Positive Health Online

An Amazing and Shocking Story 

“Although one can harm or kill even a healthy man with injudicious use of digitalis, in the author's experience with acute myocardial infarction, complications (including the onset of ventricular tachycardia and the occurrence of sudden death) appeared as often in those patients who were not receiving digitalis as in those who were receiving it. In a series of 265 consecutive cases, his first admission mortality rate was 10 percent, compared with that of 16 percent in a similar series of 286 cases. This suggests that the use of digitalis was not strikingly harmful, and may well have been beneficial”, Ferdinand R Schemm, 

1950 [1]

The first therapeutic use of digitalis with beneficial effects for heart disease was described by William Withering in 1785. Withering did not understand how this drug acted on cardiac dropsy (edema due to congestive heart failure). However he was aware that digitalis exerted some action on the heart and that it retarded the pulse, for he wrote, “That it has a power over the motion of the heart, to a degree yet unobserved in any other medicine, and that this power may be converted to salutary ends.” [2]

It is important to note that during the 19th century the term congestive heart failure was used to designate other diseases of the heart and, in the beginning of the 20th century, digitalis was prescribed for the treatment of organic heart disease, including angina, During this time digitalis was extensively indicated in hypertension cases, especially associated with cardiac enlargement, to prevent heart failure. [3]

Digitalis Purpurea

Some praises for Digitalis:

“A God-given remedy”, 

Friedrich Ludwig Kreysig, Berlin. 1814 [4]

“The opium of the heart”, 

Jean Baptiste Bouillaud, Paris, 1841 [5]

In his classic paper about coronary thrombosis (thrombogenic) theory written in the early 20th century, Dr. James Bryan Herrick (1912), besides presenting his proposition of a pathophysiological triggering mechanism, wrote of his therapeutic experience using digitalis and strophanthin for angina pectoris and in the event of coronary thrombosis[6].  Herrick said:

“…If these cases are recognized, the importance of absolute rest in bed for several days is clear. It would seem to be far wiser to use Digitalis, Strophanthus or their congeners than to follow the routine practice of giving Nitroglycerin or allied drugs. The hope for the damaged Myocardium lies in the direction of securing a supply of blood through friendly neighbouring vessels, so as to restore so far as possible its functional integrity. Digitalis or Strophanthus, by increasing the force of the heart’s beat, would tend to help in this direction more than the Nitrites. The prejudice against Digitalis in cases in which the Myocardium is weak is only partially grounded in fact. Clinical experience shows this remedy to be of great value in Angina, and especially in cases of angina with low blood pressure, and these obstructive cases come under this head. The timely use of this remedy may occasionally in such cases save life. Quick results should also be sought by using it hypodermically or intravenously. Other quickly acting heart remedies would also be of service.”

Herrick’s priority in his treatment approach was to preserve the myocardium in the occurrence of coronary thrombosis. Undoubtedly Herrick was the first to raise the importance of coronary collateral circulation using the cardiotonic to restore the functional integrity of the myocardium. This clinical approach was largely ignored by his colleagues; perhaps it didn’t sound plausible, possibly due to the absence of experimental support. 

Or perhaps Withering was right in his despair:

 “I wish it was easy to write about Digitalis. I despair of pleasing myself or instructing others in a subject so difficult. It is much easier to write about a disease than a remedy. The former is in the hands of nature and a faithful observer with an eye to tolerable judgment cannot fail to delineate a likeness; the latter will ever be subject to the whims, the inaccuracies and the blunders of mankind.” William Withering, Letter, Sep 29, 1778.[7]

Regardless, the fact is that Herrick’s therapeutic approach isn’t taught at medical schools or discussed in scientific papers. As a result, most physicians remain in total medical ignorance about Herrick’s clinical practice in the treatment of angina and coronary thrombosis (acute myocardial infarction), also known under the general term ‘heart attack’. Herrick’s Thrombogenic Theory was adopted, but his therapeutic conduct was forgotten. This repeated omission over time has certainly contributed to the formation of the current dogma on how to deal with heart disease.

