Ischemic-induced alterations in cardiac sensitivity to digitalis

Area of Science:

• Cardiology
• Pharmacology
• Cellular Physiology

Background:

• Myocardial ischemia can alter cardiac cell function.
• Digitalis glycosides are crucial in treating heart failure but have a narrow therapeutic index.
• Understanding digitalis sensitivity post-ischemia is vital for patient safety.

Purpose of the Study:

• To investigate the effect of temporary myocardial ischemia on digitalis arrhythmogenic dose.
• To explore the role of the sodium pump (Na+,K+-ATPase) in altered digitalis sensitivity.

Main Methods:

• Inducing coronary artery occlusion and reperfusion in canine models.
• Administering acetylstrophanthidin intravenously and intracoronary.
• Measuring sodium pump activity using 86Rb uptake in ventricular slices.

Main Results:

• Ischemia and reperfusion significantly decreased the dose of digitalis required to induce ventricular arrhythmias.
• Sodium pump activity was significantly higher in ischemic compared to non-ischemic myocardial regions.
• The sensitivity of the sodium pump to ouabain inhibition increased in ischemic tissue.

Conclusions:

• Temporary myocardial ischemia increases myocardial sensitivity to the toxic effects of digitalis.
• This increased sensitivity appears related to enhanced Na+,K+-ATPase sensitivity to digitalis inhibition.
• Findings suggest a need for careful digitalis dosing in patients with ischemic heart disease.