Pathologic investigation of tacrolimus(FK506) on the myokardial ischemia reperfusion injury of rats

Myocardial ischemia, appearing as the consequence of imbalance betweenoxygen supply and demand, causes a rapid metabolic and structural impairmentwithin the tissue. After ischemic period, sudden onset of reperfusion causes atransition to the aerobic metabolism within the living cells. Emerging substratesinitiate a chain of reactions leading to tissue injury. This situation is called ?ischemiareperfusion injury?. Despite all the technical advances in anesthesia, myocardialprotection and cardiac surgical techniques, we still face the clinical reflections ofischemia reperfusion (I/R) injury.Molecular background of the I/R injury is a bit complicated. As it was shownpreviously, free oxygen radicals, excessive intracellular calcium deposition and acascade of inflammatory responses - particularly neutrophils ? are the possiblemechanisms.The protective effect of tacrolimus on I/R injury in an animal model ofexperimental myocardial ischemia and reperfusion was investigated. In the regionalmyocardial ischemia model LAD was occluded for 45 minutes and then reperfusedfor three hours. Male Wistar-Albino rats were used as subjects and were allocatedinto four groups: ischemia (n=4), sham (n=4), control (n=7), and tacrolimus (n=7).Tacrolimus was administered via jugular vein at the dose of 100 ?g.kg-1 during thefirst 15 minutes of reperfusion. Haemodynamic parameters were recorded. CK-MBwas measured at the onset and at the 45th minutes of ischemia and at the 60th and180th minutes of reperfusion as a biochemical parameter. Myocardial infarct area wasmeasured using triphenyltetrazolium chloride (TTC) staining technique.No statistical significance was observed among all groups in haemodynamicparameters recorded at the onset and the 45th minute of ischemia. Systolic arterialpressure was increased in the tacrolimus group (85 mmHg) when compared withsham and control groups at the 60th minute of reperfusion. A statistical significancewas observed (p=0.004). Heart rate was decreased in the tacrolimus group (224bpm) when compared with sham and control groups at the 60th minute of reperfusion.A statistical significance was observed (p=0.047).Mean infarct area/whole area ratio in cross-sections K1=0.182(p=0.025),K2=0.212(p=0.018), K3=0.264(p=0.013), K4=0.227(p=0.015) were lower in thetacrolimus group than the control group. A statistical significance was observed.PNL infiltration degree was 1.6 in the control group and 0.7 in tacrolimusgroup. A statistical significance was observed between the two groups (p=0.045).When the data were observed, infarct area/whole area ratio and PNLinfiltration degree were lower in the tacrolimus group. This indicates that tacrolimusmay have a preventive effect in myocardial ischemia reperfusion injury.Key Words: Tacrolimus, Myocard, İschemia reperfusion injury.