Louis Hamann in 1926 shared the same idea and enthusiasm of Herrick about the digitalis use in the treatment of coronary thrombosis. He said. "The patient should be promptly and fully digitalized. Not only is the digitalized heart better prepared to withstand the added burden of certain arrhythmias should they come on, but it is also stimulated to put forth its best efforts. How desirable the best efforts may be when a large area of heart muscle is infarcted, needs no further comment."[8]

Doctors in different times and countries have used digitalis or strophanthin in the treatment of acute myocardial infarction and angina. Some doctors also used digitalis or strophanthin as prevention therapy

Strophantus Gratus

Strophanthins are extracted from Strophanthus Gratus tree (g-strophanthin), Strophanthus Kombe tree (k-strophanthin) or the Acocanthera ouabaio tree (Ouabain – identical with g-strophanthin). These drugs were used originally by inhabitants from Africa as arrow poisons.  In the USA, due to a few unfavourable experiences during the early years of intravenous strophanthin administration attributable to individual therapeutic mistakes there was a general refusal by the American physicians to use intravenous strophanthin for routine treatment.[9]

Meanwhile Dr Ernst Edens from Germany, after using for 3 years strophanthin injections intravenously for angina and infarction, in over 100 patients, referred to it as a divine blessing, saying the strophanthin treatment is the safest treatment for the organic cause of angina pectoris and myocardial infarction. His idea was that the poor blood supply through the coronaries would be improved by the treatment with strophanthin. He stated that with this recognition nobody would have the right to use strophanthin only for scientific reasons and testing, giving preference to other remedies and thus losing precious time for cure. He also expressed the view that the time will come in which the omission of the use of strophanthin therapy would be seen as a professional malpractice. 

Edens, who was Professor at the University of Dusseldorf, presented his initial clinical experience with strophanthin during a medical congress in Wiesbaden held in 1931. On that occasion he stated that he had the myocardial infarction under control. However he was not apt to explain the exact strophanthin mechanisms in relation to the cardiac muscle, telling that he acted inside the principle: "Whether we understand it or not what happens here is that strophanthin works effectively and so we need to use it." Few of the doctors participating at the Wiesbaden Congress showed interest in the experiences from Edens regarding the use of strophanthin in the acute myocardial infarction. On the contrary, most of his medical colleagues reacted with hostility, trying to suppress his voice as if it was an intruder. The practical experience of Edens and his pupils H Zimmermann and Wagenfeld, in the treatment of angina and myocardial infarction, by intravenous strophanthin use, gained some followers.[9,10,11,12,13,14]

Berthold Kern, cardiologist from Stuttgart, Germany, based on his own theory that the low pH value found in the inner layers of the left ventricle would be the cause of infarction, prescribed oral (sublingual) g-strophanthin for the prevention of myocardial infarction. According to his theory the myocardial infarction occurs due to a formation of lactic acid in excess, destroying the cells and causing a chain reaction such as a fire in a forest which only strophanthin, for its acidity-lowering effect in the heart muscle, would be able to stop the infarction process. He adopted the view that the myocardial infarction was not caused by coronary thrombosis but by myocardial origin.

Berthold Kern prescribed as prophylaxis daily doses of sub-lingual g-strophanthin to 17,000 patients during the period from 1947 to 1971, resulting in a small number of infarctions (150 cases) and near zero deaths related to heart problems.[15,16,17] 

Berthold Kern and colleagues, defending the use of sub-lingual strophanthin for prevention of the myocardial infarction were literally executed in a symposium held in late 1971 in Heidelberg, at the Molkenkur restaurant. There they met large criticism by the orthodox medicine. The opposing doctors, who attended in considerable numbers to the event, accused their therapy on the grounds that the gastric absorption of strophanthin administered orally, was minimal and insufficient to achieve the desired effect. According to their opponents much larger doses would be needed and that could lead to poisoning. This medical meeting became known as the Heidelberg Tribunal with the attendance of the press, radio and television. Even today, the Heidelberg Tribunal is the starting point for frequently spread obscure conspiracy theories.[12,18,19,20]

After this time very few research, discussions as well as teachings and publications took place in academia about the use of strophanthin for prevention or to fight heart attacks. The use of strophanthin was banned and made taboo by the official medical practice.  However, the opponents of sublingual strophanthin-g were mistaken because it is also absorbed by the adrenal gland, among other findings, showing positive effects for the human body as demonstrated lately. These findings allowed new opportunities on the use of strophanthin for other medical conditions. 

