Digitalis has the unique characteristic of increasing contractility (positive inotropy) while decreasing heart rate (negative chronotropy). This pharmacological profile results from indirect as well as direct effects of digitalis glycosides on the heart. Digitalis is a fat-soluble steroid that crosses the blood-brain barrier and enhances vagal tone. The slowing and/or conversion of a patient with supraventricular arrhythmia (e.g., atrial fibrillation, supraventricular tachycardia) with digitalis results from enhancement of vagal tone. This increased vagal activity increases acetylcholine release, which in turn is coupled to the opening of a K+ channel. Opening of this K+
channel results in closing of the L-type sarcolemmal Ca++ channel. Ca++ channel inhibition slows the heart rate and/or converts the rhythm to a sinus mechanism.
Digitalis works directly on the heart through an action on the sodium-potassium (Na+-K+) ATPase. Since all living cells have a resting membrane potential, there is an electrochemical gradient across the cell membrane that is not at a steady state electrically. There is an imbalance in that all cells are intracellularly negative compared to the outside of the cell. The maintenance of this gradient requires metabolic energy to maintain this difference in ions. This electrochemical gradient is lost after death. The activity of the Na+-K+ ATPase results in serum sodium levels of roughly 140 to 145 mmol and serum potassium around 5 mmol. Inside cells the Na+ concentration is low and the K+ concentration is high. The reason for this difference between the intracellular and extracellular sodium and potassium is the action of the Na+-K+ ATPase enzyme. Digitalis binds to this enzyme and inhibits its activity. This results in an elevation in intracellular Na+ that leads to an increase in extrusion of Na+ through the Na+-Ca++ exchanger, which functions to maintain a relatively constant level of both Na+ and Ca++ in the cell. The Na+-Ca++ exchanger normally extrudes Ca++ in exchange for Na+. However, in the presence of increased intracellular Na+, it will extrude Na+ by exchanging it for extracellular Ca++. This reversal in the activity of the Na+-Ca++ exchanger results in an increase in intracellular ionized free Ca++ that enhances myocardial contractility.
The current hypothesis regarding the cellular basis for the positive inotropic effect of digitalis helps to explain some of the wide individual variability in the dosage required to develop digitalis toxicity. Differences in pH, ischemia, Na+, K+ , and Ca++ can each alter the likelihood of developing toxicity within the same patient and between individuals.
Was this article helpful?
This guide will help millions of people understand this condition so that they can take control of their lives and make informed decisions. The ebook covers information on a vast number of different types of neuropathy. In addition, it will be a useful resource for their families, caregivers, and health care providers.