Experimental study of the immobilized subtilisins’ effect on the performance of an isolated rat heart

I n t r o d u c t i o n .  Currently, a new pharmacological technology of thrombolytic therapy using immobilized subtilisins (ISs) has been introduced into clinical practice. Experimental and clinical studies have shown the high efficacy and safety of the treatment of thrombotic diseases using the drug Thrombovasim®, created on the basis of ISs. Although this drug has been widely studied as a thrombolytic, its pluripotent pharmacological properties have not been studied in detail.

A i m .  To study the performance of an isolated rat heart under the coronary perfusion with ISs.

M a t e r i a l s   a n d   m e t h o d s .   The Langendorff’s perfused heart model was used in the study. The experiment included 50 Wistar rats. Animals were divided into 5 groups (10 animals each): group 1 – control (hearts perfused with Krebs-Henseleit solution) and 4 experimental groups – hearts perfused with ISs at 4 concentrations of 170, 340, 510 and 1020 IU/l respectively. The performance indicator of an isolated heart was assessed, reflecting the actual work of the heart muscle and expressed as the product of the heart rate and the strength of its contractions in the form of the pressure developed by the left ventricle.

R e s u l t s .  No negative ISs effect on the performance of the isolated rat heart was found. A tendency to increase the performance in the first 5 minutes of using ISs was revealed. The achievement of the maximum and the duration of this effect depend on the ISs contents in perfusate. At a concentration of 170 IU/l, an obvious increase in the effect is found from the 10th minute, at higher concentrations – from the 5th minute. The duration of the increasing performance effect when using doses of 170–510 IU/l is maintained up to the 20th minute, when using ISs at a dose of 1020 IU/l – up to the 30th minute. The return of the performance indicators to the baseline values is observed at the 30th minute, at a dose of 340 IU/l – at the 40th minute. When perfused with a solution of ISs at concentrations of 510 and 1020 IU/l, by the 40th minute, the effect of increasing performance weakens, but the parameters still remain at higher levels as compaired to those at baseline.

C o n c l u s i o n .  The experimental data obtained show that ISs increase the performance of the heart. This circumstance will allow expanding the use of the drug Thrombovasim® in a catastrophe of the coronary circulation.

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