Article originally published in the Heartnews Section of Infarct
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Endogenous Cardiotonic Hormones: A New Argument for the Myogenic Theory of Myocardial Infarction
The first to postulate the existence of an endogenous digitalis in mammals was Ringer in 1885.
Alberto Szent-Györgyi advocated a similar idea in 1953 (1).
Cardiotonic steroids of the cardenolide (digoxin and ouabain) and bufadienolide (Proscilaridine-A
and Marinobufagenin) types have been isolated from human tissues and body fluids (2, 3, 4, 5).
Elevated concentrations of endogenous ouabain have been found under different conditions like sodium
imbalance, chronic renal failure and congestive heart failure. Taking in view the significant
relations of plasma ouabain concentration with cardiac index and mean arterial pressure it was
assumed that endogenous ouabain may be an important homeostatic factor in humans (6, 7, 8).
The endogenous ouabain changes rapidly in human and dogs upon physical exercise and is in control of
epinephrine and angiotensin II. Hence, the steroid acts as a rapidly acting hormone (9).
A clinical study published in 2003 attempted to determine the incidence of critically ill patients
displaying endogenous digitalis-like immunoreactive substances (DLIS) and to examine the
relationship of these hormones to routine laboratory variables, the underlying disease, myocardial
function, hemodynamic status, severity of illness, systematic inflammation, and mortality rate. The
blood of 401 pacients, not treated with cardiac glycosides, were analysed for DLIS (digitoxin and
digoxin) and endogenous ouabain. It was concluded that different types of endogenous glycosides
including endogenous ouabain are elevated in a significant proportion of critically ill patients.
The occurrence of these susbstances is associated with increased morbidity and hospital mortality
rates, possible due to systemic inflammatory processes. The study also found that DLIS but not
endogenous ouabain concentrations are related to left ventricular function (10).
A study published in 1991 demonstrated there was a 2.5 fold increase in plasma digoxin-like
immunoreactivity in patients with myocardial infarction as compared with five healthy controls and
nine patients with unstable angina (11).
In a study published in 1992, it was examined endogenous digitalis-like factor concentrations in the
serum and urine in 65 patients with acute myocardial infarction. Radioimmunoassay was used for the
examination and patients’ data were analyzed in relation
The concentrations of digitalis-like factor found in the serum of men and women with acute
myocardial infarction were much higher compared with values of healthy men and women. According the
authors these findings are in agreement with data published by others and suggest a role of digitalis-
like factor in the pathogenesis of myocardial infarction (12,13).
A study published in 1994 showed an increase of plasma EDLF (concentration of endogenous digoxin-
like factor) during the 1st day after acute myocardial infarction, and that higher plasma EDLF may
be associated with the development of ventricular arrhythmias (14).
A study published in 1990 measured the ability of plasma to inhibit a human renal NA (+) - K +
ATPase before and immediately after percutaneous transluminal coronary angioplasty (PTCA) in 6
patients suffering angina pectoris and severe coronary stenosis. Related to the increase of
concentration of the digitalis-like factor in plasma the authors placed the hypothesis that the
reduction in cardiac output during PTCA by raising cardiac pressures may stimulate the production of
a factor of compensatory inotropic significance (15).
In a study from 1988 the perioperative digoxin concentrations were measured in 20 unselected adult
patients undergoing coronary surgery. None of the patients were receiving treatment with digoxin. A
digoxin-like immunoreactive substance was found in 16 patients postoperatively (16).
A study published in 1998 have described the purification of the marinofufagenin bufadienolide from
the urine of patients with myocardial infarction and with increased concentration in the blood
plasma. The authors placed that these data suggest a role for this substance in the pathogenesis of
myocardial ischemia (5).
Another study published in 2002 measured the plasma levels of marinobufagenin in 23 consecutive
hypertensive male patients with CHF (congestive heart failure) showing progressive increases in a
graded manner with the severity of CHF (17) .
We also have the cardiotonic apelin, a peptide endogenous hormone discovered in 1998, found in high
concentration in the cardiac tissue
(18).
Study published in 2002 show that apelin is one of the most potent endogenous positive inotropic
substances yet identified and that it regulates cardiac contractility (19)
A study published in 2003 reported for the first time circulating human apelin levels and
demonstrating increases in the plasma level of apelin in patients with left ventricular dysfunction
with it emerging as an important novel mediator of cardiovascular control (20).
Another recent study show that apelin levels were increased in
19.7-fold in chronic heart failure due to coronary heart disease and
20.3-fold due to idiopathic dilated cardiomyopathy, whereas atrial apelin levels were unchange. The
authors of the study tell their results suggest that apelin and APJ receptor may contribute to
the pathophysiology of human congestive heart failure (21).
The studies about endogenous cardiotonic hormones are just starting. However, it is possible to
predict, with a high degree of certainty, the studies will confirm the exogenous cardiotonics as
anti-infarction drugs, complementing, opportunatelly, an eventual and insufficient production of
the endogenous cardiotonic hormones by the human body, in order to support the cardiac metabolism
and protect the heart from the infarction as defended by the Myogenic Theory of Myocardial
Infarction (23).
"Cardiotonic drugs represent to heart disease the same as insulin for diabetes.. "
Bibliography
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43. The Myogenic Theory of Myocardial Infarction at infarctcombat.orgMyogenicTheory.htmlOpen ↗