Myocardial infarct size-limiting and anti-arrhythmic effects of mildronate orotate in the rat heart.
OBJECTIVE
Mildronate and orotic acid act as modulators of energy metabolism and are considered as cardioprotective agents. This study was performed to compare the cardioprotective effects of mildronate, orotic acid and mildronate orotate.


METHODS
Male Wistar rats received mildronate, orotic acid or mildronate orotate for 14 days. The isolated rat heart infarction and isoproterenol-induced ischemia models were used to test the cardioprotective effects of compounds studied. Experimental arrhythmias were induced by the ligation of the left anterior descending coronary artery for 10 min with subsequent reperfusion or by administration of calcium chloride or aconitine at arrhythmogenic doses.


RESULTS
The data obtained showed a statistically significant decrease of necrotic area in 25% of infarcted rat hearts after 14 days of treatment with mildronate and orotic acid, whereas mildronate orotate decreased the infarct size by 50%. Moreover, we found that the administration of mildronate and its orotate salt decreased the duration and incidence of arrhythmias in experimental arrhythmia models.


CONCLUSIONS
The study provides experimental evidence that the combination of orotic acid and mildronate possesses additive pharmacological effects and that mildronate orotate might be considered as a powerful therapeutic agent facilitating recovery from ischemia-reperfusion injury.
Vilskersts
Reinis
R
Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga, LV1006, Latvia.
Liepinsh
Edgars
E
Kuka
Janis
J
Cirule
Helena
H
Veveris
Maris
M
Kalvinsh
Ivars
I
Dambrova
Maija
M
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008297:Male; D008763:Methylhydrazines / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009336:Necrosis / Q000188:drug therapy; D009963:Orotic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy
D002316:Cardiotonic Agents; D008763:Methylhydrazines; D009963:Orotic Acid; C050147:3-(2,2,2-trimethylhydrazine)propionate