Tacrolimus attenuates myocardium damage to the total hepatic ischemia-reperfusion via regulation of the mitochondrial function.
BACKGROUND
Ischemia and reperfusion injury to the liver remains an important clinical problem during liver transplantation and the protection of myocardial function is critical for patients suffering liver transplantation. In the present study, we evaluated the effect of tacrolimus on injured myocardium and mitochondria after total hepatic ischemia-reperfusion (THIR).


METHODS
We utilized the THIR model to mimic the liver transplantation and evaluate the myocardial injury after THIR. Male Wistar rats were divided into four groups: control (sham operated); THIR; THIR+tacrolimus (intraperitoneally, 0.1 mg/kg), and tacrolimus alone group.


RESULTS
THIR indeed damaged the myocardial and mitochondrial function, including increasing the level of MB isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase (LDH), decreasing mitochondrial transmembrane potential (MTP), mitochondrial respiratory and phosphorylating activities (P < 0.05). After administration of tacrolimus, myocardial injuries were significantly attenuated (P < 0.05).


CONCLUSIONS
THIR injury was associated with myocardial injury, perhaps resulting from mitochondrial function alterations. The inhibition of calcineurin and the improvement of mitochondrial respiration and antioxidant capacity maybe contributed to the protection of myocardial mitochondria function after THIR.
First Department of Comprehensive Surgery, South Building, PLA General Hospital of China, Beijing, China.
Yawei
Y
Chen
Xiaohua
X
Xie
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D006335:Heart Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply*; D016031:Liver Transplantation; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology*; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000150:complications*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D007770:L-Lactate Dehydrogenase; D052279:Creatine Kinase, MB Form; D019703:Calcineurin; D000254:Sodium-Potassium-Exchanging ATPase; D016559:Tacrolimus