Skip to main content

Advertisement

SpringerLink
Log in

Dose-dependent effects of perfluorocarbon-based blood substitute on cardiac function in myocardial ischemia–reperfusion injury

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion (PFE) in ex vivo-induced ischemia–reperfusion injury of an isolated rat heart. The first part of the study aimed to determine the dose of 10% perfluoroemulsion (PFE) that would show the best cardioprotective effect in rats on ex vivo-induced ischemia–reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFE, the animals were divided into a control or experimental group. They were also grouped depending on the applied dose (8, 12, 16 ml/kg body weight) of saline or PFE. We observed the huge changes in almost all parameters in the PFE groups in comparison with IR group without any pre-treatment. Calculated in percent, dp/dt max was the most changed parameter in group treated with 8 mg/kg, while the dp/dt min, SLVP, DLVP, HR, and CF were the most changed in group treated with 16 mg/kg 10 h before ischemia. The effects of 10% PFE are more pronounced if there is a longer period of time from application to ischemia, i.e., immediate application of PFE before ischemia (1 h) gave the weakest effects on the change of cardiodynamics of isolated rat heart. Therefore, the future of PFE use is in new indications and application methods, and PFE can also be referred to as antihypoxic and antiischemic blood substitute with mild membranotropic effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

Data are available from the corresponding author upon reasonable request.

Code availability

NA.

References

  1. Spahn D (1999) Blood substitutes artificial oxygen carriers: perfluorocarbon emulsions. Crit Care 5:R93–R97. https://doi.org/10.1186/cc364

    Article  Google Scholar 

  2. Bilenko MV (1989) Ischemic and reperfusion injures of organs molecular mechanisms, ways of preventing and treatment. Medicine, Moscow (in Russian)

    Google Scholar 

  3. Blaisdell FW (1989) The reperfusion syndrome. Microcirc Endothelium Lymphatics 5:127–141

    PubMed  CAS  Google Scholar 

  4. Ar’Rajab A, Dawidson I, Fabia R, (1996) Reperfusion injury. New Horiz 4:224–234

    Google Scholar 

  5. Lindsay TF, Luo XP, Lehotay DC, Rubin BB, Anderson M, Walker PM, Romaschin AD (1999) Ruptured abdominal aortic aneurysm, a “two-hit” ischemia/reperfusion injury: evidence from an analysis of oxidative products. J Vasc Surg 30:219–228. https://doi.org/10.1016/s0741-5214(99)70131-x

    Article  PubMed  CAS  Google Scholar 

  6. Vlasov TD, Smirnov DA, Nutfullina GM (2001) Adaptation of the rat small intestine to ischemia. Ross Fiziol Zh Im I M Sechenova 87:118–124 (in Russian)

    PubMed  CAS  Google Scholar 

  7. Gennaro M, Mohan C, Ascer E (1996) Perfluorocarbon emulsion prevents eicoasanoid release in skeletal muscle ischemia and reperfusion. Cardiovasc Surg 4:399–404. https://doi.org/10.1016/0967-2109(95)00060-7

    Article  PubMed  CAS  Google Scholar 

  8. Memezawa H, Katayama Y, Shimizu J, Suzuki S, Kashiwagi F, Kamiya T, Terashi A (1990) Effects of fluosol-DA on brain edema, energy metabolites, and tissue oxygen content in acute cerebral ischemia. Adv Neurol 52:109–118

    PubMed  CAS  Google Scholar 

  9. Mosca RS, Rohs TJ, Waterford RR, Childs KF, Brunsting LA, Bolling SF (1996) Perfluorocarbon supplementation and postischemic cardiac function. Surgery 120:197–204. https://doi.org/10.1016/s0039-6060(96)80288-1

    Article  PubMed  CAS  Google Scholar 

  10. Kubes P (1993) Ischemia-reperfusion in feline small intestine: a role for nitric oxide. Am J Physiol 264:G143–G149. https://doi.org/10.1152/ajpgi.1993.264.1.G143

    Article  PubMed  CAS  Google Scholar 

  11. Mathy-Hartert M, Krafft MP, Deby C, Deby-Dupont G, Meurisse M, Lamy M, Riess JG (1997) Effects of perfluorocarbon emulsions on cultured human endothelial cells. Artif Cells Blood Substit Immobil Biotechnol 25:563–575. https://doi.org/10.3109/10731199709117453

