Gabriel C1*, Ortiz Fragola JP1, Tumarkin M1, Moriondo M1, Angélica M1, Martin S1, Francisco A1, Giuseppe A2 and José M1
1Department of Cardiological Research, University of Buenos Aires, Argentina
2Department of Cardiology, University Hospital of Perugia, Italy
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 production under ischemic conditions by inhibition of free fatty acid oxidation. Kidney and heart function are affected by the HS; we hypothesized that TMZ could be protect these tissues. The objective of the current study is analyzed, by fractal dimension, the early organ damages observed in a HS animal model 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 blood pressure was maintained between 37 mmHg and 42 mmHg for 60 min. After HS, shed blood was reinfused and Ringer lactate was injected over a Resuscitation Period (RP) of 30 min. Arterial blood samples were obtained for baseline and at the end of HS and RP. Animals were sacrificed immediately after RP and samples of kidneys and left ventricle of heart were obtained. Data are expressed as mean ± SD. Statistical comparisons between different groups were made by Student t-test. Histological scores were analyzed by the Mann-Whitney test. A p<0.05 was considered statistically significant. Results: At the end of HSP, compared with Controls, TMZ group showed less increase of serum Cr (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: 13.34 mmol/L ± 3.19 mmol/L; TMZ: 17.08 mmol/L ± 1.50 mmol/L; p=0.045). Fractal Dimension analysis showed 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 damage in kidneys and heart. Thus, TMZ might be a viable adjunct in the treatment of severe hypovolemia.
Hypotension; Ischemia reperfusion injury; Acute kidney injury; Shock therapy; Drug effects
Gabriel C, Ortiz Fragola JP, Tumarkin M, Moriondo M, Angélica M, Martin S, et al. Early Protective Effect of Trimetazidine on Heart, Liver and Kidneys Tissues of Wistar Rats Subjected to Hemorrhagic Shock. The Fractal Dimension Technique Utility. Ann Short Reports. 2021; 4: 1066.