Abstract

COVID-19 is a disease characterized by damage to the lower respiratory tract, development of the acute respiratory distress syndrome, in severe cases — multiple organ failure, including acute heart failure and cardiomyopathy. This study aimed to evaluate the effectiveness of the developed COVID-19 pathogenetic therapy and complications prevention agents using the ex vivo isolated lung and heart models. Isolated organs of white rats were used for the research; the dynamics of functional indicators were analyzed. An amino acid-peptide complex (APC) from a thermally treated milk protein hydrolyzate was used as the experimental COVID-19 pathogenetic therapy and complications prevention agent. Introduction of the APC to the isolated cardiopulmonary complex perfusate slowed down development of pulmonary edema in the experimental group; the organ's weight was 1.5 times less than in the control group (p = 0.0158). We have also registered an airway resistance downtrend. APC supported contractile activity of the isolated myocardium suffering ischemia-reperfusion: the growth of the left ventricular end diastolic pressure was 34% smaller than that registered in the control group (p < 0.05). The APC's cardioprotective effect relies on the endothelium-dependent mechanisms. The ex vivo method is highly informative. It allows assessing reactivity of the isolated organs exposed to biologically active substances and determining the possibilities of compensating for functional changes.

Highlights

  • COVID-19 is a disease characterized by damage to the lower respiratory tract, development of the acute respiratory distress syndrome, in severe cases — multiple organ failure, including acute heart failure and cardiomyopathy

  • We identified that the resistance of airways of the isolated lungs tends to decrease when the perfusate is supplemented with acid-peptide complex (APC) components, which may indicate that pulmonary edema is less severe in the experimental group (Fig. 5)

  • The heart model isolated in the Langendorff system allowed establishing that the active components of the APC at the concentration of 1 × 10–6 M, which corresponds to the 50 mg/kg dose when administered intragastrically, do not significantly affect functional parameters of an intact rat heart but promote an end-diastolic pressure drop (p < 0.05) under ischemia-reperfusion (Fig. 6) and support the rate at which the myocardium contracts and relaxes during the cardiac cycle (Table 2)

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Summary

Introduction

COVID-19 is a disease characterized by damage to the lower respiratory tract, development of the acute respiratory distress syndrome, in severe cases — multiple organ failure, including acute heart failure and cardiomyopathy. This study aimed to evaluate the effectiveness of the developed COVID-19 pathogenetic therapy and complications prevention agents using the ex vivo isolated lung and heart models. Introduction of the APC to the isolated cardiopulmonary complex perfusate slowed down development of pulmonary edema in the experimental group; the organ's weight was 1.5 times less than in the control group (p = 0.0158). The ex vivo method is highly informative It allows assessing reactivity of the isolated organs exposed to biologically active substances and determining the possibilities of compensating for functional changes. Целью работы было оценить эффективность разрабатываемых средств патогенетической терапии и профилактики осложнений COVID-19 с использованием моделей изолированных легких и сердца ex vivo. С. Лаптев — экспериментальная часть, сбор информации, обработка данных; С. Г. Петунов — обработка и интерпретация данных, общее руководство; О.

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