Until some years ago about 5,000 doctors from Germany gave prescriptions for oral g-strophanthin to their patients. In a survey published during the eighties 3,645 German doctors made statements on the use of this medicine in their medical practices from 1976 to 1983. This survey showed that nearly 95% of them gave positive testimony, with no reservations. There was no negative feedback regarding the treatment with oral strophanthin-g, for the remainder of the doctors who participated in the survey.[21]

Dr Thomas Cowan, from San Francisco - California USA, is one of those physicians currently using Ouabain (g-strophanthin) for prevention and treatment of infarctions in their patients, with great success.[22] 

The Brazilian Dr Quintiliano H de Mesquita developed in 1972 the myogenic theory of myocardial infarction, where cardiotonics like digitalis and strophanthin are the fundamental and specific drugs for the coronary-myocardial disease, including acute myocardial syndromes.[23]

In his book, Myogenic Theory of Myocardial Infarction (1979), Dr Mesquita explained that the triggering cause represented by physical exertion or psycho-emotional stress increases the activity of the heart in the face of the fixed or deficient flow in the coronary blood supply, producing the regional ischemia. The lack of blood supply then leads to the loss of contractility within a few seconds, along with reduced ejection phase, increased volume and final diastolic pressure during the ischemia, along with an overload in contractility of normal regions of the heart. Each episode of myocardial ischemia by stress or emotion affects the cardiac muscle segment dependent on the affected coronary artery, compromising the myocardial structure. Over time the repeated ischemic manifestations in the same regions of the heart will cause pathological structural changes, different from the unaffected surrounding non-ischemic areas of normal structure.

He also stated in his book: “Thus, the coronary disease contributes to the deterioration of the ventricular segment, constituting areas of myocardial sclerosis or segmental myocardial disease, the possible future site of the myocardial infarction”. In his view, the anaerobic metabolism, with excessive lactate production, represents a step toward the myocardial infarction and necrosis in the particular region of the heart.[24]

Dr Mesquita, prescribed from period 1972-1979 strophanthin or digitalis, intravenously, in 1183 patients with acute myocardial infarction, registering an overall hospital mortality of 12%. In 126 cases of unstable angina, using intravenous strophanthin avoided the infarction and obtained a mortality of 0% during hospital stay.[25,26,27]

These patients were treated at the Cardiology Institute at Matarazzo Hospital, headed by Dr Mesquita. His Institute was a centre of medical excellence and school where many doctors came from all over the country for medical internship. The preference from Dr Mesquita was the use of intravenous strophanthin in patients with unstable angina and acute myocardial infarction. As I wrote in a recent article about his preference: “His many years of clinical experience led him to conclude that intravenous strophanthin (K or G) was the most reliable cardiotonic in all cases of acute myocardial infarction complicated by heart failure.”[28,29]

Rolf Dorhman from the Berliner Waldkrankenhauses in Berlin - Germany, achieved during 5 years similar results to the Brazilian professor applying the treatment with intravenous strophanthin to fight the acute myocardial infarction, according to a report by Dr Peter Schmidsberger at Bunte Magazine in 1980.[13, 30] 

Particularly interesting is that besides improving myocardial contractility the drugs Digitalis and Strophanthin have important properties under the view of his myogenic theory like sympatho-inhibitory response and potent inhibition over glycolysis, reducing lactate production.[31] 

In 1975 Dr Mesquita was awarded the Ernst Edens Traditionspreis by the International Society to Fight Infarction (Internationale Gesellschaft für Infarktbekämpfung), whose president at the time was Dr Berthold Kern.[32]

In the treatment of stable ischemic heart disease patients, with or without previous myocardial infarction, Dr Mesquita’s preference was the use of oral digitalis at low-dosages. During 28 years, using digoxin and other digitalis drugs, he achieved a total annual mortality rate of only 0.5% in patients without infarction (994 pts.) and 1.4% in cases with prior infarction (154 pts.).[33,34]

