Early Protective Effect of Trimetazidine on Heart, Liver and Kidneys tissues of Wistar Rats Subjected to Hemerrhagic Shock.The Fractal Dimension Technique Utility

Abstract

Introduction: Hemorrhagic Shock (HS) is a condition of reduced tissue perfusion. Trimetazidine(TMZ) is an antianginal drug that promotes a more efficient glucose oxidation and ATP productionunder ischemic conditions by inhibition of free fatty acid oxidation. Kidney and heart function areaffected by the HS; we hypothesized that TMZ could be protect these tissues. The objective of thecurrent study is analyzed, by fractal dimension, the early organ damages observed in a HS animalmodel and the eventually protective effect after TMZ administration.Material and Methods: Wistar rats were randomly divided into 2 groups: Control (n=6) and TMZ(n=7) and submitted to HS. Shock was induced by controlled arterial bleeding; mean arterial bloodpressure was maintained between 37 mmHg and 42 mmHg for 60 min. After HS, shed blood wasreinfused and Ringer lactate was injected over a Resuscitation Period (RP) of 30 min. Arterialblood samples were obtained for baseline and at the end of HS and RP. Animals were sacrificedimmediately after RP and samples of kidneys and left ventricle of heart were obtained. Data areexpressed as mean ± SD. Statistical comparisons between different groups were made by Studentt-test. Histological scores were analyzed by the Mann-Whitney test. A p<0.05 was consideredstatistically significant.Results: At the end of HSP, compared with Controls, TMZ group showed less increase of serumCr (Control: 0.77 ± 0.08 mg/dl; TMZ: 0.64 ± 0.05 mg/dl; p=0.011), lactate (Control: 7.88 mmol/L ±1.39 mmol/L; TMZ: 5.58 mmol/L ± 1.11 mmol/L, p=0.020) and higher bicarbonate (Control: 13.34mmol/L ± 3.19 mmol/L; TMZ: 17.08 mmol/L ± 1.50 mmol/L; p=0.045). Fractal Dimension analysisshowed TMZ protection in heart (FD: Control: 1.732 ± 0.041; TMZ: 1.759 ± 0.043; p<0.0001 and L:Control: 0.33 ± 0.075; TMZ: 0.29 ± 0.066; p=0.01), liver (FD: Control: 1.776 ± 0.039; TMZ: 1.786 ±0.037; p=0.0021 and L: Control: 0.28 ± 0.057; TMZ: 0.29 ± 0.058; p=ns) and kidneys (FD: Control:1.742 ± 0.040; TMZ: 1.796 ± 0.042; p<0.0001 and L: Control: 0.33 ± 0.075; TMZ: 0.29 ± 0.066;p=0.01)Conclusion: In an experimental model of HS, TMZ administration attenuated cell and tissue damagein kidneys and heart. Thus, TMZ might be a viable adjunct in the treatment of severe hypovolemia.