    Article  PubMed  CAS  Google Scholar 

  12. Speiss BD (2009) Perfluorocarbon emulsions as a promising technology: a review of tissue and vascular gas dynamics. J Appl Physiol 106:1444–1452. https://doi.org/10.1152/japplphysiol.90995.2008

    Article  CAS  Google Scholar 

  13. Cohn C, Cushing M (2009) Oxygen Therapeutics: Perfluorocarbons and Blood Substitute Safety. Crit Care Clin 25:399–414. https://doi.org/10.1016/j.ccc.2008.12.007

    Article  PubMed  CAS  Google Scholar 

  14. Cabrales P, Ingaglietta M (2013) Blood substitutes: evolution from non-carrying to oxygen and gas carrying fluids. ASAIO J 59(4):337–354. https://doi.org/10.1097/MAT.0b013e318291fbaa

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Verdin-Vasquez RC, Zepeda-Perez C, Ferra-Ferrer R, Chavez-Negrete A, Contreras F, Barroso-Aranda J (2006) Use of perftoran emulsion to decrease allogeneic blood transfusion in cardia surgery: clinical trail. Artif Cells Blood SubstitImmobil and Biotechnol 34:433–454. https://doi.org/10.1080/10731190600683969

    Article  CAS  Google Scholar 

  16. Eckmann DM, Lomivorotov VN (2003) Microvascular gas embolization clearance following perfluorocarbon administration. J Appl Physiol 94:860–868. https://doi.org/10.1152/japplphysiol.00719.2002

    Article  PubMed  CAS  Google Scholar 

  17. Mayevskiy EI, Aksenova OG, Bogdanova LA, Moroz VV, Senina RY, Pushkin SY, Ivanitskiy GR (2001) Analysis of clinical and adverse effects during phase I and II clinical studies of perftoran. Russian Blood Banking Bulletin No.4

  18. Maevsky E, Ivanitsky G, Bogdanova L, Axenova O, Karmen N, Zhiburt E, Senina R, Pushkin S, Maslennokov I, Orlov A (2005) Clincial results of perftoran application: present and future. Artif Cells Blood SubstitImmobil and Biotechnol 33:37–46. https://doi.org/10.1081/bio-200046654

    Article  CAS  Google Scholar 

  19. Kozhura VL, Basarab DA, Timkina MI, Golubev AM, Reshetnyak VI, Moroz VV (2005) Reperfusion injury after critical intestinal ischemia and its correction with perfluorochemical emulsion “perfloran.” World J Gastroenterol 11:7084–7090. https://doi.org/10.3748/wjg.v11.i45.7084

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Anthes Anthes E (2015) Evidence-based medicine: save blood, save lives. Nature 520:24–26. https://doi.org/10.1038/520024a

    Article  PubMed  CAS  Google Scholar 

  21. Frustaci A, Kajstura J, Chimenti C et al (2008) Myocardial cell death in human diabetes. Circ Res 87:1123–1132

    Article  Google Scholar 

  22. Abutarboush R, Saha BK, Mullah SH, Arnaud FG, Haque A, Aligbe C, Pappas G, Auker CR, McCarron RM, Moon-Massat PF, Scultetus AH (2016) Cerebral microvascular and systemic effects following intravenous administration of the perfluorocarbon emulsion perftoran. J Funct Biomater 7(4):29. https://doi.org/10.3390/jfb7040029

    Article  PubMed Central  CAS  Google Scholar 

  23. Aimo A, Borrelli C, Giannoni A, Pastormerlo LE, Barison A, Mirizzi G, Emdin M, Passino C (2015) Cardioprotection by remote ischemic conditioning: mechanisms and clinical evidences. World J Cardiol 7:621–632. https://doi.org/10.4330/wjc.v7.i10.621

    Article  PubMed  PubMed Central  Google Scholar 

  24. Bryan NS, Calvert JW, Elrod JW, Gundewar S, Ji SY, Lefer DJ (2007) Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury. Proc Natl Acad Sci USA 104:19144–19149. https://doi.org/10.1073/pnas.0706579104

    Article  PubMed  PubMed Central  Google Scholar 

  25. D’ascenzo F, Cavallero E, Moretti C, Omede P, Sciuto F, Rahman IA, Bonser RS, Yunseok J, Wagner R, Freiberger T, Kunst G, Marber MS, Thielmann M, Ji B, Amr YM, Modena MG, Zoccai GB, Sheiban I, Gaita F (2012) Remote ischaemic preconditioning in coronary artery bypass surgery: a meta-analysis. Heart 98:1267–1271. https://doi.org/10.1136/heartjnl-2011-301551

    Article  PubMed  Google Scholar 

  26. Depre C, Vatner SF (2007) Cardioprotection in stunned and hibernating myocardium. Heart Fail Rev 12:307–317. https://doi.org/10.1007/s10741-007-9040-3

    Article  PubMed  CAS  Google Scholar 

  27. Downey JM (1990) Free radicals and their involvement during long-term myocardial ischemia and reperfusion. Annu Rev Physiol 52:487–504. https://doi.org/10.1146/annurev.ph.52.030190.002415

    Article  PubMed  CAS  Google Scholar 

  28. Endemann DH, Schiffrin EL (2004) Endothelial dysfunction. J Am Soc Nephrol 15:1983–1992. https://doi.org/10.1097/01.ASN.0000132474.50966.DA

    Article  PubMed  CAS  Google Scholar 

  29. Mangoni AA, Sherwood RA, Swift CG, Jackson SH (2002) Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial. J Int Med 252:497–503. https://doi.org/10.1046/j.1365-2796.2002.01059.x

    Article  CAS  Google Scholar 

  30. Lai WK, Kan MY (2015) Homocysteine-induced endothelial dysfunction. Ann Nutri Metab 67:1–12. https://doi.org/10.1159/000437098

    Article  CAS  Google Scholar 

  31. Jacobsen DW (2000) Hyperhomocysteinemia and oxidative stress: time for a reality check? Arterioscler Thromb Vasc Biol 20:1182–1184. https://doi.org/10.1161/01.atv.20.5.1182

    Article  PubMed  CAS  Google Scholar 

  32. Czerska M, Mikołajewska K, Zielinski M, Gromadzinska J, Wasowicz W (2015) Today’s oxidative stress markers. Med Pr. 66:393–405. https://doi.org/10.13075/mp.5893.00137

    Article  PubMed  Google Scholar 

  33. Stoian I, Oros A, Moldoveanu E (1996) Apoptosis and free radicals. Biochem Mol Med 59:93–97. https://doi.org/10.1006/bmme.1996.0072

    Article  PubMed  CAS  Google Scholar 

  34. Djukic M, Ninkovic M, Jovanovic M (2008) Oxidative stress: clinical diagnostic significance. JMB 27:409–425. https://doi.org/10.2478/v10011-008-0024-1

    Article  CAS  Google Scholar 

  35. Halliwell B (1994) Free radicals, antioxidants, and human diseases: curiosity, cause, or consequence? Lancet 344:721–724. https://doi.org/10.1016/s0140-6736(94)92211-x

    Article  PubMed  CAS  Google Scholar 

  36. Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, Dhama K (2014) Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int 2014:761264. https://doi.org/10.1155/2014/761264

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Tak PP, Firestein GS (2001) NF-kappaB: a key role in inflammatory diseases. J Clin Invest 107:7–11. https://doi.org/10.1172/JCI11830

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Hampton MB, Kettle AJ, Winterbourn CC (1998) Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92:3007–3017

    Article  PubMed  CAS  Google Scholar 

  39. Romero MM, Basile JI, Lopez B, Ritacco V, Barrera L, Sasiain Mdel C, Aleman M (2014) Outbreaks of Mycobacterium tuberculosis MDR strains differentially induce neutrophil respiratory burst involving lipid rafts, p38 MAPK and Syk. BMC Infect Dis 14:262. https://doi.org/10.1186/1471-2334-14-262

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, Chock PB, Rhee SG (1997) Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor- mediated tyrosine phosphorylation. J Biol Chem 272:217–221

    Article  PubMed  CAS  Google Scholar 

  41. Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT (1998) Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci USA 95:11715–11720. https://doi.org/10.1073/pnas.95.20.11715

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Chandel NS (2014) Mitochondria as signaling organelles. BMC Biol 12:34. https://doi.org/10.1186/1741-7007-12-34

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Chandel NS, Trzyna WC, McClintock DS, Schumacker PT (2000) Role of oxidants in NF- kappa B activation and TNF-alpha gene transcription induced by hypoxia and endotoxin. J Immunol 165(2):1013–1021. https://doi.org/10.4049/jimmunol.165.2.1013

    Article  PubMed  CAS  Google Scholar 

  44. Valko M, Rhodes CJ, Moncol J, Izakovic M (2006) Free radicals metals and antioxidants in oxidative stress induced cancer. Chem Biol Interact 160:1–40. https://doi.org/10.1016/j.cbi.2005.12.009

    Article  PubMed  CAS  Google Scholar 

  45. Steinberg D (1997) Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272:20963–20966. https://doi.org/10.1074/jbc.272.34.20963

    Article  PubMed  CAS  Google Scholar 

  46. Anavi S, Ni Z, Tirosh O, Fedorova M (2014) Steatosis-induced proteins adducts with lipid peroxidation products and nuclear electrophilic stress in hepatocytes. Redox Biol 4C:158–168. https://doi.org/10.1016/j.redox.2014.12.009

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the Faculty of Medical Sciences, University of Kragujevac.

Funding

NA.

Author information

Authors and Affiliations

  1. Faculty of Medical Sciences, Department of Physiology, University of Kragujevac, Svetozara Markovića 69, 34000, Kragujevac, Serbia

    Vladimir Jakovljevic & Jasmina Sretenovic

  2. Department of Human Pathology, First Moscow State Medical, University IM Sechenov, Trubetskaya Street 8, Str. 2 119991, Moscow, Russian Federation

    Vladimir Jakovljevic, Sergey Vorobyev, Sergey Bolevich, Elena Morozova, Alexander Saltykov, Alexandra Orlova, Tatiana Sinelnikova, Maria Kruglova, Ekaterina Silina & Anastasia Mikhaleva

  3. Department of Pathophysiology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

    Stefani Bolevich, Peter Litvickiy & Alexander Tsymbal

  4. Department of Pharmacology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

    Stefani Bolevich & Vladimir Fisenko

  5. Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

    Isidora Milosavljevic, Jovana Jeremic & Tamara Nikolic Turnic

  6. Department of Statistics and Informatics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

    Vladislava Stojic

  7. N.A.Semashko Public Health and Healthcare Department, F.F. Erismann Institute of Public Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

    Tamara Nikolic Turnic

Authors
  1. Vladimir Jakovljevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sergey Vorobyev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sergey Bolevich
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Morozova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefani Bolevich
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexander Saltykov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter Litvickiy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vladimir Fisenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alexander Tsymbal
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alexandra Orlova
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tatiana Sinelnikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Maria Kruglova
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ekaterina Silina
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Anastasia Mikhaleva
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Isidora Milosavljevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jasmina Sretenovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Vladislava Stojic
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Jovana Jeremic
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Tamara Nikolic Turnic
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

VLJ; SV: Conceptualization, Writing- Original draft preparation; SV; SB; EM; SSB; AS; PL; Validation, Visualization, and Methodology. VF; AT: Methodology. JJ; IS; TNT: Software. AO; TS: Data curation; Visualization. JJ; VLJ: Investigation. MK; ES; AM; TNT: Conceptualization, Writing-Original draft preparation, Supervision, and Writing-Reviewing and Editing.

Corresponding author

Correspondence to Vladimir Jakovljevic.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The study is approved by the Ethics Committee for Laboratory Animal Welfare of the Faculty of Medical Sciences, University of Kragujevac, Serbia.

Consent to participate

NA.

Consent for publication

NA.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jakovljevic, V., Vorobyev, S., Bolevich, S. et al. Dose-dependent effects of perfluorocarbon-based blood substitute on cardiac function in myocardial ischemia–reperfusion injury. Mol Cell Biochem 477, 2773–2786 (2022). https://doi.org/10.1007/s11010-022-04479-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-022-04479-0

Keywords

Search

Navigation