A study published in 1995, by Leor et al, has shown that one year mortality was significantly higher among patients treated with a full dose [19 of 112 (17%)] than patients treated with a low dose of digoxin [1 of 41 (2%)]. This is comparable to the remarkable results obtained since 1972 by Mesquita and colleagues in patients with previous infarction taking daily digitalis at low concentrations by the oral route.[35]

The myogenic theory and its consistent indication for the use of cardiotonics (digitalis, strophanthin, etc.) in the stable ischemic heart disease or in the treatment of acute myocardial infarction had a rather cold reception. There was a continued silence about the subject that lasts to this day. The skeptical medical elite acted with disinterest regarding the myogenic theory. Dr Mesquita never received external funds for his researches. Neither did he have any intention to give up from the pursuit of the medical truth, even if at his own expense. Most of his papers about the myogenic theory were rejected in the peer review process from medical journals. However, he never suffered direct attacks by his medical colleagues that recognized his great scientific status and integrity. They were quite satisfied and conveniently established with their apparently well-established theories and medicines. On the other hand, the public knowledge about the myogenic theory could jeopardize their economic and prestige achievements. So, the myogenic theory was transformed in a taboo inside the medical field. 

Dr Mesquita in the beginning of the forties, participated in the foundation of the Brazilian Cardiology Society being the first treasurer. When he died in October 2000 I paid a posthumous tribute to him which was published in January 2001 in the Brazilian Archives of Cardiology - journal of the Brazilian Cardiology Society. I said in my homage to him, about his many pioneering contributions to the cardiological science, among these: 1) The first case of ventricular aneurysmectomy surgery performed by Charles Bailey, in 1954; 2) The first case of right ventricular infarction with the diagnostic held in a live patient inside new electrocardiographic patterns contradicting Cavity Potential Theory of Q waves and confirming the Vectorial Theory of ECG, in 1960; 3) The Myogenic Theory of Myocardial Infarction, in 1972; 4) The confirmation of the Accelerated Conduction Theory from Myron Prinzmetal, 1999.[36]  

Intravenous strophanthin was withdrawn from the pharmaceutical arsenal in Brazil at the end of the seventies, maybe a retaliation from the ‘status quo’. Later both intravenous and oral (sublingual) strophanthins were withdrawn from the pharmaceutical arsenal in Germany, certainly due to the same reasons that occurred in Brazil.[17]  The difficulties to obtain strophanthin in Brazil led Dr Mesquita to the use of intravenous digitalis in patients having unstable angina or acute myocardial infarction, with good results for digitalis but not as good as strophanthin. 

Digoxin Removal from the Market: A Possible Scenario?

During the last year a scandalous situation occurred with the lack of digoxin pills from the main pharmacies and drugstores in Brazil, lasting about 4 months (From March until June 2015).[37]

The absence of digoxin during this period of time has obliged local physicians to change the prescriptions of patients with heart failure or with atrial fibrillation for drugs without the properties and effectiveness of digoxin. A well-known fact is that the digoxin removal may exacerbate the heart failure, putting the patients in risk of life.  Fortunately the judicial system in Brazil is working satisfactorily. The Prosecutor’s Office in their Extrajudicial Civil Division has intervened on the subject that resulted in the normalization of digoxin supply to the Brazilian market. The fact is that digoxin, as well as other drugs derived from digitalis (foxglove) were used for over 200 years in the treatment of heart failure. Digitalis has no patent and a very low cost for the patient. The digoxin therapy was also associated in studies with a significant cost reduction related to hospitalizations for heart failure. 

It is unclear if economic factors were the unique reason for the possible tentative withdrawal of digoxin from the market, not existing scientific justifications for what has happened in Brazil. It seems like an attempt to probe the terrain that, if successful, might lead the pharmaceutical companies to do the same in other countries (or in a global manner) during the next years.

