Trimetazidine improves recovery during reperfusion in isolated rat hearts after prolonged ischemia.
OBJECTIVE
Trimetazidine (TMZ) is a cellular anti-ischemic agent, which has been studied in clinical and experimental investigations, and was shown to have protective affects against myocardial ischemia and reperfusion injury. The major objective of this study was to investigate the cardio-protective effects of trimetazidine in prolonged global ischemia subjected Langendorff perfused rat hearts.


METHODS
Twenty rats (Male Sprague-Dawley) were divided into two study groups. In Group 2 (n=10) TMZ was given by intra-gastric gavage (3 mg/kg BW twice daily for 5 days) prior to operation and was added to the Krebbs-Henseleit perfusate to create a 10-6 M solution to perfuse the isolated rat hearts. Group 1 (n=10) reserved as control group and received saline at the same time period. All hearts were paced at 300 beats/min. After a 20-minute of stabilization period, hearts in both groups were arrested for 120 minutes with crystalloid cardioplegia. After ischemic period, the hearts were then reperfused for 30 minutes. Hemodynamic measurements from left ventricular latex balloon, coronary flow, and creatine kinase (CK-MB) and troponin T (cTnT) levels determined from the coronary effluent were analyzed at the end of stabilization and at every 10-min intervals during reperfusion, and results were compared between two groups.


RESULTS
No significant differences were observed in all entered hemodynamic and biochemical parameters between two groups at the end of the stabilization. However, peak systolic pressure, end diastolic pressure and +dP/dt values reflected improved mechanical myocardial recovery in Group 2 hearts after prolonged ischemia. Besides coronary flow measurements were higher in Group 2 compared with Group 1. CK-MB and cTnT levels indicated to less enzymatic damage in trimetazidine treated hearts during reperfusion.


CONCLUSIONS
In conclusion, both pre-treatment and treatment protocols with TMZ reduce the myocardial damage caused by global ischemia following reperfusion. We could speculate that this beneficial effect of trimetazidine might be useful in open-heart surgery patients, who were subjected to global myocardial ischemia.
Ikizler
Murat
M
Department of Cardiovascular Surgery, Osmangazi University, Medicine Faculty, Eskişehir, Turkey. mikizler@ogu.edu.tr
Dernek
Sadettin
S
Sevin
Behçet
B
Kural
Tuğrul
T
D000284:Administration, Oral; D000818:Animals; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology* / Q000601:surgery*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D014292:Trimetazidine / Q000008:administration & dosage / Q000627:therapeutic use*; D020107:Troponin T / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D020107:Troponin T; D014665:Vasodilator Agents; D003402:Creatine Kinase; D014292:Trimetazidine