Ouabain – the optimal solution for the problem of myocardial infarction
(Extracts from the book “Ouabain – the possible victory over the myocardial infarction” by Rolf-Jürgen Petry*)
One of the most necessary things in the contemporary medicine is to call attention to a topic that seems to be unbelievable at first sight: Ouabain (in german: g-Strophanthin), an extraction of an african plant called „strophanthus gratus“, which since 1991 is discovered as an endogenous substance – a new hormone-, prevents angina pectoris and myocardial infarction by nearly 100 percent without side effects. There is an overabundance of studies and documented experiences, so that its effects are quite obvious, even if the great clinical double-blind study is missing. But there is a mighty inscrutable opposition against the therapy with orally administered ouabain. There are two wrong tenets creating an impermeable wall:
1) Ouabain is like digitalis classified as a heart glycoside, with the indications „heart insufficiency“ and „arrhythmia“. Because digitalis has negative effects in angina pectoris and myocardial infarction, and „the story goes“ that all glycosides act similarly, the outstanding therapeutical results of ouabain don´t attract any attention at all in the medical establishment.
2) In the textbooks is written that ouabain has a very bad oral absorption – but there are over 20 studies which prove the contrary.
The worldwide best results
The best example for the indeed excellent therapeutic results of oral ouabain in angina pectoris and myocardial infarction is Prof.R.Dohrmann from Berlin (West), who has been the leader of a public hospital, starting 1975 with this therapy. In 1984 Dohrmann & Dohrmann published a study (1) dealing with oral ouabain therapy in unstable angina pectoris. 148 patients with severe stenosis visable in coronary angiography, who received for years all the medicaments modern medicine offers and who are dissatisfied because of continous heart attacks and in part unpleasant side effects, have been switched over (with their agreement after an information discourse) to the therapy with oral ouabain from one day to the other, i.e. the other medicaments including the ß-blockers (!) were discontinued immediately. From these 148 patients 122 were free from angina pectoris after one week, and after two weeks this success could be seen with 146 patients. They were also free from the side effects of the former medication. The other two patients had to stop the therapy because of some irritation of the digestion tract, the only harmless side effect which sometimes occures. (Perhaps a conversion to natural food could help in these cases.) The capsula which is dissolved in the small intestine is sufficient in most cases, and when in spite of this prophylaxis there is a heart attack, the capsula for lingual absorption surely helps in 5-10 minutes in almost every case. With this method every patient can help himself even in the case of acute myoardial infarction, before the ambulance can be present.
By the way it is not a necessary condition to discontinue the former medication: there have never been any interactions between oral ouabain and any other medicine, even not with digitalis, on the contrary the experience shows that oral ouabain reduces the side effects of digitalis, when this drug is necessary because of tachycardia.
The study of Dohrmann et al. of 1977 (2) deals with sublingually applied ouabain to all patients coming to the hospital with severe heart attacks, acute myocardial infarction (AMI) or suspected AMI. In 170 of 264 cases (= 64 %) the attack was totally stopped within 5-10 minutes, in the rest there has just been an AMI in a relatively late phase in 55 cases, when there is no success to be expected any more, so that only in 15 % of the patients with A.p. (but without AMI) there was no positive result with the first application of ouabain. The above mentioned study (1) shows that the optimal success is reached only within some days.
In the therapy of AMI Prof. Dohrmann introduced a new therapy (3) with i.v. cortison to stabilize the lysosomal membranes and i.v. k-strophanthine with great success, although the optimal time for applying ouabain or k-strophanthine in the first minutes of AMI had often just passed by when the patients were reaching the hospital. The quota of nonsurvivors (30 days) after myocardial infarction was previously very high (38 %) because there have been much more elderly people than in (the rest of) Germany. With this therapy he reached the worldwide best rate of survival of that time (in the first year (1977) 17 % nonsurvivors, and 1987, after 10 years, 15 % with experiences with over 1000 patients). A multicenter study of northern Germany reported a quota of 26 % mortality in a comparable period (3 a). Prof. Dohrmann was outnumbered only by Prof.DeMesquita from Sao Paolo (4) who used ouabain i.v. (9%).
Another example is a coal mine in Gelsenkirchen/Germany (5) where the average number of workers dying because of AMI in the mine under the surface of the earth was 3 every year; the way to the doctor lasted more than half an hour. After the doctor of the mine in 1974 began with oral ouabain therapy directly in the mine, the mortality concearning AMI was reduced to zero in the following 10 years.
In 1984, the small firm "Herbert Pharma" (the former producer of Strodival® – the only available ouabain medicament nowadays - in Wiesbaden / Germany) had made an inquiry to 3650 doctors with respective experiences (6). Ca. 98,5 % answers were very positive, and 1,5 % were positive with some limitation. Reading the released extract, the answeres of 300 physicians, published with full adress, is really convincing, very often they say: "excellently effective", "no side effects", "better than the rest", "I don't see deadly myocardial infarctions any more" and so on... (There wasn't enough money to corrupt such a great number of physicians to make such definite statements. The author talked to some of them, so that it wasn't a faked inventory)
The author could motivate some physicians to use ouabain. Their reports of a good therapeutical success are a good current authentication of the findings in the literature. The anthroposophic “Ita Wegman Klinik” in Switzerland are using ouabain since 2002 with the expected success. There are still about 3000 physicians in Germany who are using oral administered ouabain.
