. In fact, ozone therapy is in the medical mainstream in Russia, and especially Cuba. II Why oxygen and ozone therapy? Before we can talk about ozone (O3), we must talk first about oxygen (O2), from which ozone is formed. The oxygen we breath originates primarily from two places—the plankton of the sea and the new growth of forests. An oxygen molecule (the smallest amount of a chemical substance that can exist without further breaking down) is composed of two oxygen atoms, called O2. Fossils encased in amber, many thousands of years old, contained bubbles which when analyzed, were found to contain 30% O2. Presently, our atmosphere contains 21% O2. In cities that are badly polluted this percentage is reportedly around 15%. Oxygen content of the air in Gary, Indiana with its steel mills and blast furnaces has been measured at 9-11 %. At 7% O2 mammalian life ceases. Oxygen carries and ultimately stores the sun’s energy so that all life can feed on it. Oxygen is the most abundant element of the earths crust. It easily dissolves in water. Oxygen compounds form a major part of the elements in the oceans, rocks, and all living things. Oxygen makes up 65% of the elements of our body tissues such as blood, organs, tissues, and skin. All organisms (microbes, animals, and plants) have spent countless centuries swimming and evolving in or are contained in a sea of water and oxygen. It is these two molecules, oxygen and water, which support the milieu of all the chemicals which make up all the cells held together to interact and react to create and maintain life. Oxygen is absolutely essential for the health of cells. It removes toxins from the body and is the key element in the “combustion” of glucose molecules (the primary mammalian energy source) to produce energy in the form of ATP, the bodies primary form of stored energy at the biochemical level. When glucose is metabolized to ATP anaerobically, six ATP molecules are produced. When the same molecule of glucose is metabolized in the presence of O2, thirty eight molecules of ATP are produced. Our personal energy can suffer from lack of exercise. The brain, comprising 2% of human body mass, requires 20% of the bodies oxygen needs. Exercise increases circulation and therefore the delivery of oxygen to cells. Many centuries ago Chinese physicians proclaimed stagnation to be the root of all ill health. It is of interest to note that the effectiveness of treatment modalities in Chinese medicine such as cupping, moxibustion, and bleeding is due to the fact that they bring increased circulation of blood and therefore increase oxygenation of tissues. In a room full of people, we know how uncomfortable we get, and seek larger open spaces or moving air for relief from this discomfort. This discomfort is due to excessive amounts of CO2 in the air. Many temporary maladies, such as headache, fatigue, eye, nose, and throat discomfort have been shown to be caused by high CO2 levels in airplane cabins. These same symptoms promptly disappear upon departing the aircraft and breathing more oxygenated air. In 1966 the Nobel Prize winner Otto Warburg demonstrated that the key condition for the formation of cancer is lack of oxygen at the cellular level. Almost every virus, fungus, parasite, and many bacteria such as Lactobacilli, Campylobacter, Clostridium, and Bacteroides are facultative or strictly anaerobic----they do not thrive in oxygenated environments. As time goes on, we are finding more and more microorganisms associated with cancer. These are bacterial, viral, and parasitic forms of life. Water is the other basic element which contributes to stagnation and lack of oxygen. It takes adequate hydration of the body to transport oxygen, especially to the brain. Again, stagnation, which translates into lack of oxygen, is the major cause of disease. Naturally Occurring Ozone A single molecule of oxygen, also known as singlet oxygen (one oxygen atom with a negative charge) is highly unstable, only able to exist for microseconds in nature. When two single oxygen unite to share electrons, they unite to form the very stable O2 molecule found in nature. When O2 molecules are exposed to an energetic force such as electricity or ultraviolet light, they temporarily split apart and reform into O2 molecules but now with a small percentage of oxygen molecules forming ozone gas. This new O3 gas is unstable and interacts with other ozone molecules, and breaks down into more stable oxygen O2 molecules once again. The half life of ozone is 45 minutes in glass, 30 minutes in plastic. Chemical Structure of Ozone Ozone occurs naturally in the atmosphere, and at about 20 Km (12 miles) above the earths surface, the concentration of ozone in the ozone layer is about 10 parts per million according to Velio Bocci, the foremost researcher in the field of medical ozone. Renate Viebahn-Haensler, another authority on medical ozone, states that at a height of 20-30 Km the concentration of ozone is 1000mcg/cubic meter. If we could maintain a constant