Endotelin Reseptör Antagonisti Tezosentanın Sıçanda Lipopolisakkarit İle Oluşturulan Deneysel Sepsis Modelinde Kardiyak Disfonksiyon Üzerine Etkisi

Abstract

KARA, S.C., Effect of Endothelin Receptor Antagonist Tezosentan on Cardiac Dysfunction on an Experimental Model of Sepsis Induced by Lipopolysaccharide in Rats, Hacettepe University Graduate School of Health Sciences, Philosophy of Doctorate (PhD) Thesis in Medical Pharmacology, Ankara, 2019. In this study it is showed that endothelin receptor blocker, tezosentan, ameliorates cardiac dysfunciton caused by septic shock. Tezosentan abrogated reduction of left ventricular developed pressure (72.15 ± 3.67 vs 59.72 ± 1.39), coronary flow rate (11.2 ± 0.54 vs 7.5 ± 0.44), maximum (1586 ± 83.12 vs 1249 ± 36.55) and minimum (-1113 ± 117.90 vs -777.7 ± 35.23) point for derivation of pressure against time of left ventricle, caused by lipopolysaccharide in Langendorff perfused heart. Histopathological examination showed no disruption in myocyte structure or endothelium and no inflamatory cell infiltration. Beating rate was decreased and contraction of isolated atria was not changed. Concentration-response curve of atrial beating rate and atrial contraction with carbachol was similar while there was significant differance between isoprenaline-atrial contraction concentration-response curves of lipopolysaccharide group and control group. Beating rate response of atrium to isoprenaline was similar between two groups. Tezosentan had not effect on dose response curve of atrial beating rate with isoprenaline where as affected atrial contraction response to isoprenaline of both control and lipopolysaccharide groups. Tezosentan increased atrial contraction and beating rate on both control and lipopolysaccharide groups. Lipopolysaccaride did not affect contraction and concentration-response curve of contraction or relaxation curve with isoprenaline and carbachol respectively of papillary muscle. Based on these results tezosentan ameliorated cardiac dysfunction caused by lipopolysaccharide which was not observed in vitro study which can be explained as improving cardiac function in LPS injected rats secondary to its effect on other organ systems.