Ouabain and Digitalis behave oppositely at the cellular level
The commonly accepted receptor for heart glycosides, i.e. ouabain and digitalis and some other substances, is the sodium pump, which is present in the wall of every cell in a great number and which is pumping Natrium out of the cell and Kalium into it. This is very important for many fundamental functions of the cell.
In all textbooks and articles there is written that heart glycosides are inhibitors of the sodium pump. Ouabain is extensively used in many scientific experiments to block the sodium pump. But for all that, this is more false than true: The inhibition of the sodium pump occurs only with high concentrations of ouabain. On the contrary, the low concentrations of ouabain, which are present in the human body after taking the medicine or naturally because of the endogenous nature of ouabain, have the opposite effect. There are over 50 unnoticed and unrefuted studies, that report of the stimulation of the sodium pump by low doses of ouabain. The last one is Gao et al. 2002 from the University of New York (7). The result is a reduction of sodium and because sodium and calcium are associated (sodium-calcium-exchanger), also a reduction of calcium intracellularly. For digitalis the data is poor, but it seems to be that digitalis is not able to stimulate the sodium pump. This is the explanation for the differences between ouabain and digitalis preparations seen in many pharmaco-dynamical studies and especially seen in the therapeutical results.
Two study groups have detected an new receptor for heart glycosides in the inside of the cell, at the sarcoplasmic reticulum, the calcium store of the cell (8-9). The effect is a release of calcium. Ouabain acts tenfold weaker than Digoxin at this new intracellular receptor. Furthermore Santana et al. in 1998 (10) could show, that 0,1 nanoMol of digoxin, a concentration below those that are found in the human blood after digoxin medication, have the halfmaximal effect of opening the sodium channels for calcium, letting in 30 percent of the total calcium influx, whereas ouabain needs nearly the hundredfold concentration to achieve this effect. These differences between the actions of ouabain and digoxin are a good additional explanation for the different therapeutical effect of ouabain and digitalis in angina pectoris and heart infarction.
The fact that the activity of the sodium pump of heart cells in ischemia is diminished, and all scientists agree that the sodium pump plays the key role in the fate of these cells in this situation, is the background for the undoubtly excellent, unparalleled and solidly documented therapeutical effect of orally administered ouabain in angina pectoris and myocardial infarction.
Ouabain affects several components
Because the sodium pump is present in every cell, ouabain can influence not only the heart muscle cells. Because the cells exchange a part of their sodium for calcium, ouabain acts on the whole like a calcium antagonist. In addition ouabain combines the qualities of a whole train of medicaments.
The nerve cells as well have sodium pumps, they are even the cells with the highest frequency. Sharma et al. in 1980 saw a reduced output of norepinephrine in nerve terminals with low doses of ouabain, no change with intermediate concentrations and the normally published increase with high concentrations of ouabain (11). Gutman andBoonyaviroj 1977 (12) report that only low doses of ouabain are reducing the output of epinephrine and norepinephrine in the adrenal glands. So the medicament ouabain lowers the level of stress-hormones in the whole body and especially in the myocardium and acts also in the field of a beta-blocker.
Ouabain is enhancing the blood flow in the myocardium by action on the blood vessels and on the red blood cells. Manfred von Ardenne, the great scientist of the German Democratic Republic, made many investigations dealing with ouabain, for example in 1991 a scintigraphy with 99technetium showing a marked increase in myocardial blood flow by orally administered ouabain in patients with angina pectoris (13). This was confirmed by the findings of Vatner & Baig 1978 (Harvard) with ouabain i.v. in an animal experiment with dogs (14). Von Ardenne wrote one of the very few articles in English language about the therapy with orally administered ouabain (15).
Ouabain is also lowering the blood pressure – but only in the case of hypertension. A good example for the effect of low doses of ouabain on vascular smooth muscle is a study of Branco and Osswald from 1986 (16), where the authors report of the different actions of three different concentrations of ouabain on dog blood vessels. The two high concentrations caused a constriction (release of norepinephrine, a stress-hormone), but the low concentration had the contrary effect, as it would be expected from the studies of DeMots et al.1978 (17) and Marjorie et al. 1997(18). DeMots et al. 1978 (17) gave the same doses of ouabain i.v. to patients with different velocities. As expected, only the slow injection of ouabain caused a reduction of blood pressure and lactate levels in the heart.
Particularly important is the effect of ouabain on the red blood cells. Their diameter (8 micrometers) is bigger than the diameter of the capillaries, which they must pass (3 micrometers). To manage this, the erythrocytes have to make themselves very thin and long, really like a submarine. But because the acid and the free radicals generated in ischemia or even by an overactivity of the sympathetic nervous system (stress hormones) reduce the activity of the sodium pump of the erythrocytes, too, they become full with sodium and therefore full with water and tight and unflexible. Low concentrations of ouabain are able to stimulate the sodium pump of the erythrocytes. Prof.Lohmann (Giessen/Germany) in 1986 found a marked improved flexibility of erythrocytes even at low pH (19). So they get slim enough to pass through the capillaries again. Here Ouabain acts principally like an AAS preparation, like Aspirin®. Prof.E.Ernst and Dr.T.Saradeth 1991 (20) from Vienna had made a randomized, double-blind and placebo-controlled crossover-study with oral ouabain and found significant beneficial effects regarding the erythrocytes and hemodynamic parameters, for example a reduced rise of diastolic blood pressure in exercise.