temperature of 273 degrees K and a pressure of 101 kPa, the thickness of the ozone layer would be only a few millimetres thick. It has been estimated that a 10% drop in the concentration of the ozonosphere would result in a 25% increase in skin melanomas and carcinomas. This protective aspect of ozone is because it acts as a shield. This shielding effect is due to the UV light acting upon oxygen, O2, to form ozone, O3. While ultraviolet light favours the formation of ozone, nitrogen oxides and chlorine, air pollutants, destroy significant amounts of ozone. The knowledge that chlorine destroys ozone dates back to 1900. The concern then was because of chlorides from volcanoes. In 1974, the problem of chlorinated fluorocarbons (CFC’s) was discovered. CFC’s are transported into the stratosphere where they are acted on by UV light releasing free chlorine which destroys the ozone layer. The hole now over Antarctica is 3.5 times larger that the United States. During winter in Antarctica temperatures as low as minus 80 degrees C allow formation of thin ice clouds which activate chlorine, which in turn destroys ozone more efficiently than anywhere else. Hole in the ozone layer over Antarctica At street level, the situation is reversed. Man made atmospheric emissions such as carbon monoxide, nitric and nitrous oxide, methane, and sulphur compounds, act as catalysts in the production of ozone. At the earth’s surface, the troposphere, the ozone concentration should be lower than 40 parts per billion. In many large metropolises such as Mexico City, Florence and Milan Italy, ozone reaches toxic levels, especially during the summer. The Safety of Ozone There is no doubt that ozone is very toxic to the respiratory tract, because respiratory tract lining fluids have little protective capacity from ozone. Ozone, however, has come to be emphasized as the major cause of lung damage due to air pollutants even though other air pollutants such as sulphur and nitrous oxides do far more damage than ozone. This is because atmospheric ozone concentration, being very easy to measure, has become the standard measure by which we monitor air pollution. The World Health Organization states that it is permissible to work for 8 hours in an ozone concentration of 0.6 ppm (120mcg/cubic meter or 0.12 mcg/litre). There is a wealth of literature available on the health hazards of ozone, but almost every reference refers to the toxic effects of ozone on the respiratory system. The medical use of ozone has a safety history that is unprecedented in modern medicine. Dr Bocci states that from 1950 to 1986 in central Europe there were no “untoward effects” in 340,000 ozone treatments. In an article by M. Jacobs (Ozonachrichten 1986; 5:1-5), the records of 384,775 patients treated with different ozone modalities for a variety of medical conditions were examined. There were 5,579,238 treatments administered to these 384,775 patients with an incidence of “accidents” of 0.0007%, or 39 “accidents” in absolute numbers. This is a safety margin far greater than that of aspirin. Most of these treatments were major autohemotherapy, the intravenous auto infusion of ozonated whole blood, a technique which we will describe later. Four of these accidents were fatalities, all of which resulted from infusion of ozone gas directly intravenously. Direct IV therapy of ozone should never be used. It results in free radical damage, pulmonary embolism, bronchial constriction, pulmonary failure, cardiac arrhythmia, phlebitis, and hypoglycaemia. Needless to say this form of administration of ozone is forbidden. These phenomena have been well documented in dogs and humans, pre and post mortem. In horses, however, ozone gas has been introduced directly intravenously, reportedly without any of these adverse effects, at least on a gross pathophysiological level. The following is a summary of the toxic effects of ozone in humans according to Dr Velio Bocci, the foremost researcher in the use of medical ozone. At 0.1ppm lachrymation and irritation of upper respiratory airways occurs. At 1.0-2.0 ppm we see rhinitis, cough, headache, occasionally nausea and retching. From 2.0-5.0ppm for 10 to 20 minutes of exposure (inhalation) progressively increasing dyspnoea, bronchial spasm and retrosternal pain occur. Breathing 5.0 ppm (0.01 gamma) for 60 minutes causes acute pulmonary edema and occasionally respiratory paralysis. Breathing 10ppm (0.02 gamma) for four hours will result in death. Breathing 50ppm (0.1 gamma) ozone will cause death in minutes. Frank Shallenberger, M.D., a pioneer in the use of medical ozone in America, states that one must inhale an ozone concentration of 20 gamma for over one minute to cause permanent lung damage. Just one breath or even a sniff of 20 gamma ozone will lead to severe coughing spasms. More than one inhalation is physically impossible, let alone a 60 second exposure. Our ozone perception level (the concentration at which we can smell it) is 0.02mg/cubic meter = 0.02mcg/l or 0.0002mcg/ml (gamma) or 0.1ppm. The average therapeutic concentration of medical ozone used in treatments is 37gamma or 37 mcg/ml. It is obvious that medical ozone treatments must be carried out in a well vented facility. Concentration Calculations Some ozone concentration conversions are given below for those wishing to calculate ozone concentration numbers in mcg/ml or gamma. 