Coincidently there was a recent study published in the European Heart Journal (May 4, 2015), largely promoted in medical news journals and in the media in general, saying that digoxin increases the risk of early death in patients with heart problems. This study, entitled Digoxin associated mortality: a systematic review and meta-analysis of the literature[38], is highly misleading because: 1) The authors presented in their study statistical numbers based on increased relative risk instead increased absolute risk, inflating in this way to 21% what in the real world  might be less than 1% increase in mortality, so scaring those people not familiarized with statistical formulas;  2) The demonstration from studies that low dose of digoxin (0.125 mg daily) is sufficient to achieve the serum digoxin concentration (SDC) currently recommended (0.5 to 0.9 ng/mL). Among the benefits of the low dose of digoxin are better hemodynamic effects and improvement of the neurohormonal profile - stress reduction. Obviously the current recommendation for SDC, that started in 2006, was not followed in many of the papers selected by the authors in the period studied (1993 – 2014);  3) The authors made a tremendous cherry picking to find what interested them to present (From a total of 1524 studies initially identified, only 19 matched their search criteria), discarding some important studies and information, not fitting with their direction;  4) Also, the authors didn’t take into consideration in their analysis that patients taking digoxin are usually older, with more severe pathologies and high mortality risk;  5) On the other hand, the authors focused too much in their opinions about the supposed potential mechanisms of digoxin-associated mortality increase, which do not occur with low dose of this drug.

The landmark study made by the Digitalis Investigation Group (DIG) trial from 1997 concluded that digoxin did not reduce overall mortality, but reduced the rate of hospitalization both overall and for worsening heart failure.[39] 

The evidence that the autonomic nervous system dysfunction plays an important role in the pathogenesis of atrial fibrillation was discussed in a recent review.[40]  It has been known for more than one hundred years that heart failure is also characterized by autonomic dysfunction with excessive sympathetic nervous system activity. The autonomic dysfunction may be improved through the use of digoxin at low dose by restoring the balance between the sympathetic nervous system and the parasympathetic nervous system activity.  

Apparently the paper published in the European Heart Journal wasn’t sponsored by the pharmaceutical industry. However, there are declared conflicts of interest from part of the authors, regarding their relationship with the pharmaceutical industry. Frankly this paper sounds like a libel in case of this supposed but rather possible campaign against digoxin. Incidentally, Dr Melissa Walton Shirley in an article entitled The Demonization of Digitalis: Plain Stupid, published in Medscape, talked about the pressure to doctors from the insurance companies that they stop patient's digitalis and replace it with other cardiac drugs. This represents an unethical and immoral request from those working with insurance companies.[41]

Groundless Concerns about the Use of Digitalis or Strophanthin  in Stable Ischemic Heart Disease or in Acute Myocardial Infarction

The concern that digitalis and strophanthin might have a detrimental effect on the recent infarcted myocardium, have arisen from observations made decades ago in animals, following coronary ligation, which have shown an increased incidence of ventricular arrhythmias and an extension of the area of infarction. 

However these results from experiments in animals have not to date been proved in humans. It should be taken into account that it takes hours and days for a thrombus to develop enough to block a heart artery. From the myogenic theory point of view, the thrombus formation is a consequence of the myocardial infarction, not its cause.

Discussing the use of digitalis in myocardial infarction Arthur Dodek said in 1974: “The appropriate use of this drug should be guided by sound scientific studies, not by unsupported opinions, speculations or clinical impressions.”[42]

The reading of the chapter “Cardiotonic in Acute Myocardial Infarction and Chronic Coronaropathy” is strongly recommended, translated to English from the book Myogenic Theory of Myocardial Infarction, 1979, with temporary free access.[43]

It contains the historical use of digitalis (digoxin, digitoxin) and strophanthin /ouabain (in the treatment of stable ischemic heart disease and acute myocardial syndromes. In this chapter was presented the view that there are no valid clinical studies proving that digitalis danger exists in human myocardial infarction. In a summary of his book Dr Mesquita, says:

“Papers on experimental pharmacological studies have been responsible for the absolute contraindication of cardiotonics for acute myocardial infarction, as a result of their possible damaging action, owing to the increase of contractility and of oxygen consumption under conditions of a smaller oxygen supply.

“Spreading such concepts generated a ban against cardiotonics on acute infarction cases. Nevertheless, clinical papers on the administration of cardiotonics in acute myocardial infarction, in spite of no experimental support, have been stimulating in their results, with absence of complications and a low mortality rate. These features oppose each other, but they are significant and sound, because the therapeutic results have consecrated these drugs and should awaken the researchers to them”.

