Naslov (srp)

Mehanizmi kardiodinamskih i vazoaktivnih efekata propofola kod pacova: značaj oksidativnog stresa, gasotransmitera i kardiovaskularnih biomarkera : doktorska disertacija

Autor

Đurić, Marko, 1989-

Doprinosi

Jakovljević, Vladimir, 1971-
Stevanović, Predrag, 1959-
Palibrk, Ivan, 1964-
Živković, Vladimir, 1984-
Vučković, Sonja, 1963-

Opis (eng)

In this experimental and translational study, it was investigated: a) the effects of acutesystemic anesthetic propofol administration on hematological and standard biochemical parameters,cardiovascular biomarkers, and oxidative stress parameters in hemolysate, coronary effluent andcardiac tissue homogenate, and compared with the effects of acute ketamine or etomidateadministration, b) acute administration of propofol to cardiodynamic characteristics and coronaryflow, and compared with the effects of acute administration of ketamine or etomidate, on theisolated heart, and c) participation of gasotransmitters (NO, H2S and CO), using specific inhibitorsof synthesis or production, as well in the presence of verapamil (calcium channel blocker), all in theeffects of acute administration of propofol on cardiodynamic characteristics, coronary flow,oxidative stress parameters in hemolysate, in cardiac tissue homogenate and in coronary effluent inrats. Material and methods: Male Wistar albino rats (Ratus Norvegicus), 6-8 weeks old andweighing about 200-250 g, were used in the experiments. Experimental animals (total n = 84) weredivided into 6 groups (each group consisted of two subgroups with 7 animals in each subgroup:bolus injection of the anesthetic propofol (1% 10 mg/ml) at a dose of 100 mg / kg b.w.intraperitoneally) (ip.), bolus injection of anesthetic ketamine at a dose of 40 mg/kg b.w. (ip.), bolusinjection of anesthetic etomidate at a dose of 20 mg/kg b.w. (ip.), inhibitor of the enzyme NOsynthase (inhibitor of NO synthesis) Nomega-nitro-L-arginine monomethyl ester (L-NAME) at adose of 60 mg/kg b.w. (ip.) plus bolus injection of propofol (1% 10 mg/ml) at a dose of 100 mg/kgb.w. (ip.), cystathionine gamma lyase (inhibitor of H2S synthesis) DL-propargylglycine (DL-PAG)at a dose of 50 mg/kg bw (ip.) plus bolus injection of propofol (1% 10 mg/ml) at a dose of 100mg/kg b.w. (ip.), inhibitor of the enzyme heme oxygenase subtype 1 (CO synthesis inhibitor) zincprotoporphyrin IX (ZnPPIX) at a dose of 50 μmol/kg b.w. (ip.) plus bolus injection of propofol (1%10 mg/ l) at a dose of 100 mg/kg b.w. (ip.). The subgroups are designed to are in one subgroupevaluated cardiodynamic parameters, coronary flow, oxidative stress in coronary effluent andresponse to verapamil (3 μmol/l for 5 minutes) in an isolated heart (ex vivo), and in the secondsubgroup sampled the blood and cardiac tissue of anesthetized rats for evaluation of biochemicaland hemostatic parameters, as well as oxidative stress in hemolysate and cardiac tissue. Results:Investigation of the effects of gasotransmitter inhibition on hematological and biochemicalparameters, as well as on oxidative stress parameters in hemolysate, after propofol administration,found that propofol has a wide range of non-anesthetic effects, which are variable in relation togastransmitter production status NO, H2S and CO. Investigating the effects of inhibition ofgasotransmitters and calcium ion influx on cardiodynamic variables, oxidative stress parameters incoronary effluent and cardiac tissue homogenate after propofol administration, it was found thatgastransmitters (NO, H2S and CO) and calcium ion influx are involved in different ways in propofoleffects. Investigation of the effects of ketamine and etomidate on biochemical and hematologicalparameters, on oxidative stress parameters in hemolysate, on cardiodynamic variables, oxidativestress parameters in coronary effluent and cardiac tissue homogenate, it was found that ketamineshows stronger antioxidant potential that etomidate which has more favorable effects in terms ofcardiac performance. Conclusions: The results of the study indicate a wider range of non-anestheticeffects of propofol, which are cardioprotective, anti-oxidative and cytoprotective, involvinggasotransmitters and calcium ions, and which differ from the effects of other applied anestheticslike ketamine and etomidate.