Otherwise the situation could get very harmful. Because of the reduced flexibility of the red blood cells, the bloodflow is reduced and the acid accumulates. That will make the erythrocytes even more immobile and so on – a real vicious circle, that can produce the death of single heart muscle cells or even of bigger regions. This is a widely unnoticed mechanism of how a myocardial infarction could be generated. The reduction of the discussion on the formation of a coronary thrombus is not useful, because there are many studies that report of a low frequency of coronary thrombosis and in addition the thrombosis is time-dependent. The longer the period between myocardial infarction and death of the patient, the bigger is the frequency of coronary thrombosis. The well-known Swedish cardiologist Erhardt (et al. 1973 and 1976) made the final prove: He injected a portion of radiactive labeled fibrinogen into patients after a myocardial infarction. Fibrinogen builds up the thrombus and after this formation there is no exchange of fibrinogen any more. When a patient had died and a thrombus was found, in every case (!) the radioactivity was present in the whole thrombus, even in the middle section (21-22). This implies that the thrombus was not the cause, but the consequence of the myocardial infarction. The fact, that there is a tailback of blood in the coronary system and that in the situation of a myocardial infarction the heart cannot build up the normal pressure from outside into the coronary system, facilitates the formation of a coronary thrombosis at a point of a coronary artery which is narrowed formerly. So the action of ouabain on the red blood cells is very important.
In the last years the theory of the vulnerable coronary plaques has become more and more important. In the study of Matsumori et al 1997 (23) ouabain caused the quadruplication of survival in rats with sepsis because of a suppression of cytokine production ( IL-6 and TNF-alpha). Perhaps ouabain could show this effect also in the heart and coronary system and reduce the inflammatory process in the instable coronary plaques – this perhaps is another explanation for the beneficial therapeutical effect of low doses of ouabain.
Generally speaking, ouabain acts like a nitro-preparation:
There is a randomized, placebo-controlled double-blind study - Salz & Schneider of 1985 (24) in seven doctor´s surgeries which shows an excellent and highly significant result. The classical double-blind experiment of Kubicek and Reisner of 1973 (25) with angina pectoris-patients under hypoxia showed in 19 of 22 patients a marked improvement of the electrocardiogram (S-T-alterations) - in 7 cases a total normalization - after oral ouabain application in comparison to a control group, and the result of subjective state of health is as follows: control: 18 patients with pain or giddiness and only 4 without trouble. After oral ouabain: Only 4 patients with pain or giddiness and 18 patients are without trouble (!). A placebo showed no effect. Digitalis (several drugs in differentiated doses) had a negative effect, so that some experiments had to stop before the regular end. (Reference unfortunately only in German) Also Sharma et al. 1972 (26) had similar good results with i.v. ouabain. This is the corroboration of the therapeutical results reported by Prof. Dohrmann and others, see above.
Prof. Belz et al 1984 (27) made a placebo-controlled double-blind crossover-study, which shows that orally administered ouabain has a constant and significant (in part highly significant) effect on the heart contractility of healthy volunteers that is different from the effect of ouabain i.v. and similar to that of nitroglycerine. This finding was confirmed by a study of Prof. Dohrmann & Schlief-Pflug in 1986 (28) who investigated patients with severe CHD and instable angina pectoris.
As we have seen, ouabain combines the actions of several medicaments without their side effects and is the perfect pharmacological solution in the case of angina pectoris and myocardial infarction.
What is the effect of low concentrations of ouabain in ischemia/reperfusion injury? I never have seen a study in this direction at all. I think such an investigation could be a breakthrough ! Gousious et al. in 1967 made a study (29) which investigates the influence of ouabain in the isolated heart without ischemia: there was an increase in fatty acid oxidation in absence of increased uptake. The study of Horackova and Mullen in 1988 shows a reduction of the Ca++ content of isolated cardiomyocytes with low doses of ouabain, unchanged results with intermediate and the normally published rise with high concentrations of ouabain (30).
Ouabain as a possible universal remedy
There are 30 diseases other than angina pectoris, myocardial infarction and heart failure, for example diabetes, cancer, multiple sclerosis, Morbus Parkinson and Alzheimer, seizure disorder, schizophrenia, obesity, inflammable intestinal diseases, arthritis, allergies, toxications,..., in which the activity of the sodium pump of the regarding tissues or of the red or white blood cells is lowered. In this cases non-parenteral ouabain hypothetically could have a positive influence. There are no studies regarding the effect of ouabain in this diseases up to now. The diseases in which a therapeutic effect of ouabain is documented are cerebral ischemia, asthma bronchiale and endogenous depression (31-33).