0.1ppm=0.2mg/cubic meter=0.2mcg/l=0.0002mcg/ml 1.0ppm=0.002mcg/ml 1000ppm=2.0mcg/ml 10,000ppm=20mcg/ml Another way to state ozone concentrations is that 0.5% ozone is equal to 7 mcg/ml, 1.0% is equal to 14mcg.ml and so on up the scale. Micrograms per millilitre or gamma, is the common unit used in determining proper treatment concentrations of medical ozone. Concentrations of ozone used in therapy commonly range from 20 to 80 gamma. The bottom line however, is that as long as ozone is used according to the guidelines previously mentioned and described later under forms of therapy, it is one of the safest modalities in medicine. III How ozone works in the body The gaseous substance we call medical ozone is actually a mixture of primarily pure oxygen (95.0 to 99.5%) and a small amount of ozone (0.55.0%). Hereafter when we use the term ozone, we are referring to medical ozone. It is well accepted that many diseases, whether acute or chronic, are characterized by free radical oxidant stress, causing patients to suffer from poor energy production and fatigue. Consequently, all patients with chronic oxidant stress are observed to improve when oxidant therapy is administered. Then how does the introduction of ozone become a positive therapeutic event? Organs and cells affected by ozone therapy Free Radical Production- a review of the processes of oxidation and reduction and the production of free radicals. Most biological molecules have two electrons in their outer orbit and are stable. Free radicals are substances that contain one electron in the outer orbit and are unstable and reactive. There are three ways a free radical can react with other chemicals. It can extract an electron from another molecule (be reduced), it can react with another free radical forming a stable covalent bond, or it can donate its electron to another molecule (become oxidized). As a consequence, the new molecules formed in turn become free radicals and must in turn go about extracting or sharing electrons, thus forming still more free radicals. These reactions are enhanced by ions of iron, cobalt, copper and nickel (commonly increased for instance in the haemolysis of blood). Sources of free radicals are viruses, bacteria, parasites, normal respiration and metabolism, exposure to pollutants, exposure to the sun, xrays, injury, and stress to name a few. Naturally occurring free radicals are nitric oxide (NO), hydroxyl ions (OH-), and the oxygen anion (O-), also known as singlet oxygen, the latter resulting from the breakdown of the ozone molecule. Oxidative Stress and Imbalances 1) Normal conditions of health and Rest 2) Decreased Antioxidant Production without Increased ROS 3)Marked Increase in ROS Overwhelms Normal Antioxidant System 4) Both a Reduction in Antioxidants and Increase in ROS 5) Excess intake of vitamin c can lead to oxidative stress. The site of free radical production takes place at the mitochondrial level from either ischemia (less O2) or excessive functional demand on the cells (again poor oxygen utilization). When ozone enters the water fraction of plasma, its first order of preference is to attack lipids, especially polyunsaturated fatty acids (PUFA’s). Second it is neutralized by antioxidants such as vitamin E, C, glutathione, bilirubin, cysteine rich proteins and carbohydrates. PUFA’s are found in cell walls and membranes, lipoproteins, triglycerides, and chylomicrons. As a result of this ozone-lipid reaction, ozonides, peroxides, aldehydes, and other free radicals are formed. These free radicals damage cells by literally punching holes in them (damaging the cell membrane), and damaging DNA. Ozone, not a free radical itself, does not cause significant free radical damage when introduced into the body because 1) Ozone is introduced in small quantities relative to the amount of tissues present in the body (blood is considered a tissue) 2) Immediately upon entering the body, ozone reacts with tissue chemicals such as PUFA’s, vitamin C, glutathione, etc mentioned above. 3) Ozone is never administered directly into the bloodstream. 4) The byproducts of ozone-tissue chemical reactions are readily metabolized by the liver and kidneys. The ozonides and peroxides formed by ozone-lipid contact are not toxic as is ozone when directly contacting tissues. It is for this reason that ozone bubbled through olive oil by a diffuser can be used in inhalation therapy without causing damage to the respiratory system. 