Influence of Recombinant Interferon Alfa on Electric Activity and Isolated Heart Metabolism

It was studied an effect of recombinant interferon-α2b on the isolated mouse heart. Retrograde perfusion of the heart with Krebs-Henselite solution with dissolved interferon-α2b (2000 IU) caused a decrease in the voltage of the R wave at the time of perfusion and ischemia (but when reperfusion leads it to increase), an increase the duration of the R-R interval. At the same time, perfusion of the heart with a solution of interferon-α2b was accompanied by a decrease in the volume rate of the coronary flow. Passing of interferon-α2b through the heart leads to a decrease in myocardial glucose consumption against the background of deposition of extracellular Ca2+ and an increase in the yield of the enzyme AcAt, a decrease in creatinine excretion, which indicates inhibition of CPK activity. Since the overwhelming amount of CK is localized in the mitochondrial membranes, the results which were obtained indicate an inhibitory effect of interferon on the activity of transport processes of macroergic compounds in the myocardium. Materials and methods. Examinations were conducted on the hearts of non-linear laboratory mice (n=20) aged 3-4 months, with body weight 20-25 g. After conducting cervical dislocation isolated heart, which was placed in chilled (+40 C) solution of Krebs-Henseleit (pH 7,3-7,4) with heparin. Immediately cannulated of the aorta, and it was begun a retrograde perfusion of the coronary blood vessels under conditions of constant pressure, 102±2 mm Hg. article warm (+370С) perfusion with a solution of Krebs-Henseleit (composition of solution in mmol/l: NaCl – 118; KCl - 4.7; and MgSO4 - 1.2; KH2PO4 - 1.2; CaCl2 – 2.5); a glucose of 5.5; NaHCO3 – 25). The perfusion solution was continuously saturated with carbogen (95% O2 and 5% CO2). Electrical activity investigated heart in natural state and artificial stimulation was not conducted. Heart electrogram was registered during perfusion. Determination of the volume of velocity was performed of the coronary flow by measuring of the volume of flow from the coronary vessels of solution (ml/min). In the resulting perfusion, solution determined the content of calcium, creatinine, glucose, and aspartate aminotransferase (AST). The first (control) group consisted of samples isolated heart (n=10), through which passed a solution of Krebs-Henseleit. The second group included (n=10), through which passed a solution of Krebs-Henseleit which was dissolved lyophilized preparation of recombinant interferon-α2b at a concentration of 2000 IU/L. Ischemia-reperfusion of the isolated heart, which was immersed in capacity with perfusion solution, was modelled by a complete cessation of perfusion for 20 minutes. The duration of perfusion and reperfusion was 20 minutes. Results and discussion. A solution of interferon-α2b determines changes of electrogram of isolated hearts of mice, the decrease in voltage of R-wave at the time of the perfusion and ischemia (however, during reperfusion it causes increase), the increase in the duration of R-R interval in all cases. Changes in the indices of electrogram isolated heart under the influence of interferon--α2b are consistent with the decline in flow rate of the coronary flow, especially during reperfusion. Interferon-α2b causes metabolic changes in the isolated heart, which is manifested by reduced consumption of glucose on the background deposition of extracellular Ca2+ myocardium and increased release of the enzyme AST in the perfusion solution. However, passing through the heart of the solution of interferon caused decline of creatinine excretion from the myocardium, indicating the inhibition of the activity creatine kinase. Due to the fact that an overwhelming number of creatine kinase localized in the mitochondrial membranes, the obtained results indicate the inhibitory effect of IFN on the activity transport processes of macroergic compounds in the myocardium.