Using experimental ex vivo models to develop COVID-19 pathogenetic therapy and complications prevention agents

Laptev DS, Petunov SG, Nechaykina OV, Bobkov DV, Radilov AS
About authors

Research Institute of Hygiene, Occupational Pathology and Human Ecology Leningrad Region, Russia

Correspondence should be addressed: Denis S. Laptev
st. Kapitolovo, gor. pos. Kuzmolovsky, 93, Vsevolozhsky rajon, 188663; ur.liam@nedpal

About paper

Author contribution: Laptev DS — experimental part, information collection, data processing; Petunov SG — data processing and interpretation, general guidance; Nechaykina OV — experimental part, information collection; Bobkov DV — data processing; Radilov AS — data processing and interpretation.

Compliance with ethical standards: all work with animals was carried out in conformity to the provisions of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes.

Received: 2020-09-15 Accepted: 2020-12-25 Published online: 2020-12-12

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.

Keywords: ischemia, COVID-19, isolated heart, isolated lung, pulmonary edema