The false dogma of the bad absorption of oral ouabain
The opinion that ouabain is very poorly absorbed when enteral administered, is not valid. Marzo et al. in 1974 (34) could demonstrate, that radioactively labeled ouabain (3H-ouabain) was absorbed at a rate of 36 % within 5 hours in guinea-pigs. Greenberger et al. in 1969 (35) found in the intestine of guinea-pigs for 3H-ouabain a mucosal tranfer of 19 % after only 30 minutes, more than 3H-digoxin (15 %). Forth et al. (36) reported of an enteral absorption of 3H-ouabain after only 1 hour at a rate of 24 % and 48 % in rats and guinea-pigs, respectively. There are some other examples (37-43): Kitano et al. in 1998 (44) refer of a high absorption of orally administered ouabain to rats, comparable with that of digoxin.The last study to mention is Leuschner & Winkler in 2001, who found 50 % of the orally administered 3H-ouabain in the organs of guinea pigs (45).
Lauterbach suggested that there is an active transport process for polar cardiac glycosides like ouabain through the intestinal cells (46-47). As a parallel there is an uptake process per endocytosis into the intracellular compartments of the myocardium (48).
There are high and non fluctuating blood levels of ouabain in humans in the studies of Erdle et al. in 1979 (49) and Marchetti et al. in 1972 (50) using orally administered 3H-ouabain, which astonishingly are not mentioned in the "Handbook of Experimental Pharmacology" (51). Here only the third respective study of Lahrtz et al. in 1968 (52) is mentioned, in which 1) too little of ouabain was given (0,04 mg; a normal therapeutic dose is 3-12 mg) and 2) indeed there was given too little of radioactivity, even below the detection limit, so that a positive result was impossible even if there had been an i.v. application. However, also the effects of orally administered ouabain on human haemodynamics support the finding of a high and linear, not uncertain absorption (Piscitello &b Maggi in 1973) (53). Interesting are also the studies of Belz et al. in 1984 and Dohrmann at al. in 1986 (27, 28).
Investigations with the RIA-method show much smaller amounts of ouabain-immunoreactivity in human blood after oral application, but also here is visible that there is no uncertain absorption, because the fluctuation of perlingual ouabain blood levels is less than the fluctuation after i.v.application (54-55), see below.
The fact that in the case of heart infarction there are no high levels of ouabin necessary like in the case of heart insufficiency, is unknown. Prof.Bereiter-Hahn (Frankfurt) in 1991 could show that even a concentration of 10(-13) M (= 60 quadrillionth gram in one millilitre) of ouabain has a reproducible effect on cardiomyocytes regarding the oxygen metabolism, in some cases even a concentration of 10(-15) did so (56). Another study (57) of the same group shows that 10(-10) M ouabain increases markedly the fatty acid oxydation of cardiomyocytes (but not the oxydation of other substrates), which is markedly diminished in ischemia.
Only a hair raising inconsistancy or a prearranged deception ?
The often published statement of the uncertain enteral absorption of ouabain has its only root in a single examination of another ouabain preparation called Purostrophan ®, which was available in the 1970ies and showed indeed some fluctuation of the results concerning the blood and urine levels of ouabain. Beside the fact, that this fluctuation wasn´t bigger than that of the commonly used Digitalis medicaments, I discovered, that the real examination of oral Purostrophan wasn't made in the oftenly cited study (54) of Prof. Greeff et al. in 1974, the accepted authority at that time, but one year before in a dissertation of his institute (58). The peculiarity of this dissertation is, that the examination of Purostrophan® has been made with two different groups of patients: one group took ouabain before and the other group took ouabain after the breakfast. In the text of the dissertation the expected result is written: The group who took the medicine before the breakfast had absorbed more ouabain than the other group. Already in the dissertation the different results were summarized to one diagramm and then were repeated by Prof. Greeff in his study (54) and other articles without citation, so that the origin remained hidden. This is the origin of the intensively published statement of an uncertain absorption of ouabain. This nonscientific results are published in the same study that reports of the lowly enteral absorption of ouabain and influenced the majority of the physicians not to prescribe ouabain to their patients.
The detection of ouabain as a new hormone and the birth of a new false dogma
Since 1991 ouabain is identified as an endogenous compound, produced by the adrenal glands and / or by the brain (hypothalamus). By the way, the possibility that ouabain is taken up with the food cannot be excluded – this would be another proof for the good absorption of ouabain. Unfortunately here you can observe the birth of a new false tenet: the role of endogenous ouabain as the cause of hypertension, which is based on contradictory studies with rats. The studies with other animals and one double blind clinical study are reporting of an unchanged or even lowered blood pressure, as do other studies and reports. For example, Tamura et al. in 2000 (59) report that a synthetic diet completely without heart glycosides causes hypertension in rats, which is prevented by orally administered ouabain in low dosage.
One of the studies, which deals with ouabain as the cause of essential hypertension, contains a surprising hint for the beneficial therapeutic effects of ouabain: Yuan et al. 1993 (60).. The rats with ouabain showed no cardiac hypertrophy, but the rats in the control group did so. Yuan et al. p.186: "Ouabain actually may be cardioprotective." The most important sentence of the whole study ! There are older studies who also report of the finding of the prevention of the hypertrophy of the heart and adrenals (61-62).