5) As mentioned above, ozone itself is not a free radical, for it has paired electrons in its outer orbit. It is, like water, a magnetic dipolar molecule, represented by the chemical picture O=O-O, involving an ionic bond. The magnetic potential of a dipolar molecule prevents the formation of free radical in aqueous environments of pH less than 8, a pH not found in the body. However, as the ozone molecule reacts with substances in the body, such as reduced glutathione, it gives rise to an unstable O3 molecule which ultimately results in the generation of a hydroxyl radical, the most potent oxidant known in chemistry. A general synopsis of the positive effects of the introduction of ozone into biological systems Paracelsus was the first physician to observe that like cures like. For example, vaccines (the injection of microbes) kill microbes by stimulating a process that allows the body to eradicate the offending microbes. And so it is with ozone. The Arndt-Schultz phenomenon states that a substance is stimulating in a small dose, modulating in a larger one, and suppressive in a still larger dose. And again, so it is with ozone. Finally, the state of free radical oxidant stress is caused by a lack of free radical buffering ability that is really the cause of the build-up of excess free radicals. Ozone “turns on” the free radical buffering systems and remedies this problem. When we take these three statements together, we find that ozone therapy offers a very effective solution to health problems. When correct doses of ozone are given, it stimulates free radical buffering systems, it can kill bacteria (bactericidal), viruses(virostatic), fungus(fungicidal), and parasites(parasiticidal), and it stimulates the production of all the cytokine systems of the body, specifically interleukin -2 ( secreted by T helper cells), interferon, and tumour necrosis factor, and stimulates the production of white blood cells. Thus, it eliminates microbes by direct kill and indirectly as in the vaccine example. In a paper published in early 2004 in the journal “Science”, a group of researchers from Scripps Institute in San Diego, California, has demonstrated that all antibodies appear to make ozone. In addition to being valuable in antimicrobial therapy, ozone breaks down petrochemicals, increases the flexibility and elasticity of red blood cells, and oxidizes arterial plaque. Very importantly, it increases the red blood cell enzyme 2, 3 DPG, which catalyzes the release of oxygen from red blood cells into tissues, and very importantly, accelerates the Krebs or citric acid cycle. We will discuss this last and very important benefit of ozone below. Ozone and the Production of Energy The feature characteristic to all chronically ill patients is that they produce insufficient energy. This is seen as a lowered core body temperature, decreased ATP production, and lowered basal metabolic rate. Assuming that there is normal cardiopulmonary function and no anaemia, possible causes of deficient energy metabolism are 1) increased fibrin accumulation in capillaries due to abnormal clotting from immune causes 2) decreased cellular uptake of substrates of fat and glucose, due to chronic insulin excess secondary to insulin resistance. (This is always a problem in diabetics and persons over 50 years of age.) 3) Mitochondrial dysfunction, where glucose metabolism takes place. Mitochondrion Energy in the body is derived from fats, carbohydrates (glucose), and proteins, but no matter the source, products of their metabolism ultimately end up in the citric acid cycle. The amount of energy released from one mole (180 grams) of glucose is 686,000 calories. Of these, 230,000 calories are used for heat and 456,000 calories can be stored in the form of ATP, adenosine triphosphate, the primary energy currency of the body. ATP is present everywhere in the cytoplasm and nucleoplasm of cells. Essentially all physiological mechanisms that require energy obtain it from ATP and another high energy phosphate, guanosine triphosphate. There are two high energy phosphate bonds per ATP molecule, and the energy released from one of these high energy phosphate bonds under normal body conditions is 12,000 calories. There are four phases of glucose metabolism in the production of energy in the form of ATP. Two Forms of the Glucose Molecule The first stage is glycolysis, which yields pyruvic acid and 2 molecules of ATP from each molecule of glucose and releases four hydrogen atoms. The next stage is the formation of acetylcoenzyme A, accomplished by combining the pyruvic acid with coenzyme A, a derivative of pantothenic acid. This reaction forms no ATP but releases four hydrogen atoms, which later are used to create more ATP in the citric acid cycle and electron transport chain. Citric Acid Cycle Acetylcoenzyme A initiates the citric acid cycle. The citric acid cycle releases sixteen hydrogen atoms. These hydrogen atoms must be transferred through the eight steps of the citric acid cycle. This is carried out by nicotinic adenine dinucleotide (NAD+). Each NAD+ is converted to NADH in three steps of the citric acid cycle. FAD is converted to FADH2 in step six of the cycle similar to the production of NADH. Buildup