A 54-year-old man with nonischemic cardiomyopathy comes to the office for a follow-up visit. He has been hospitalized frequently for acute decompensated heart failure, and currently has dyspnea on mild exertion. The patient also has a history of hypertension and takes multiple medications. Blood pressure is 116/70 mm Hg, and pulse is 72/min and regular. Physical examination shows elevated jugular venous pressure, bibasilar lung crackles, and lower extremity edema. Serum creatinine is 1.0 mg/dL and serum potassium is 4.2 mEq/L. Three weeks after starting digoxin therapy, the patient reports symptomatic improvement. Which of the following is the initial cellular event triggering this response to the new medication?

Question

A 54-year-old man with nonischemic cardiomyopathy comes to the office for a follow-up visit.  He has been hospitalized frequently for acute decompensated heart failure, and currently has dyspnea on mild exertion.  The patient also has a history of hypertension and takes multiple medications.  Blood pressure is 116/70 mm Hg, and pulse is 72/min and regular.  Physical examination shows elevated jugular venous pressure, bibasilar lung crackles, and lower extremity edema.  Serum creatinine is 1.0 mg/dL and serum potassium is 4.2 mEq/L.  Three weeks after starting digoxin therapy, the patient reports symptomatic improvement.  Which of the following is the initial cellular event triggering this response to the new medication?

Quizplus · Accepted Answer

11ec160b_3b85_d304_9249_3705f3db285a_MD0001_00 Digoxin is a positive inotropic agent that provides symptomatic relief in patients with acute decompensated heart failure due to left ventricular systolic dysfunction. It also increases parasympathetic tone and slows conduction through the atrioventricular node, which can help improve cardiac function in patients with a rapid ventricular rate. Digoxin directly inhibits the Na-K-ATPase pump in myocardial cells, leading to decreased sodium efflux and an increase in intracellular sodium levels. The decreased transmembrane sodium gradient reduces the forward activity of the sodium-calcium exchanger, leading to a secondary decrease in calcium efflux from the cells. Increased intracellular calcium concentration stimulates the binding of calcium to troponin C and subsequent actin-myosin cross-bridge formation, resulting in improved myocyte contractility and left ventricular systolic function. (Choice B) The increase in intracellular sodium caused by digoxin reduces the forward activity of the sodium-calcium exchanger, resulting in increased intracellular calcium concentration. However, the calcium increase is a secondary effect of digoxin that occurs after the increase in intracellular sodium. (Choice C) Cyclic AMP (cAMP), an important second messenger in excitation-contraction coupling, is formed from ATP by adenylyl cyclase. Adenylyl cyclase activity is stimulated by beta agonists and inhibited by acetylcholine. cAMP increases the conductance of the calcium channels in the sarcoplasmic reticulum. As a result, more calcium is available to bind to troponin C, strengthening the force of contraction. (Choice D) Inhibition of the Na-K-ATPase pump by digoxin leads to a decrease in potassium influx into myocardial cells. (Choice E) Digoxin does not cause increased troponin sensitivity to calcium; instead, it increases the amount of intracellular calcium available for troponin binding. Educational objective: Digoxin directly inhibits the Na-K-ATPase pump in myocardial cells, leading to a decrease in sodium efflux and an increase in intracellular sodium levels. This reduces the forward activity of the sodium-calcium exchanger, causing increased intracellular calcium concentration and improved myocyte contractility.

A 54-Year-Old Man with Nonischemic Cardiomyopathy Comes to the Office