Digoxin is a wonder cardiology drug used for more than a century.We know the pioneering efforts of William withering in detecting the potential of the unknown herb Foxglove.
Mechanism of action
The beneficial effects of Digoxin is attributable to
- Positive inotropic action
- Vagal action
Digoxin blocks the sodium potassium ATPase in the myocyte cell membrane .
This cause accumulation of NA + ions within the cells. The excess Na , then facilitates the Na -Ca exchange port .
This pumps in more calcium into the myocyte.
Increased calcium means more forceful contraction and that is positive inotropism* .
* This is a highly simplified version of Digoxin’s action . It should be remembered simple availability of excess calcium can not guarantee contractility, as it requires adequate number of receptors.
Digoxin is used in which type of cardiac failure ?
Digoxin is used for both for LV and biventricular failure .
Digoxins is still often in isolated RV failure of any cause (Cor pumonale, PPH, Eisenmenger etc)
Digoxin and RV dysfunction
Digoxin has a tendency to hit the atrial muscles at random causing multiple short circuiting (Micro reentry ) forming a perfect nidus for complex atrial arrhythmias including MAT .The coexisting hypoxia (which is all the more common here ) aggravates the problem .
Inotropism of RV : Does it really exist ?
It is often quoted , RV is a passive pump. It does not mean inotrpism is an exclusive property of LV.
RV has to generate about 30mmhg to pump the blood into the lungs.
In cor-pulmonale the RV works against an afterload of around 50-70 mmhg , making RV inotropism much more important concept.
Rate control in atrial fibrillation Digoxin lowers the heart rate by vago mimetic action , primarily in AV node and to a certain extent in SA node .Ventricular rate reduction is the prime requirement in the management atrial fibrillation and this property is still the crowing glory of Digoxin.
Though beta blockers and verapamil can be used as rate controlling agent , lack of negative inotropism makes digoxin prevail over , especially in severely dysfunctional ventricle .
But , one disadvantage of Digoxin is , since it requires a vagal traffic to mediate it ‘ s rate controlling effect , it is less effective , when there is high sympathetic activity as during exercise.
What is the action of digoxin on interventricular septal contraction ?
Digoxin , simply does not know where it acts when administered in cor pulmonale ! We believe in cor-pulmonale the maximum action would be the area of maximum dysfunction .This is purely an assumption. In cor -pulmonale septum shifts it’s loyalty from LV to RV as the later is the distressed chamber.So , logic would be there is a theoretical compromise of LV function in patients with cor -pulmonale. These factors make the inter ventricular interaction and dependence a complex one.
Some believe the improvement of sub clinical LV dysfunction in cor pulmonale may be more important factor in giving relief to the patient’s symptom.
What are the other RV inotropes ?
Doubtamine has some RV inotropy .This again may be due to a spill over effect from LV rather than a primary RV inotropism .
As such , there is no great breakthrough in creating a powerful isolated RV isolated RV inotropic dug.
Probably the best way to give relief to RV is to reduce the pulmonary artery pressure as invariably sever PAH is the predominate accompaniment
(Nitric oxide , Epo prostenol etc)
Final message
- Digoxin , indeed has some useful role in cor- pulmonale .
- But ,the benefits are more pronounced in late stages of RV failure.
- Since the dose required to get an optimal RV inotropy is high the safety margin is reduced.
- Since there is a propensity for complex atrial arrhythmias , it has to be used very cautiously in management of atrial fibrillation due to cor pulmonale .(Than in other forms of AF)
Dr.S.Venkatesan MD 