The solution of the problem is not wanted
Unfortunately there has been a systematic opposition against the excellent therapy with oral ouabain in angina pectoris and myocardial infarction, a German "speciality", so that the very many published convincing proves were not proclaimed adequately. This exasperated controversity reaches back to ca. 1950, when some of the German universities supported this therapy with which you see results which are unparalleled by any other, even modern medication. From 1905 until the 1950ies ouabain i.v. was the official therapy in heart insuffiency and also partially in angina pectoris and myocardial infarction. Especially in the 19seventies and 19eighties an International Society for Infarction Control (= "Internationale Gesellschaft für Infarktbekämpfung") with many supporting professors (Schaefer/Heidelberg, Baroldi/Milano...) strived for acknowledgement of the respective facts, but the "suppression fraction" of the medical establishment was too strong – in that time Prof. Gotthard Schettler was the main opposer. Prof. Erdmannn, director of the university hospital of Cologne / Germany and scientist with the main focus heart glycosides, was / is(?) the one who fighted against both the ouabain therapy and the stimulation of the sodium pump by low doses of ouabain. The attacks against ouabain were always unsubstancial and truthless, in part they were contradictory to the own statements made elsewhere.
The scepticism of many doctors in testing a substance which is classified as a cardiac glycoside, in angina pectoris, especially when in all textbooks is written that there is 0 % or 1-2 % absorption, is huge. There is a doctor, who has seen the excellent success in every of his 120 Angina pectoris-patients, but his collegues are laughing and even don't want to hear his story to the end. (I hope you are still reading...) There are doctors who have Strodival® in their drawer, and in case of emergency (severe angina attack, suspected AMI) they quickly applicate the capsula, but they don't inform the hospital, what they have done, because they fear to make themselves ridiculous. A real tragical story...
It is an urgent challenge to save the real possibility to solve one of the biggest medical problems (really: Oubain could be in Coronary Heart Disease something like insulin is in Diabetes.) and to preserve a blessed medicine that helps so many patients. But there is an acute danger that oral ouabain could die, especially after an imminent change in the respective law, so that the sick-funds don't pay any more for it. Even more grave: it is expected, that there is no prolongation of the licence for orally administered ouabain, because the big clinical double-blind study is missing, as it would cost about 10-15 millions of Euro, much more than the producer company could pay. Even a big multinational company would not pay this sum for a substance without a protection by patent. The orally ouabain therapy may die in 2 years. A real tragedy...
A special characteristic is the fact that in 1996 the small producer “Herbert Pharma” in Wiesbaden/ Germany was adopted by “BRAHMS Arzneimittel GmbH” in Wiesbaden (the new name was “Herbert Arzneimittel GmbH”). The director of the mother company – “BRAHMS AG” in Henningsdorf (Berlin) is the President of the German Federal Association of Pharmaceutical Industry, Dr. Bernd Wegener. The new producer is noticeable inactive ... . In 2003 “Herbert” was selled by “BRAHMS” to “MEDA”, a Swedish combine.
Without doubt ouabain (g-strophanthin) could be the solution of the problem cardiac infarction (“Killer No. 1”) to a large extent and especially the therapy with orally administered ouabain and the knowledge about this drug has to be brought forward because of medical, ethical and economic aspects.
* About the author
After Rolf-Jürgen Petry had finished his schooling as an alternative practitioner in 1997, he became a permanent visitor of the medical libraries, where he had copied about 20.000 pages in the last years about ouabain and myocardial infarction. He has read the original studies in a very accurate form and has found that the orthodox positions, with which ouabain is rejected, exhibit serious faults. It's really a severe miscarriage of medical justice, as you could see with the proofs above.
He has written the first extensive and detailed book on this theme with 1380 references and the preface of Prof. Hans Schaefer from Heidelberg, who was world-famous for some decades. (Rolf-Jürgen Petry: Strophanthin – der mögliche Sieg über den Herzinfarkt. (Ouabain – the possible victory over the myocardial infarction), 286 pages,21,90 € (Verlag Florilegium 2003, ISBN 3-00-010149-7), Pf 1305, D 27442 Gnarrenburg, Germany, Tel. 0049 – 4763 – 1092, Fax 0049 – 1212 – 55 14 09 321, e-mail: strophanthin@web.de
The book is on a high scientific level, but at the same time the author had taken great care that it remains understandable even for a person without previous medical knowledge. This book is available only in German language until now.
