Mildronate, a novel fatty acid oxidation inhibitor and antianginal agent, reduces myocardial infarct size without affecting hemodynamics.
Mildronate is a fatty acid oxidation inhibitor approved as an antianginal drug in parts of Europe. We carried out the first study to determine whether a 10-day course of mildronate could reduce myocardial infarct size (IS) during acute myocardial ischemia. Sprague Dawley rats received 200 mg/kg/d of mildronate (treated group, n = 16) or sterile water (control group, n = 14) subcutaneously for 10 days before ischemia-reperfusion. Rats were then subjected to 45 minutes of left coronary artery occlusion and 2 hours of reperfusion. The 2 groups had identical areas at risk: treated 38 +/- 3%; controls 38 +/- 2%. The amount of necrosis was smaller in the mildronate group at 16 +/- 2% of the left ventricle versus controls, 22 +/- 2% (P = 0.05); and for any amount of risk >25%, necrosis was smaller in the treated group (P = 0.0035). Myocardial IS (% of risk zone) was 43+/-3% in the mildronate-treated rats, and 57+/-4% in controls (P = 0.004). During occlusion, there were no differences between the 2 groups in heart rate (216 +/- 12 bpm, mildronate and 210 +/- 9 bpm, control), in mean arterial pressure (60 +/- 2 mm Hg, mildronate and 64 +/- 3 mm Hg, control) or in the frequency of arrhythmias. Our study for the first time demonstrated that a 10-day treatment with mildronate reduced myocardial IS in an experimental model of acute myocardial ischemia, without any effect on hemodynamics.
Sesti
Casilde
C
The Heart Institute, Good Samaritan Hospital, Keck School of Medicine, University of Southern California, Los Angeles, 90017, USA.
Simkhovich
Boris Z
BZ
Kalvinsh
Ivars
I
Kloner
Robert A
RA
D000787:Angina Pectoris / Q000188:drug therapy*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008763:Methylhydrazines / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D002317:Cardiovascular Agents; D005227:Fatty Acids; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate