Inotropic and chronotropic effects of vasodilators

Area of Science:

• Cardiovascular Pharmacology
• Cardiac Electrophysiology

Background:

• Vasodilators are increasingly used for heart failure and myocardial ischemia.
• Direct effects of vasodilators on cardiac muscle require further characterization.

Purpose of the Study:

• To delineate the direct chronotropic and inotropic effects of various vasodilators on mammalian myocardium.
• To differentiate the myocardial actions of calcium antagonists from classical vasodilators.

Main Methods:

• Isolated guinea-pig atria (n=163) were used to assess chronotropic and inotropic effects.
• Spontaneous frequency and isometric force development measured as indexes of chronotropy and inotropy.
• Concentration-dependent effects of various vasodilators evaluated up to 10(-5) M.

Main Results:

• Potency series for negative chronotropy: diltiazem > D600 > verapamil > lidoflazine > bepridil > prenylamine > perhexiline > nifedipine.
• Potency series for negative inotropy: nifedipine > D600 > verapamil > bepridil > lidoflazine > prenylamine > perhexiline > diltiazem.
• Nifedipine demonstrated "inoselective" and diltiazem "chrono-selective" depression; other vasodilators showed negligible direct myocardial effects.

Conclusions:

• Calcium antagonists possess significant direct myocardial effects, distinguishing them from classical vasodilators.
• Nifedipine and diltiazem exhibit differential selectivity for inotropic versus chronotropic effects.
• This study supports classifying calcium antagonists as a distinct category of cardiovascular agents.