References:
1) in german: R.E.Dohrmann & M.Dohrmann: Neuere Therapie der instabilen Angina pectoris bei koronarer Herzerkrankung, Erfahrungsheilkunde - acta medica empirica 33: 183-190, 1984
2) in german: R.E.Dohrmann; H.D.Janisch & M.Kessel: Klinisch-poliklinische Studie über die Wirksamkeit von g-Strophanthin bei Angina pectoris und Myokardinfarkt, Cardiol Bull (Cardiologisches Bulletin) 14/15: 183-187, 1977
3) summary in english: R.E.Dohrmann & R.F.Heller: Therapeutische Ergebnisse bei akutem Myokardinfarkt unter Anwendung hoch-dosierter Steroidgaben und fluiditätsbeeinflussender Pharmaka - Ergebnisse einer 10-Jahres-Studie, Cardiol Bull 24: 17, 1987
3 a) H.J.Avenarius, H.Poliwoda & B.Schneider: Unersuchungen zum klinischen Verlauf des akuten Myokardinfarkts. Med Klin 72: 459-464, 1977
4) Prof. Quantiliano de Mesquita, Professor Honorario de Faculdade de Medicina de Universidade Federal de Paraiba. Chefo do Instituto de Angio Cardiologia de Hospital Matarazzo e Cas de Saude Matarazzo Sao Paulo: Teoria miogenico do enfarte miocardio. Verlag: Gemini, Sao Paulo (Brasilien), 1979, in Rundbrief 42 der Int.Gesellschaft für Infarktbekämpfung, Febr.1980 (später umbenannt in Gesellschaft für Infarktbekämpfung, weitere Umbenennung in Gesellschaft für Infarktverhütung. Sitz: Schorndorf-Haubersbronn, ausleihbar in Bilbliotheken (evtl. Fernleihe)
5) in german: H.Brembach: Infarktvorbeugung in der Arbeitsmedizin, notabene medici 7: 613-616, 1984
6) in german: Eine Dokumentation ambulanzkardiologischer Therapie-Ergebnisse nach Anwendung oralen g-Strophanthins, Herbert Pharma GmbH, Wiesbaden, 1984
7) Gao et al. (New York): Isoform-specific stimulation of cardiac Na/K pumps by nanomolar concentrations of glycosides. J Gen Physiol 119(4): 297-312, 2002
8) Stephen J.McGarry & Alan J.Williams: Digoxin activates sarcoplasmatic reticulum Ca++-release channels: a possible role in cardiac inotropy. Br J Pharmacol 108: 1043-1050, 1993
9) Masako Fujino & Sumiko Fujino: An immunohistochemical study of the significance of a new 31,5 kD ouabainreceptor protein isolated from cat cardiac muscle. Jpn J Pharmacol 67: 125-135, 1995
10) L.F.Santana, A.M.Gomez & W.J.Lederer Ca++ flux through promiscuos cardiac Na+ channels: slip-mode conductance.Science 279: 1027-33, 1998
11) Virendra K.Sharma, Lorelle A.Pottick & Shailesh Banerjee (New York): Ouabain stimulation of noradrenaline transport in guinea pig heart. Nature 286: 817-819, 1980
12) Yehuda Gutman & Punya Boonyaviroj: Mechanism of inhibition of catecholamine release from adrenal medulla by diphenylhydantoin and by low concentration of ouabain (10 (-10) M). Naunyn-Schmiedebergs Arch Pharmacol 296: 293-296, 1977
13) M.v.Ardenne, W.-K. Mayer, J.Schmidt, G.Rostock & W.Mohnike (Dresden): Klinische Prüfung des perlingual applizierten g-Strophanthin-Präparats Strodival (R) spezial mit Hilfe der 99 mTc-Myospect-Herztomographie. Z Klin Med 46: 667-669, 1991
14) S.F.Vatner & H.Baig (Harvard): Comparison of the effects of ouabain and isoproterenol on ischemic myocardium of conscious dogs, Circulation, 58: 654, 1978
15) M.von Ardenne: Research on the mechanism of myocardial infarctions and on counteracting measures, a new galenic form of the fast acting g-strophanthin, Agressologie 19: 13-22, 1978
16) D.Branco & W.Osswald: Ouabain-induced efflux of catecholaminess and metabolites from blood vessels of normotensive and hypertensive dogs, in E.Erdmann, K.Greeff, J.C.Skou: Cardiac Glycosides 1785-1985, Steinkopff Verlag, Darmstadt, 1986
17) Henry DeMots, Shabudin H.Rahimtoola, John H.McAnulty, George A.Porter (Portland / USA): Effects of ouabain on coronary and systemic vascular resistance and myocardial oxygen consumption in patients without heart failure, Am J Cardiol 41: 88-93, 1978
18) H.J.Marjorie G.Nelissen-Vrancken, Ju-Feng Wang, Harry A.J.Struijker Boudier, Regien G.Schoemaker, Jos S.F.Smits: Ouabain improves cardiac functionin vivo in rats with heart failure after chronic but not acute treatment. Naunyn-Schmiedebergs Arch Pharmacol 356: 203-209, 1997
19) in german: W.Strobelt, U.Karsten, W.Lohmann (Giessen): Biophysikalische Untersuchungen an Erythrocyten mit äquivalenten Dosen von g-Strophantin perlingual und Digitoxin zur Frage der Flexibilität und Mikroperfusion, Rundbrief 68 (April 1986) der Internat. Gesellschaft für Infarktbekämpfung, Schorndorf
