Influence of the Immobilized Subtilisins on the Coronary Blood Flow in Experiment

In Russia, the drug Trombovazim, which has a direct thrombolytic effect, is registered and used in clinical practice. Indications for use in cardiology are acute myocardial infarction with ST elevation, in phlebology - chronic venous diseases. The active substance of the drug Trombovazim is immobilized subtilisin. Subtilisin is a proteolytic enzyme with a direct fibrinolytic effect. To reduce the allergenic properties and increase the enteric bioavailability of subtilisin, electron-beam immobilization of the enzyme is carried out on a polyethylene glycol polymer carrier. In the instruction for medical use of the drug, there is no indication of its effect on coronary blood flow. Because the drug is positioned for the treatment of cardiovascular diseases, we found it would be interesting and important to evaluate the effect of immobilized subtilisin on coronary circulation in experiments on the isolated laboratory rat heart using the Langendorff method. The choice of this experimental model is due to the possibility of a direct assessment of the vasomotor action of immobilized subtilisin in the absence of humoral and nervous regulation of the coronary circulation in isolated heart. There are practically no data in the literature about the subtilisin's influence on the coronary blood flow. These experimental studies present data about the effect of immobilized subtilisins on coronary blood flow at the various concentrations. At doses of 170 IU/L and 340 IU/L we noticed an increase in coronary flow and, accordingly, the vasodilating effect of immobilized subtilisins. We have observed the phenomenon of vasomotor activity of ImSubt in relation to the coronary vessels. In the next experiments we will try to find the specific receptors for immobilized subtilisins in the coronary vessels.