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
  1. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017; 39: 529–39. DOI: 10.1007/s00281-017-0629-x.
  2. Su S, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016; 24 (6): 490–502. DOI: 10.1016/j.tim.2016.03.003.
  3. Gu J, et al. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005; 202 (3): 415–24. DOI: 10.1084/jem.20050828.
  4. Nicholls JM, et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet. 2003; 361 (9371): 1773–8. DOI: 10.1016/ S0140-6736(03)13413-7.
  5. Akhmerov A, Marban E. COVID-19 and the Heart. Circ Res. 2020; 126 (10): 1443–55. DOI: 10.1161/circresaha.120.317055.
  6. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020; 5 (7): 811–8. DOI: 10.1001/jamacardio.2020.1017.
  7. Li J, Benashski SE, Venna VR, McCullough LD. Effects of metformin in experimental stroke. Stroke. 2010; 41: 2645–52.
  8. Fung G, Luo H, Qiu Y, Yang D, McManus B. Myocarditis. Circ Res. 2016; 118: 496–514. DOI: 10.1161/CIRCRESAHA.115.306573.
  9. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020; 5 (7): 802–10. DOI: 10.1001/jamacardio.2020.0950.
  10. Gundewar S, Calvert JW, Jha S, Toedt_Pingel I, Ji SY, Nunez D, et al. Activation of AMP activated protein kinase by metformin improves left ventricular function and survival in heart failure. Circ Res. 2009; 104: 403–11.
  11. Goransson O, McBride A, Hawley SA, Ross FA, Shpiro N, Foretz M, et al. Mechanism of action of A769662, a valuable tool for activation of AMP activated protein kinase. J Biol Chem. 2007; 282: 32549–60.
  12. Barnes K, Ingram JC, Porras OH, Barros LF, Hudson ER, Fryer LG, et al. Activation of GLUT1 by metabolic and osmotic stress: potential involve ment of AMP activated protein kinase (AMPK). J Cell Sci. 2002; 115: 2433–42.
  13. Procopio C, Andreozzi F, Laratta E, Cassese A, Beguinot F, Arturi F, et al. Leptin stimulated endothelial nitric oxide synthase via an adenosine 5' monophosphate activated protein kinase/Akt signaling pathway is attenuated by interaction with C reactive protein. Endocrinology. 2009; 150: 3584–93.
  14. Nelson K, Bobba C, Eren E, Spata T, Tadres M, Hayes DJr, et al. Method of isolated ex vivo lung perfusion in a rat model: lessons learned from developing a rat EVLP program. J Vis Exp. 2015; 25 (96): 52309. DOI: 10.3791/52309.
  15. Chianga C, Pai H, Liu S. Ventilator-induced lung injury (VILI) promotes ischemia/reperfusion lung injury (I/R) and NF-kB antibody attenuates both injuries. Resuscitation. 2008; 79: 147–154.
  16. Ishikita A, Matoba T, Ikeda G, Koga JI, Mao Y, Nakano K, et al. Nanoparticle-Mediated Delivery of Mitochondrial Division Inhibitor 1 to the Myocardium Protects the Heart From Ischemia- Reperfusion Injury Through Inhibition of Mitochondria Outer Membrane Permeabilization: A New Therapeutic Modality for Acute Myocardial Infarction. J Am Heart Assoc. 2016; 5 (7): e003872. DOI: 10.1161/JAHA.116.003872.
  17. Kim AS, Miller EJ, Wright TM, Li J, Qi D, Atsina K, et al. A small molecule AMPK activator protects the heart against ischemia-reperfusion injury. J Mol Cell Cardiol. 2011; 51: 24–32.