References

1)     Schemm, F. R.: Digitalis in Cardiac Disease Without Congestive Heart Failure or Auricular Fibrillation, Postgrad. Med. 7:385 (June), 1950.

2)     William Withering, Cardiac Classics. The C.V. Mosby Company, 1941; St. Louis, USA 

3)     Drew Luten. The Clinical use of digitalis. Charles C Thomas, 1936.

4)     Willius FA and Dry TJ. A history of the heart and circulation, p. 114, W. B Saunders, 1948.

5)     Willius FA and Dry TJ. A history of the heart and circulation, p. 126, W. B Saunders, 1948.

6)     Herrick JB. Clinical features of sudden obstruction of the coronary arteries. JAMA 59:2015-2019. 1912. 

7)     Willius, F.A. and Keyes, T.E.: Cardiac Classics. The C.V. Mosby Company, St. Louis, USA . 1941.

8)     Hamman, L: The symptoms of coronary occlusion, Bull Johns Hopkins Hosp, 38:273,1926.

9)     Bruno Kisch - Strophanthin, Clinical and experimental experiences of the past 25 years, Brooklin Medical Press, New York City, N. Y., 1944.

10)   Ernst Edens - Die Strophanthin behandlung der Angina Pectoris, Munchener Medizinischen Wochenschrift, 81;1424, 1934.

11)   F. Anschutz und Y. Toker - Intersuchusen über die Wirksamkeit de Strophanthin_Behandlung beim Herzinfarkt mit der alternierenden Methode, Jg. 14, Heft 32; 7 August 1959.

12)   Dr. Peter Schmidsberger, Skandal Herzinfarkt, Die Hintergründe einer Epidemie und der Strophanthin-Streit, Verlag R.S.Schulz, 1975, book, at  http://www.melhorn.de/Strophskandal/SkandalHerzinfarkt.pdf   http://www.strophantus.de/mediapool/59/596780/data/SkandalHerzinfarkt.pdf  

13)   So Bekämpft ein Brasilianer den Herzinfarkt by Dr. Peter Schmidsberger. Bunte Magazine, Offenburg - Germany, 10/04/1980 at http://www.infarctcombat.org/Bunte/photo.html   

14)   Broder Clausen - Chronish Krank? Nein Danke! Erscheinungstermin, März 1997.

15)   Berthold Kern, Die orally strophanthin –behandlung, Ferdinand Enke Verlag - Stuttgart, 1951 at http://www.strophantus.de/mediapool/59/596780/data/Strophantin-Datei.pdf

16)   Berthold Kern, Der Myokard-Infarkt. Haug-Verlag, Heidelberg 1970 at http://www.strophantus.de/mediapool/59/596780/data/Myokard-Infarkt.pdf  

17)   G-strophanthin -A New Approach for Heart Disease at http://www.wrf.org/alternative-therapies/g-strophantinheart-disease.php

18)   Strophanthin history at http://www.cornavita.de/history/ 

19)   Rolf-Jürgen Petry - Strophanthin: der mögliche Sieg über den Herzinfarkt, Verlag Florilegium, 2003. Book. Summary in English with references at http://ouabain.twoday.net

20)   Berthold Kern, Herzinfarkt : 'Der Strophanthin ( = Ouabain ) – Report’ at http://www.strophanthin.de/   

21)   Eine dokumentation ambulanz-kardiologischer therapie ergebnisse nach anwendung oralen gstrophanthin, Herbert Pharma GmbH, Wiesbaden, 1984.

22)   Thomas Cowan on Cause and Prevention of Heart Attacks. Recorded at Freedom Law School's 2009 Health & Freedom Conference at https://www.youtube.com/watch?v=cgPW1tfg4JI  

23)   Memorial to Dr Quintiliano H. de Mesquita at www.infarctcombat.org/qhm/homepage.html 

24)   Quintiliano H. de Mesquita. Book Myogenic Theory of Myocardial Infarction, 1979. Summary in English at www.infarctcombat.org/LivroTM/parte8.htm  

25)   Quintiliano H. de Mesquita and Claudio A. S. Baptista. Why Myogenic Theory not Thrombogenic Theory. Arq Bras Cardiol, V. 62 (4), - Official Journal of the Brazilian Cardiology Society- Translated to English at http://www.infarctcombat.org/MTxTT-ABC.pdf  1994.

