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.
Chiba
S
S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Akahane
K
K
Furukawa
Y
Y
Karasawa
Y
Y
D000818:Animals; D016275:Atrial Function; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D003864:Depression, Chemical; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008763:Methylhydrazines / Q000008:administration & dosage / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion / Q000379:methods; D016276:Ventricular Function
D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate; D001285:Atropine; D002217:Carbachol