20) in german: E.Ernst & T.Saradeth (Vienna): Hämorheologische Effekte durch g-Strophanthin, Erfahrungsheilkunde 40: 775-776, 1991
21) L.R.Erhardt, G.Unge, G.Boman (Stockholm): Formation of coronary arterial thrombi in relation to onset of necrosis in acute myocardial infarction in man. Am Heart J 91: 592-598, 1976
22) L.R.Erhardt, T.Lundmann & H.Mellstedt (Stockholm): Incorporation of 125 I-labelled fibrinogen into coronary arterial thrombi in acute myocardial infarction in man. Lancet 1: 387-390, 1973
23) Akira Matsumori, Koh Ono, Ryosuke Nishio, Hiseki Igata, Tetsuo Shioi, Shigeo Matsui, Yutaka Furukawa, Atsushi Iwasaki, Yoshisuke Nose, Shigetake Sasayama (Kyoto / Japan): Modulation of cytokine production and protection against lethal endotoxemia by the cardiac glycoside ouabain. Circulation 96: 1501-6, 1997
24) in german: H.Salz & B.Schneider: Perlinguales g-Strophanthin bei stabiler Angina pectoris, Z Allg Med (Zeitschrift für Allgemeinmedizin) 61: 1223-1228, 1985
25) in german: F.Kubicek, Th.Reisner: Hypoxietoleranz bei koronarer Herzkrankheit unter der Einwirkung von Digoxin, ß-methyl-Digoxin und g-Strophanthin, Ther d.Gegenw (Therapie der Gegenwart) Heft 5 1973, S.747-768
26) B.Sharma, P.A.Majid, M.K.Meeran; W.Whitaker & S.H.Taylor (Leeds / GB): Clinical, electrocardiographic, and haemodynamic effects of digitalis (ouabain) in angina pectoris, Br Heart J 34: 631-637, 1972
27) G.G.Belz, J.Mathews, U.Sauer, H.Stern & B.Schneider (Wiesbaden /Germany): Pharmacodynamic effects of ouabain following single sublingual and intravenous doses in normal subjects. Eur J Clin Pharmacol 26: 287-292, 1984
28) summary in english: R.E.Dohrmann und E.Schlief-Pflug (Berlin): Echokardiographische Studie zum Wirkungsnachweis äquivalenter Dosierungen von Nitrolingual und Strodival spezial bei Patienten mit koronarer Herzkrankheit Cardiol.-Angiol Bull 23: 18-22, 1986
29) Aristides G.Gousios, James M.Felts, Richard J.Havel (San Francisco + Bethesda) 1967 Circ Res 21: 445-448, Effects of ouabain on force of contraction, oxygen consumption, and metabolism of free fatty acids in the perfused rabbit heart.Naunyn-Schmiedebergs Arch Pharmacol 356: 203-209, 1967
30) M.Horackova, S.Mullen (Halifax,Kanada): The dual effects of ouabain on 45Ca++ transport and contractility in adult rat ventricular myocytes. Pflügers Archiv 412: 277-284, 1988
31) summary in english: W.D.Heiss, Th.Reisner, H.Reisner, L.Havelec, F.Kubicek & K.Dietmann (Wien): Effect of ouabain on cerebral blood flow, Wiener klinische Wochenschrift 88: 171-174, 1976
32) Krishna P.Agrawal, Charles E.Reed, Robert E.Hyatt, Wayne E.Imber, Willane S.Krell: Airway responses to inhaled ouabain in subjects with and without asthma, Mayo Clin Proc 61: 778-784, 1986
33) in german: M.Michalik, R.Uebelhack, I.Grote, G.Ehle & K.Seidel: Das Verhalten vegetativer Parameter unter Anwendung von Ouabain (g-Strophanthin) bei endogen depressiven Patienten. Schweizer Archiv für Neurologie, Neurochirurgie und Psychiatrie 125: 163-178, 1979
34) A.Marzo, P.Ghirardi & G.Marchetti: The absorption, distribution and excretion of k-strophanthoside-3H in guinea-pigs afterparenteral administration, J Pharmacol Exp Ther 183: 185-193, 1974
35) Norton J.Greenberger, Richard P.MacDermott, James F.Martin & Saradindu Dutta (Chicago): Intestinal absorption os six tritium-labeled digitalis glycosides in rats and guinea pigs, J Pharmacol Exp Ther 167: 265-273
36) in german: W.Forth, E.Furukawa & W.Rummel: Comparative studies of the absorption and elimination of tritium-labelled cardiac glycosides, Naunyn-Schmiedebergs Arch Pharmak 263: 206-208, 1969
37) W.Forth & W.Rummel: Vergleichende Untersuchung der intestinalen Resorption von 3H-markierten Herzglykosiden in vitro und in vivo. Naunyn-Schmiedebergs Archiv 260: 112-114, 1968
38) W.Forth, E.Furukawa, W.Rummel & H.Andres: Intestinale Resorption von Herzglykosiden in vitro und in vivo. Naunyn-Schmiedebergs Arch Pharmak Exp Pathol 262: 53-72, 1969
39) W.Forth, E.Furukawa, W.Rummel & H.Andres: Die Bestimmung der intestinalen Resorption von Herzglykosiden durch Messung der 3H-markierten Glykoside im Portalvenenblut und in der Darmlymphe bei Katzen. Naunyn-Schmiedebergs Archiv 264 (1969) 406, 1969
