Direct chronotropic and inotropic effects of mildronate using cross-circulated dog atrial and ventricular preparations.

The cardiac effects of mildronate were studied in isolated and blood-perfused atrial and ventricular preparations from mongrel dogs. Mildronate (10(-9)-10(-6) mol) did not induce any chronotropic or inotropic responses in spontaneously beating isolated right atria at 37 degrees C. However, it produced negative chronotropic and inotropic effects at large doses (10(-5)-10(-4) mol). Mildronate-induced responses were not significantly inhibited by treatment with atropine, suggesting that they do not involve muscarinic mechanisms. Mildronate produced only a slight negative inotropic effect in electrically paced, isolated left ventricular preparations at extremely large doses. Intravenous injections of 10(-4) mol/kg mildronate to the support (donor) dog induced a slight, non-significant, depressor effect, and did not significantly influence either atrial pacemaker activity or atrial developed tension. From these results, it is concluded that a therapeutic dose of mildronate has no direct influence on SA nodal pacemaker activity and atrial contractility, but that it has a slight cardiac depressant property at large doses.