Investigation of the effects of cilostazol on the myocardial ischemia-reperfusion injury of rats.

Anar Amrah 1 *
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1 Republican Diagnostic Center
* Corresponding Author
J CLIN MED KAZ, Volume 21, Issue 2, pp. 59-65.
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Author Contributions: Conceptualization, formal analysis, investigation, methodology, project administration, supervision; validation, visualization, roles/writing – original draft, writing – review and editing, A.A. The author has read and agreed to the published version of the manuscript.


Background. Myocardial ischemia, occurring as a consequence of imbalance between oxygen supply and demand, causes a rapid metabolic and structural
impairment within the tissue. After a period of ischemia, sudden onset of reperfusion causes a transition to aerobic metabolism within living cells. Afterwards, emerging substrates initiate a chain of reactions leading to tissue injury. This situation is called “ischemia reperfusion injury”. Despite all technical advancements in anesthesia, myocardial protection and cardiac surgical techniques, we still face the clinical reflections of ischemia reperfusion (IR) injury.
Materials and methods. The protective effect of cilostasole on IR injury in an animal model of experimental myocardial ischemia and reperfusion was investigated. In this regional myocardial ischemia model, male Wistar-Albino rats were used as subjects and they were allocated into three groups; ischemia (n=8), sham (n=8), and cilostazole (n=8). LAD was occluded for 45 minutes, and then reperfused for three hours. Rats received Cilostazole 20 mg/kg/d by gastric gavage once daily. During IR hemodynamic parameters were recorded. Serum analysis for CK-MB and Troponin T were analysed at 180th minute of ischemia. Ischemic zone was measured by dying with Evans Blue and infarct area was measured by dying with triphenyltetrazolium chloride.
Results. Before the onset of LAD occlusion, as well as at 25th, 60th and 120th minutes of occlusion, all groups were similar in terms of blood pressure and pulse rate.
The total area, affected area and necrotic area were calculated by using formulas; affected area ratio= affected area/total area X 100, necrotic area ratio = necrotic area/total affected area X 100, necrotic area and affected area ratio = necrotic area /affected area X 100.  Affected area and total area ratio was significantly higher in IR group, compared with cilostazole group (t=8.965; p<0.001). Similarly, necrotic area and total area ratio was higher in IR group, compared with cilostazole group (t=8.965; p<0.001). The necrotic area and affected area ratios were similar in IR and cilostazole groups (t=0.245; p=0.810). CK-MB level differences were not statistically significant between two groups (Z=0.382; p=0.721).
Troponin levels were similar between IR and cilostazole groups and the difference was not statistically significant (Z=0.630; p=0.574). Pathological specimens of the heart were scanned for myocytolysis, PMNL and hemorrhage.  The difference between mean value of MDA enzyme levels were statistically significant (p<0.001) between all groups.  MDA enzyme levels, from higher to lower was IR, cilostazole and Sham group.  SOD levels (F=5.910; p=0.009) were significantly lower in Sham group when compared with IR group (p=0.008). The differences between Sham and cilostazole groups and IR and cilostazole gropus were not statistically significant (p=0.008). According to planimetric values and enzyme levels, cilostazole was found to be effective in reducing the ischemic zone, without effecting the necrotic zone in cardiac ischemia reperfusion damage. Therefore cilostazole has protective effects agains ischemia reperfusion damage.

Conclusion. This study explored how cilostazol affects myocardial ischemia-reperfusion injury in rats, finding that cilostazol administration during reperfusion may protect against such injury. Through various analyses, we observed positive outcomes associated with cilostazol treatment, suggesting its potential in reducing myocardial damage. Further research is needed to understand the underlying mechanisms and optimize therapeutic strategies, but our findings highlight cilostazol's promise in improving clinical outcomes in cardiac interventions.


Amrah A. Investigation of the effects of cilostazol on the myocardial ischemia-reperfusion injury of rats.. J CLIN MED KAZ. 2024;21(2):59-65.


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