of pyruvic acid (caused by inadequate oxygen) and NADH stop the glycolytic process. For each molecule of glucose the citric acid cycle occurs twice, giving the net production of two more molecules of ATP. Electron Transport System FAD and NAD are supplied by oxidative phosphorylation, the major source of energy production in the body. This catalyzes the reduction of hydrogen and formation of water, releasing ATP. NADH and FADH2 are supplied by the citric acid cycle, and thus oxidative phosphorylation and the citric acid cycle are mutually dependent. When one system slows down, so must the other. In chronically ill patients it is found that there is a lowered NAD/NADH ratio signifying a blockage, so to speak, at the level of oxidative phosphorylation. By using ozone to oxidize NADH to NAD and FADH to FAD increased levels of coenzyme A are available to fuel the citric acid cycle and oxidative phosphorylation. Some studies have shown a total increase of 40% in ATP production after ozone therapy and an increase in lowered NAD/NADH ratios found in all ill persons. It should be noted that the best source of acetyl CoA is from fat metabolism. Acetyl CoA only lasts 2 hours in the system. As we grow older, fat metabolism becomes more inefficient and we burn glucose instead to form acetyl CoA. Glucose is more easily exhausted and thus so is the older patient who complains of brain fatigue. Also, the brain can only generate acetyl CoA from glucose, not from fat. Decreased mitochondrial function may be caused by insufficient coenzyme A production from glucose resulting in the accumulation of excess lactic acid responsible for the tiredness and acidosis of the chronically ill. There may also be decreased coenzyme A production via fat metabolism. Insufficient coenzyme A leads to the suppression of the citric acid cycle. Also, a decrease in oxidative phosphorylation can be initiated by viruses, heavy metals, pesticide and petrochemical sensitivity, and autoantibodies. By oxidizing NADH and FADH2 to NAD and FAD, medical ozone can correct all these mitochondrial lesions. This process is best carried out by Major AutoHemoTherapy (MAHT). During glucose breakdown from glycolysis through citric acid cycle, 24 hydrogen molecules are released. Twenty of these hydrogen molecules are converted to ATP by oxidative phosphorylation in the chemiosmotic process of the electron transfer system. During this process, up to 3 ATP molecules per each 2 hydrogen molecules are released, generating an additional 30 ATP molecules. The remaining four hydrogen molecules are also released into the chemiosmotic system to generate 4 more ATP molecules. In total, from glycolysis, acetylcoenzyme A production, the citric acid cycle and the electron transfer system, 38 molecules of ATP are formed from each molecule of glucose being processed by this four step process. The citric acid cycle also is oxygen dependent. Without oxygen the citric acid cycle cannot be completed. More importantly, without oxygen, the initial step of acetylcoemzyme A production from pyruvate cannot happen. In the absence of sufficient oxygen, pyruvate is turned into lactic acid instead of forming acetylconezyme A, a process which to generates only 6 molecules of ATP and does not allow the utilization of glucose to proceed through the citric acid cycle and the electron transport process. Another way in which ozone exerts its therapeutic effect is the activation of the immune system. Here we see the physiological release of cytokines (interferones, interleukins, and tumour necrosis factor). It has been shown that the dose of ozone responsible for maximum release of cytokines is 78 gamma. This suggests that ozone has an indication for diseases accompanied by an immune deficiency, such as an additional therapy for types of cancer. Ozone also activates red blood cells by increasing ATP and 2, 3 diphosphoglyerate which more readily allows oxygen to be released from haemoglobin and thus more available to tissues. Here the indication for ozone could be for any circulatory disorder, peripheral or central (e.g. cerebral arterial). Another group of chemicals activated by ozone are enzymatic antioxidants and radical scavengers such as super oxide dismutase, catalase, and reductase, are induced and activated, thus increasing the organisms antioxidative capacity. The mechanism of this process has been shown to be the enhancement of the glutathione peroxidase system. The glutathione peroxidase system is primarily responsible for the antioxidant buffering system of the body, although we also have superoxidases, catalases, and reductase. Increased production and enhancement of these systems is stimulated by treatment with ozone. In this scenario, vitamin E and C can only support these antioxidant buffer systems but by themselves cannot correct the basic lesion. Therefore ozone is beneficial for treating inflammatory processes such as arthritis, strained muscles, trigger points, vascular diseases, and aging. Ozone also directly kills