40) K.Buchtela, K.Drexler, A.Fehringer, H.Hackl, M.Königstein & J.Schläger: Vergleichende Untersuchung über Resorption, Verteilung und Ausscheidung einiger herzwirksamer Glykoside im Tierversuch. Wien Z Inn Med 51: 227, 1970
41) H.Ohlmeier & A.Ruiz-Torres: Die Digitoxin- und g-Strophanthin-Resorption an der perfundierten Dünndarmschlinge der Ratte. Arzneim-Forsch 22 :1874, 1972
42) F.W.Hempelmann, N.Heinz & H.Flasch: Lipophilie und enterale Resorption bei Cardenoliden), Arzneimittelforschung / Drug Research 28: 2182, 1978
43) A.Garbe & H.Nowak: Zur Pharmakokinetik des Peruvosid. Arzneimittel-Forsch 18: 1597, 1968
44) Shoichi Kitano, Shigeto Morimoto, Akira Nishibe, Keisuke Fukuo, Atushi Hirotani, Takeshi Nakahashi, Osamu Yasuda & Toshio Ogihara: Exogenous Ouabain is accumulated in the adrenals and mimics the kinetics of endogenous digitalis-like-factor in rats. Hypertens Res 21: 47-56, 1998
45) J.Leuschner & A.Winkler (Hamburg): Toxicological studies with ouabain. Naunyn-Schmiedeberg´s Arch Pharmacol 363 (4) Suppl.: 139, abstract 544, 2001
46) in german, abstract in english: Fritz Lauterbach, Günther Vogel & Ingeborg Baumann: Die Abhängigkeit der enteralen Wirkungsquote kardiotoner Steroide von der angebotenen Dosis, Naunyn-Schmiedebergs Arch Pharmak exp Pathol 259: 248-259, 1968
47) Fritz Lauterbach in Kurt Greeff (ed.): "Handbook of Experimental Pharmacology", Vol. 56/II, 1981
48) Harol Nunez-Duran, Laura Riboni, Ernestina Ubaldo, Emilio Kabela, & Laura Barcenas-Ruiz: Ouabain uptake by endocytosis in isolated guinea pig atria. J Am Physiol 255: C479-C485, 1988
49) in german: H.P.Erdle, K.D.Schultz, E.Wetzel & F.Gross: Resorption und Ausscheidung von g-Strophanthin nach intravenöser und perlingualer Gabe, Dtsch Med Wschr. (Deutsche Medizinische Wochenschrift) 104: 976-979, 1979
50) G.V.Marchetti, A.Marzo, C.de Ponti, A.Scvalvini, L.Merlo & V.Noseda: Blood levels and tissue distribution of 3H-Ouabain administered per os, Arzneim Forsch (Drug Res) 21: 1399-1403, 1972
51) K.Greeff & K.E.Wirth: Pharmacokinetics of strophantus glykosides, in Kurt Greeff: Handbook of Experimental Pharmacology, Band 56 II : Cardiac Glykosides, S.56-85, Springer B-Hdlbg-N.Y., 1981
52) summary in english: H.Lahrtz, R.W.Sattler & P.A.van Zwieten: Über den Blutspiegel und die Ausscheidung radioaktiv markierter Herzglykoside nach deren intraduodenaler Applikation bei der Katze, Z ges exp Med (Zeitschrift für die gesamte experimentelle Medizin) 148: 210-222, 1968
53) F.Piscitello & G.C.Maggi: Effectiveness of orally administered g-Strophanthin on haemodynamics in cardiac patients, Arzneim.-Forsch (Drug Res) 23: 1546-1547, 1973
54) in german: K.Greeff, E.Köhler, H.Strobach, E.Verspohl: Zur Pharmakokinetik des g-Strophanthins, Verh Dtsch Ges Kreislaufforschg (Verhandlungen der Deutschen Gesellschaft für Kreislaufforschung) 40: 301-305, 1974
55) H.Strobach, K.E.Wirth & K.Rojsathaporn: absorption, metabolism and elimination of strophanthus glycosides in man, Naunyn-Schmiedebergs Arch Pharmacol 334: 496-500, 1986
56) M.Riehle, J.Bereiter-Hahn & B.Boller: Effects of ouabain and digitoxin on the respiration of chick embryo cardiomyocytes in culture, Arzneim-Forsch / Drug Res 41: 378-384, 1991
57) M.Riehle and J.Bereiter-Hahn: Ouabain and Digitoxin as modulators of chick embryo cardiomyocyte energy metabolism, Arzneim-Forsch 44: 943-947, 1994
58) in german: E.Verspohl: Entwicklung radioimmunologischer Methoden zur Bestimmung von Herzglykosiden des Digitoxigenins, g-Strophanthins und k-Strophantidins mit Untersuchungen zur Pharmakokinetik des Digitoxins und g-Strophanthins. Inaugural-Dissertation, Düsseldorf 1973
59) M.Tamura, H.Utsunomiya, M.Nakamura & E.J.Landon (Nashville / USA): Effect of dietary glycosides on blood pressure regulation in rats: Can J Physiol Pharmacol 78(7): 548-56, 2000
60) Christina M.Yuan, Paolo Manunta, John M.Hamlyn, Shanwan Chen, Erin Bohen, Jane Yeun, Francis J.Haddy & Motilal B.Pamnani (Bethesda, Washington, Baltimore / USA): Long-term ouabain administration produces hypertension in rats. Hypertension 22: 178-187, 1993
61) in german: E.Moskopf & H.Dietz: Experimentelle u. klinische Untersuchungen über eine zuverlässige orale Strophanthintherapie. Die Medizinische Welt 1955, p. 1375-77
62) in german: G.Kuschinsky: Die Verhütung von Erschöpfungszuständen des Herzens. Klin Wschr 24/25 (1947) 502-503
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