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Does Digoxin know, which ventricle it is supposed to act in patients with cor- pulmonale ?

Posted Jun 06 2010 10:43am

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)

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