Hyperbaric oxygenation and statins in the treatment of sepsis in rats

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Budući da efekti primene hiperbarične oksigenacije i statina u sepsi do sada nisu poznati, bilo bi od značaja ispitati kombinaciju navedenog farmakološkog i nefarmakološkog manevra na animalnom modelu sepse. Cilj: Ispitivanje uticaja primene hiperbarične oksigenacije i lekova iz grupe statina, kao i njihove kombinovane upotrebe na biohemijske, oksidacionoinflamacijske i kliničke parametre sepse pacova. Metode: 110 muških pacova je bilo svrstano u kontrolnu i grupe sa indukovanom sepsom: 1. pacovi bez terapije, 2. pacovi na standardnoj antibiotskoj terapiji za gram negativne i anaerobne bakterije (cefuroksim/metronidazol u dozi od 10/3,5 mg/kg/dan i.p.), 3. pacovi na tretmanu HBO, 4. pacovi na standardnoj antibiotskoj terapiji uz HBO tretman, 5. pacovi na tretmanu statinima, 6. pacovi na kombinovanom tretmanu HBO i statinima. Sepsa je izazvana korišćenjem modela fekalnog peritonitisa. U studiji su određivane sledeće varijable: procena težine sepse i stope preživljavanja, biohemijski pokazatelji sepse, biomarkeri oksidacionog stresa i inflamacije, i patohistološke odlike organa. Takođe je ispitivana funkcije srca in vivo i eh vivo. Rezultati: Primena antibiotske terapije kao i njeno udruženo dejstvo sa HBO je bilo povezano sa smanjenim vrednostima svih ispitivanih biohemijskih pokazatelja sepse odnosno remisijom kliničkog toka sepse. U ispitivanom eksperimentalnom modelu sepsa nije uzrokovala promene u funkciji i perfuziji izolovanog srca pacova. Samostalna ili kombinovana primena HBO i antibiotika je bila udružena sa najmanjom produkcijom oksidaciono-inflamacijskih biomarkera. Dobijeni nalazi ukazuju da se opravdanost upotrebe HBO u tretmanu sepse može razmatrati pre svega u sklopu adjuvantnog terapijskog pristupa sa kauzalnom antibiotskom terapijom.

Introduction: Since the effects of administration of hyperbaric oxygenation and statins in the sepsis are not known so far, it would be important to examine the combination of this pharmacological and non-pharmacological maneuver in an animal model of sepsis. Objective: Investigation of the effects of the use of hyperbaric oxygenation and drugs from the group of statins, as well as their combined application on the biochemical, oxidativeinflammatory and clinical parameters of sepsis in rats. Methods: 110 male rats were classified into control and sepsis-induced groups: 1. rats without therapy, 2. rats on standard antibiotic therapy for gram-negative and anaerobic bacteria (cefuroxime / metronidazole in a dose of 10 / 3.5 mg / kg / day ip), 3. rats on HBO treatment, 4. rats on standard antibiotic therapy with HBO treatment, 5. rats on statin treatment, 6. rats on combined HBO and statin treatment. Sepsis was caused using a model of fecal peritonitis. The study identified the following variables: assessment of sepsis severity and survival rate, biochemical indicators of sepsis, biomarkers of oxidative stress and inflammation, and pathohistological features of organs. Cardiac function was also examined in vivo and ex vivo. Results: The use of antibiotic therapy as well as its combined effect with HBO was associated with reduced values of all examined biochemical indicators of sepsis, ie. remission of the clinical course of sepsis. In the examined experimental model, sepsis did not cause changes in the function and perfusion of the isolated rat heart. The independent or combined use of HBO and antibiotics was associated with the lowest production of oxidative-inflammatory biomarkers. The obtained findings indicate that the justification of the use of HBO in the treatment of sepsis can be considered primarily as part of an adjuvant therapeutic approach with causal antibiotic therapy.

sepsa, antibiotici, hiperbarična oksigenacija, statini, pacovi

sepsis, antibiotics, hyperbaric oxygenation, statins, rats

616.94-08:615.33(043.3)

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