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

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The cardiac effects of mildronate were studied in isolated and blood-perfused atrial and ventricular preparations from mongrel dogs. Mildronate (10-9-10-6mol) did not induce any chronotropic or inotropic responses in spontaneously beating isolated right atria at 37°C. However, it produced negative chronotropic and inotropic effects at large doses (10-5-10-4mol). 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 10-4mol/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.