Opis (srp)

U ovoj eksperimentalnoj i translacionoj studiji ispitivani su: a) efekti akutne primeneanestetika propofola na hematološke i standardne biohemijske parametre, kardiovaskularnebiomarkere, i parametre oksidativnog stresa u hemolizatu, u koronarnom efluentu i u homogenatutkiva srca, i upoređivani sa efektima akutne primene ketamina ili etomidata, b) efekti akutneprimene propofola na kardiodinamske karakteristike i koronarni protok, i upoređivani sa efektimaakutne primene ketamina ili etomidata, na izolovanom srcu, i c) učešće gasotransmitera (NO, H2S iCO), upotrebom specifičnih inhibitora sinteze ili produkcije, kao i odgovore na inhibicijukalcijumskih kanala verapamilom, u efektima akutne primene propofola na kardiodinamskekarakteristike, koronarni protok, parametre oksidativnog stresa u hemolizatu, u homogenatu tkivasrca i u koronarnom efluentu kod pacova. Materijal i metode: U eksperimentima su korišćenimužjaci pacova soja Wistar albino (Ratus Norvegicus), starosti 6-8 nedelja i telesne mase oko 200-250 g. Eksperimentalne životinje (ukupno n=84) podeljene su u 6 grupa (svaka grupa se sastojalaod dve podgrupe sa 7 životinja u svakoj podgrupi: bolus injekcija anestetika propofola (1% 10mg/ml) u dozi 100 mg/kg t.m. intraperitonealno (ip.), bolus injekcija anestetika ketamina u dozi 40mg/kg t.m. (ip.), bolus injekcija anestetika etomidata u dozi 20 mg/kg t.m. (ip.), inhibitor enzimaNO sintaze (inhibitor sinteze NO) L-NAME (Nomega-nitro-L-arginin monometil estar) u dozi 60mg/kg t.m. (ip.) plus bolus injekcija propofola (1% 10 mg/ml) u dozi 100 mg/kg t.m. (ip.), inhibitorenzima cistationin gama liaze [(inhibitor sinteze H2S) DL-propargilglicin (DL-PAG)] u dozi 50mg/kg t.m. (ip.) plus bolus injekcija propofola (1% 10 mg/ml) u dozi 100 mg/kg t.m. (ip.), inhibitorenzima hem oksigenaze subtip 1 (inhibitor sinteze CO) zink protoporfirin IX (ZnPPIX) u dozi 50μmol/kg t.m. (ip.) plus bolus injekcija propofola (1% 10 mg/ml) u dozi 100 mg/kg t.m. (ip.).Podgrupe su koncipirane tako, da su se u jednoj podgrupi procenjivali kardiodinamski parametri,koronarni protok, oksidativni stres u koronarnom efluentu i odgovor na verapamil (3 μmol/l utrajanju od 5 minuta) u izolovanom srcu (ex vivo), a u drugoj podgrupi uzorkovala krv i tkivo srcaanestetisanih pacova za procenu biohemijskih i hemostatskih parametara, kao i oksidativnog stresau hemolizatu i tkivu srca. Rezultati: Ispitivanjem efekata inhibicije gasnih transmitera nahematološke i biohemijske parametre, kao i na parametre oksidativnog stresa u hemolizatu, posleprimene propofola, utvrđeno je da propofol poseduje široki spektar ne-anestetskih efekata, koji supromenljivi u odnosu na status produkcije gasnih transmitera NO, H2S i CO. Ispitivanjem efekatainhibicije gasnih transmitera i influksa jona kalcijuma na kardiodinamske varijable, parametreoksidativnog stresa u koronarnom efluentu i homogenatu tkiva srca, posle primene propofola,utvrđeno je da su gasni transmiteri (NO, H2S i CO) i influks jona kalcijuma uključeni na različitenačine u efekte propofola. Ispitivanjem efekata ketamina i etomidata, na biohemijske i hematološkeparametre, na parametre oksidativnog stresa u hemolizatu, na kardiodinamske varijable, parametreoksidativnog stresa u koronarnom efluentu i homogenatu tkiva srca, utvrđeno je da ketaminpokazuje snažniji anti-oksidativni potencijal u poređenju sa etomidatom, a da etomidat imapovoljnije efekte u pogledu srčanih performansi. Zaključci: Rezultati istraživanja ukazuju na širispektar ne-anestetskih efekata propofola, koji su kardioprotektivni, anti-oksidativni icitoprotektivni, u kojima učestvuju gasotransmiteri i joni kalcijuma, i koji se razlikuju od efekatadrugih primenjenih anestetika ketamina i etomidata.

Opis (srp)

Medicina (anesteziologija sa reanimatologijom, kardiovaskularna istraživanja) - Fiziološke nauke / Medicine (anesthesiology with resuscitation, cardiovascular research) - Physiological sciences Datum odbrane: 01.07.2022.

Jezik

srpski

Datum

2022

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 3.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 3.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode

Predmet

anesthetics, biomarkers, gasotransmitters, oxidative stress, rat, propofol

anestetici, biomarkeri, gasotransmiteri, oksidativni stres, pacov, propofol

616.1-089.5(043.3)