Cardioprotective Effects of Metalloproteinase Inhibitor 1-({4-[(4-Chlorobenzoyl)amino]phenyl}sulfonyl-L-Proline in Modeled Acute Myocardial Infarction.

Cardioprotective effect of 1-({4 [(4 chlorobenzoyl)amino]phenyl}sulfonyl-L-proline (compound AL-828) was studied in rats with modeled acute myocardial infarction. The test compound was administered intragastrically in a dose of 30 mg/kg/day for 3 days prior to infarction modeling. Metalloproteinase inhibitor antibiotic doxycycline served as the reference drug and was administered in a dose of 40 mg/kg/day by the same schedule. It was shown that AL-828 similar to doxycycline significantly reduced the intensity of myocardial remodeling and maintained the inotropic function of the myocardium in the acute phase of myocardial infarction. By the 20th minute of ischemia, the end-systolic dimension of the left ventricle in control animals increased from 1.98±0.12 to 3.84±0.16 mm, while in animals treated with AL-828, this increase was significantly (p=0.007) less pronounced (from 1.84±0.07 and 2.87±0.21 mm, respectively). The ejection fraction characterizing the inotropic status of the left ventricle in animals treated with AL-828 was significantly higher (p=0.02). By its cardioprotective activity, AL-828 was not inferior to the reference drug doxycycline. It can be assumed that the cardioprotective activity of compound AL-828 is related to suppression of MMP-9 expression and/or inhibition of its activity as was previously demonstrated by us.