microorganisms, as already mentioned. I have been asked the question, “Could these phenomena be due to oxygen alone?” The answer is no. Research has shown that only the addition of ozone will cause or enhance the above mentioned phenomena. IV Techniques in the Administration of Medical Ozone Major Autohemotherapy Major autohemotherapy is the major form of systemic ozone application. The reaction mixture of ozone and the patient’s whole blood takes place extracorporeally and is infused back into the patient, containing activated and lysis resistant enhanced red blood cells and activated immunocompetent cells. Blood is removed from the patient, 50 to 250 ml in humans, 25 to 100ml in dogs and cats, and 250 to 1000 ml in the horse. Most practitioners use an aliquot of blood collected in heparin. Calcium chloride is added to the heparinized blood as calcium ions enhance the action of ozone. The heparinized blood is combined with an equal amount of medical ozone at 70 to 80 gamma concentration. (Hemolysis of only 0.2-0.5 percent of total red blood cells occurred when human whole blood was exposed to 100gamma ozone.) This solution is then mixed by gentle inversion. According to Dr Velio Bocci, the period of mixture of blood and ozone should be done for at least five minutes to be most effective. This blood- ozone mixture is infused back into the patient as with any other blood infusion or transfusion. Collection and administration of blood is best done in glass bottles or syringes. It has been shown that the number of plastic particles is increased dramatically in ozonated fluids collected in plastic containers. In dogs and cats, I often infuse the ozonated blood back into the patient by injecting it intraperitoneally instead of intravenously. This route of administration seems to be equally effective. This procedure is repeated every one to seven days depending upon the condition. This procedure should greatly enhance surgical healing and anesthesia recovery when done before and after surgery. In general, an obvious and immediate increase in vitality, appetite, and competitiveness is noted in people, dogs, cats, and horses Case History: Beth Lang, 6 years old Malamute, Hepatic cirrhosis and cadmium intoxication resolved using major autohemotherapy SGPT ALK PHOS GGT T.BILI 2/29 3014 3309 245 1.2 3/12 2769 2865 161 2.8 4/1 3314 3250 45 4.8 4/21 3543 1918 27 2.1 5/11 2213 1103 26 1.4 6/6 1329 810 23 1.7 7/11 449 508 12(N) 2.0 379 ? 0.71(N) Date (Returned to internist 8/1) 8/2 357 Case History: Angel Kahn - 10 year old female sheltie Treatment: Rectal Insufflation only Cushing’s Disease + Terminal Kidney Failure Pre O3/5-25 Post O3/5-29 BUN PostO3/6-15 107 79 64 Creatinine 9.1 2.7 2.3 Phosphorus 8.6 8.2 6.9 Rectal Insufflation Equipment needed: a rectal inflation bag or a large 12 to 150 cc syringe depending upon the size of the animal patient to act as ozone reservoirs or delivery systems, and polyvinyl female urethral catheter(12 gauge 18 inch works well for humans) again depending upon the size of the patient. Most small animals take a 12 gauge, 8-16 inch polyvinyl urethral catheter. Small cuffed endotracheal tubes and various diameter Foley catheters also work well in small animals. Ozone concentration should be 20-30 gamma. Dogs will take 20 to 150 ml volumes of ozone comfortably, depending on their size. Infusion is best preceded by an enema, although an enema is not entirely necessary. Cats comfortably take up to 25 ml. Ozone should be retained for 40 minutes to be effective. We use rectal infusions for 80% of our small animal and equine patients, and could easily justify its use in 100% of all medical and surgical problems. It is very well tolerated (accepted by both animals and their human companions). Invariably there is an immediate increase in vitality and appetite after the first administration. Vision Map of Retina with Retinitis Pigmentosa Minor Autohemotherapy Fill the syringe with a volume of 37 gamma ozone equal to the amount of blood to be injected. Draw the blood into the syringe with gas and mix them gently for at least 30 seconds (I try for at least one minute and have gone up to five minutes without the blood clotting). Remove the dead space left by the gas and inject the blood only intramuscularly. Inject 3 to 12 cc of blood in cats and dogs, depending upon the size of the patient. I have also injected the blood intraperitoneally. By the intraperitoneal route the amount of blood injected can be much larger and the blood and gas can mix longer without danger of causing clotting problems. Limb Bagging Extremities are placed in limb bags specially made for this process or standard trash bags can be used to encase the limb being treated. The bag is wrapped from distal to proximal with an ace bandage to expel air and sealed at the top with tape. The ace bandage is removed and the bag is filled with ozone (80-90 gamma for infection, 40 gamma for wound healing. The gas is retained for 30-40 minutes. Treatments are one to two times per day. Ozone in Water Ozone is very soluble in water. Eighty gamma ozone is bubbled through a column of double distilled water with a diffuser at a flow rate of 125ml per minute for 25 minutes. This will give a concentration of 30mcg ozone per ml of water. At room temperature it has a half life of 10 hours. Refrigerated it has a half life of 24 hours. Using mono-distilled water will decrease the half life to only a couple of hours. The latter is great for drinking. Ozone in Saline Using the diffusion technique, as above for water, higher concentrations of ozone can be achieved in saline. This is advantageous because physiological saline is kinder to tissues and can be used to instil into the bladder, vagina, ears, rectum, and eyes. It can be used for irrigation of large surface wounds to vastly increase healing rates. It can also be injected into necrotic tissue. This solution can also be given intravenously. Ozonated saline is excellent for flushing chronically infected nasal passages and sinuses in cats following viral infections to abort chronic sinusitis. 37 gamma ozone is used for sensitive tissue surfaces. Ozone Directly into Joints Thirty seven gamma ozone is injected directly into the joint via a 25 ga ¾ or 1 ½” needle depending upon the size of the animal. The injection is directed even more point specifically if the ozone is to act as a proliferative agent for prolotherapy. For instance in the case of cruciate ligament tears or patellar luxations the specific targets for injection are the cruciate ligaments, the femoropatellar ligament, and the medial and collateral ligaments. These injections can be preceded by 2% lidocaine which will cause little to no pain reaction when the ozone is introduced. Immediately after injection the patient may favor the involved limb for a few hours followed by improvement in the condition. Pet owners should be made aware that this will occur. Cruciate ligament tears should be treated once to twice weekly for two to three weeks. Prolotherapy/Sclerotherapy 37 gamma ozone should be used as a proliferative agent for sclerotherapy. The treatment may or may not be preceded by a local anaesthetic depending upon the sensitivity of the patient. Acupuncture (ozone-puncture) Ozone used at acupuncture points has given me better results than aqua puncture using vitamin B12 at the same points for the same condition. For instance, K3, UB 60, Du 1, Ren 1, Ren 3, UB40, UB 36, and the ba liao points work much better to control urinary incontinence in dogs using ozone gas injections than does the same treatment using vitamin B12.`37 gamma ozone is used. Trigger Point Injection and Muscle Spasms, especially Quadratus lumborum and Iliopsoas muscles Inject one to two cc’s of 37 gamma ozone into trigger points, motor points, and along the entire length of palpable muscle spasms. There is no more pain than experienced with the injection of local anaesthetics into a muscle; therefore, no preinjection with local anaesthetics is necessary. There will be only momentary pain immediately after the injection. One to two injections two to three days apart should be all that is necessary to resolve these myofascial pain regions. Ozone in Olive Oil Ozonated olive oil is very effective when used topically for any skin condition such as eczema, herpes, fungal dermatitis and paronychia. For topical application it is best made by bubbling 40 gamma ozone through olive oil in a column via a diffuser at the bottom for 36 hours until it reaches the consistency of Vaseline. Eye drops which are used for treating corneal ulcers and conjunctivitis can be made by bubbling 40 gamma ozone through olive oil for about one hour. Inhalation While ozone is very toxic to the respiratory mucosa, it can be bubbled through olive oil which causes the production of peroxides and ozonides that are non toxic to the respiratory epithelium. Subconjunctival injection Twenty gamma ozone is injected into the sinuses or subconjunctivally for chronic conjunctivitis and as an aid in the treatment of indolent corneal ulcers. Tonsilitis One injection of 37 gamma ozone usually resolves chronic(or acute)tonsillitis. The patient must be anesthetized. For some reason, probably the embryonic connection of stomodeal and proctodeal membranes, Injecting tonsils with 37 gamma ozone will usually resolve chronic colitis. Gingival and Tooth Apex Injection This is the area where the gingival meets the buccal mucosa. First inject ½ to 1 cc of an appropriate local anaesthetic into the area corresponding to the root of the tooth you are treating. This is followed by one to five cc of 33 gamma ozone into the same area. Here we are treating osteomyelitis and are essentially eliminating the need for root canals. Osteomyelitis is readily controlled and eliminated with ozone therapy. Urinary Bladder Insufflation The empty urinary bladder is filled with 37 gamma ozone over a period of 1-2 minutes. The ozone is retained for twenty minutes. Cervical, Thoracic, and Lumbar disc protrusions The “Discosan” method refers