26)   Quintiliano H. de Mesquita et al. Effects of the Cardiotonic + Coronary Dilator in the Infarcting Clinical Picture. Article written in 1993, up-dated in 1998., Translated and published by ICP in 2013 at http://www.infarctcombat.org/ICP-CE.pdf

27)   Quintiliano H. de Mesquita et al. Effects of the Cardiotonic + Coronary Dilator in Unstable Angina. Article  written in 1993, up-dated in 1999. Translated and published by ICP in 2013 at http://www.infarctcombat.org/UA-CE.pdf

28)   Carlos Monteiro, “Stress as Cause of Heart Attacks - The Myogenic Theory”. Published at the Journal Wise Traditions in Food, Farming, and the Healing Arts, Fall 2014. Reproduced by Positive Health Online, Edition 222 - May 2015 at http://www.westonaprice.org/modern-diseases/cardiovascular-disease/stress-as-cause-of-heart-attacks / 

29)   “Stress: The Major Risk Factor for Heart Attack”. ICP, November 2014 http://www.infarctcombat.org/media/112014.pdf

30)    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

31)    Calderón-Montaño J, Burgos-Morón E, Lopez-Lazaro M. The Cardiac Glycosides Digitoxin, Digoxin and Ouabain Induce a Potent Inhibition of Glycolysis in Lung Cancer Cells. WebmedCentral CANCER 2013;4(7):WMC004323 at https://www.webmedcentral.com/wmcpdf/Article_WMC004323.pdf

32)   “Ernst Edens Traditionspreis” http://www.infarctcombat.org/Traditionpreis/photo.html

33)   Mesquita, QHde, Baptista CAS. Cardiotonic: Insuperable in preservation of myocardial stability, as preventive of acute coronary syndromes and responsible for a prolonged survival. Casuistry of 28 years Ars Cvrandi  2002 (1972-2000), May 35:3. Translated to English at www.infarctcombat.org/28years/digitalis.html   

34)   Quintiliano H. de Mesquita, et al. Effects of the Cardiotonic + Coronary Dilator in Chronic Stable CoronaryMyocardial Disease, with and without Prior Myocardial Infarction, in the Long Run. Ars Cvrandi, V. 35 - N 7 -

September 2002.English translation by ICP in 2013 at http://www.infarctcombat.org/CMD-CE.pdf

35)   Digoxin and increased mortality among  patients recovering from acute myocardial infarction: importance of digoxin dose, Cardiovasc Drugs Ther, 1995 Oct;9(5):723

36)   Quintiliano H. de Mesquita (1918-2000 “In Memoriam". Arquivos Brasileiros de Cardiologia vol. 76, nº 1 page 98,  Janeiro 2001 at http://www.scielo.br/pdf/abc/v76n1/3875.pdf  

37)   ANVISA: Esclarecimentos sobre a redução na oferta de Digoxina, 25 de junho de 2015 at http://goo.gl/cbXvVz  

38)   Mate Vamos, Julia W. Erath, Stefan H. Hohnloser. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. European Heart Journal

http://eurheartj.oxfordjournals.org/content/early/2015/04/30/eurheartj.ehv143  

39)   The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure, N Engl J Med 1997; 336:525533  at http://www.nejm.org/doi/full/10.1056/NEJM199702203360801  

40)   Dysfunction of the autonomic nervous system in atrial fibrillation, J Thorac Dis. 2015 Feb; 7(2): 193–198 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321068/   

41)   Melissa Walton-Shirley. The demonization of digitalis: plain stupid. Medscape May 19, 2015. http://www.medscape.com/viewarticle/844808 

42)   Arthur Dodek, Digitalis use in acute myocardial infarction: Current concepts. Can Med Assoc J. 1974 Sep 21;111(6):561, 563-4 at

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1947807/pdf/canmedaj01590-0061.pdf  

43)   Chapter ‘Cardiotonic in Acute Myocardial Infarction and Chronic Coronaropathy’ published in Dr. Mesquita’s book “Myogenic Theory of Myocardial Infarction”, 1979* - English Translation at http://www.infarctcombat.org/LivroTM/parte2-englishtranslation.htm