Effect of Synthetic Peptide LKEKK in Experimental Myocardial Infarction

Objective: The aim of this study was to study the effect of the LKEKK peptide on the rat myocardium in normal conditions and after experimental myocardial infarction (EMI). Methods: EMI was modeled in rats by ligating the anterior descending branch of the left coronary artery. Under ether anesthesia, the animal's skin and subcutaneous fat were incised, and the pectoral and intercostal muscles were separated along their fiber course. After opening the chest, the heart was removed through the surgical wound, and the left coronary artery was sutured and ligated. The onset of myocardial ischemia was monitored electrocardiographically. Results and Discussion: It was found that [3H]LKEKK binds with high affinity and specificity to the membranes of the rat myocardium before EMI (Ki = 1.9 nM). One hour after the operation, a sharp decrease in binding affinity was observed (Kd = 13.4 nM), after 24 h it increased significantly (Kd = 3.5 nM), and after 72 h it was almost completely restored (Kd = 2.1 nM). It was established that therapy of EMI with Riboxin (orally at a dose of 10 mg/kg once a day for 7 days after infarction) together with the peptide LKEKK (intranasally at a dose of 500 µg/rat according to the same scheme) has a pronounced anti-ischemic effect: improves coronary blood flow in the post-infarction period; increases myocardial contractility in the post-infarction period, promotes normalization of atrioventricular conduction disorders of the myocardium. A reliable decrease in the intensity of myocardial cytolysis and lipid peroxidation is also noted. All of the listed effects were more pronounced than in the case of Riboxin therapy without the peptide. Conclusions: The study demonstrates that the peptide can be used in complex therapy of ischemic heart disease and myocardial infarction.