to a mode of treatment of herniated discs developed by an Italian orthopedic surgeon in 1984. He has since treated more than 6000 cases, with a 95% success rate. Chronic and acute disc problems are treated in the same way injecting about 3-5 cc’s of 37 gamma ozone via a 25 gauge 1 or 1 ½ inch needle in dogs. Inject the areas just lateral to the posterior edge of spinous processes of the disc space involved, the one anterior and the one posterior to it. Aim for and try to touch the bone of the articular facets of the vertebrae mentioned above. I also inject the interspinous spaces. Treatments are repeated twice to three times weekly until resolution, which will be 2 weeks to 2 months. As an alternative, injections can also be done into the paravertebral muscles at the level of the disc problem. If one has access to imaging equipment for needle placement and ozone injection directly into the disc, resolution of the problem is much accelerated. Go lightly on the local anaesthetics if you precede the ozone injections with local anaesthetics. Too large a quantity of local anaesthesia in the region of the spinal foraminae can lead to temporary or pseudo paralysis. Plate above shows disc protrusion: Plate below after 12 O3 treatments Tumours Tumour cells have a high intolerance to peroxides. These inhibit tumour growth by about 40-60% although do not ultimately seem to be curative. Ozone can be injected directly into the tumours but works just as well by injecting around the tumour. I use 37 gamma ozone. V Conditions for Which Ozone Has Been Used and Case Histories The literature is filled with treatments for so many common and many not so common problems, that I will simply list some of these (in addition to those already mentioned) and suggest that the bibliography or the reader’s imagination be consulted for specific treatment protocols. Coronary artery disease, atherosclerosis, angina, Reynard’s disease, Buergers disease, microvascular disease such as those associated with diabetes, gangrene, burns(chemical and thermal), intermittent claudication, macular degeneration, retinitis pigmentosa, chronic infections including herpes I and II, hepatitis B and C, Epstein Barr, Cytomegalovirus, HIV, mycoplasma, TB, cytomegalovirus, Lymes Disease, mycoses, Giardiasis, non healing wounds, osteomyelitis, cystitis, proctitis, dental and gum disease, tonsillitis, osteoarthritis, hypercholesterolemia, ischemic cerebrovascular disease, an adjunct to cancer treatment, antiaging/cerebral atrophy, gynaecological disease especially if infectious, osteoporosis, Parkinson’s disease, rheumatoid arthritis, peritonitis, silicon induced immune dysfunction, snakebite, chronic fatigue syndrome, fibromyalgia, enhancing brain function and athletic performance. VI Summary Medical ozone is an effective and safe treatment modality when used properly. The only way one can get into trouble is by administering the gas directly intravenously. Never use room air, only pure oxygen, to generate medical ozone. Room air will generate highly toxic nitrous and nitric oxides. The only known contraindications in medical syndromes are uncontrolled hyperthyroidism, and fauvism (deficient G-6-PD enzyme, the oxidant protection system of red blood cells), thrombocytopenia, and serious cardiovascular instability. We always, in addition, like so many other treatment modalities, list pregnancy under this heading, although personal communications suggest an enhancement of foetal development and birth processes by the use of ozone. Always use an ozone generator from a reputable company. No homemade versions please. The machine should be able to be calibrated and its ozone output periodically checked for reliability. Use concentrations of 80 gamma for disinfection only once or twice for direct introduction into tissues for disinfection purposes. This concentration inhibits tissue regeneration. Then use lower concentrations of around 37 gamma or less to effect tissue healing. This concentration will also be effective in disinfecting tissue. Use ozone in any and all disease conditions to enhance whatever modalities you are already using. “Imagination is more important than knowledge.” Albert Einstein. Bibliography 1. Flood Your Body With Oxygen by Ed McCabe, Energy Publications 6th edition, 2003 2. The Use of Ozone in Medicine by R. Viebahn-Haensler, Karl F Haug, publisher, 1999 3. Oxygen-Ozone Therapy, a Critical Evaluation by Dr Velio Bocci, Kluwer Academic Publishers, 2002 4. Oxygen Healing Therapies by Nathaniel Altman, Healing Arts Press, 1998 5. Second International Symposium on Ozone Applications Abstracts, 1997, Havana, Cuba 6. Principles of Medical Biochemistry by Meisenberg and Simmons, Mosby Publications, 1998 7. The Extraordinary Chemistry of Ordinary Things by Snyder, John Wiley and Sons Publishers, 2003 8. Fundamentals of Organic and Biological Chemistry by McMurray and Castellion, Prentice Hall Publishers, 1999 9. Textbook of Medical Physiology by Guyton and Hall, W.B. Saunders Publishers, 1996