Tesis

Efek Ischemic Reperfusion Injury (IRI) pada Otak: Studi Eksperimental pada Oryctolagus cuniculus = The Effect of Ischemia-Reperfusion Injury on the Brain: An Experimental Study in Oryctolagus cuniculus.

Latar belakang: Ischemic reperfusion injury (IRI) merupakan komplikasi penting pada prosedur bedah kardiovaskular yang melibatkan gangguan aliran darah, termasuk cardiopulmonary bypass. Reperfusi setelah iskemia memicu stres oksidatif dan respons inflamasi sistemik yang dapat menyebabkan kerusakan organ jauh, terutama otak. Strategi proteksi jaringan seperti ischemic pre-conditioning (IPC) dan ischemic postconditioning (IPostC) telah dikembangkan, namun efektivitas relatif dan manfaat kombinasi keduanya terhadap kerusakan otak masih belum jelas. Tujuan: Menilai dan membandingkan derajat kerusakan otak akibat IRI pada model hewan yang diberikan perlakuan iskemik distal saja, ischemic pre-conditioning (IPC), ischemic post-conditioning (IPostC), serta kombinasi ischemic pre- dan postconditioning. Metode: Penelitian ini merupakan studi eksperimental tersamar pada 24 ekor kelinci jantan Oryctolagus cuniculus yang dibagi menjadi empat kelompok. Iskemia diinduksi melalui ligasi arteri iliaca communis selama empat jam, diikuti reperfusi. Perlakuan IPC dan/atau IPostC diberikan sesuai kelompok. Delapan jam pascareperfusi, jaringan otak lobus frontal diambil untuk pemeriksaan histopatologi serta analisis penanda biokimia stres oksidatif dan kerusakan neuron, yaitu malondialdehyde (MDA), S100B, dan 8- hydroxy-2’-deoxyguanosine (8-OHdG). Analisis statistik dilakukan menggunakan uji parametrik atau nonparametrik sesuai distribusi data. Hasil: Kelompok iskemik distal menunjukkan kerusakan otak signifikan secara histopatologis dan biokimia. IPC dan IPostC menurunkan derajat kerusakan dibandingkan kontrol. Kombinasi IPC dan IPostC memberikan efek proteksi paling optimal dengan penurunan signifikan persentase kerusakan neuron serta kadar penanda biokimia. Kesimpulan: IRI menyebabkan kerusakan otak yang bermakna. Kombinasi ischemic pre-conditioning dan post-conditioning memberikan efek neuroprotektif terbaik dan berpotensi diaplikasikan sebagai strategi proteksi otak dalam praktik bedah kardiovaskular.
Kata kunci: IRI; ischemic preconditioning; ischemic postconditioning; kerusakan otak; stress oksidatif


Background: Ischemia-reperfusion injury (IRI) is a major complication in cardiovascular surgical procedures involving transient interruption of blood flow, including cardiopulmonary bypass. Reperfusion following ischemia triggers oxidative stress and systemic inflammatory responses, leading to remote organ injury, particularly in the brain. Tissue-protective strategies such as ischemic preconditioning (IPC) and ischemic postconditioning (IPostC) have been proposed; however, their comparative effectiveness and potential synergistic effects on cerebral injury remain unclear. Objective: To evaluate and compare the extent of cerebral injury caused by ischemiareperfusion injury in an experimental animal model subjected to distal ischemia alone, ischemic preconditioning, ischemic postconditioning, and combined pre- and postconditioning. Methods: This blinded experimental study included 24 male Oryctolagus cuniculus randomly allocated into four groups. Ischemia was induced by common iliac artery ligation for four hours, followed by reperfusion. IPC and/or IPostC protocols were applied according to group allocation. Eight hours after reperfusion, frontal lobe brain tissue was harvested for histopathological examination and biochemical analysis of oxidative stress and neuronal injury markers, including malondialdehyde (MDA), S100B, and 8-hydroxy- 2’-deoxyguanosine (8-OHdG). Statistical analyses were performed using parametric or non-parametric tests as appropriate. Results: The distal ischemia-only group demonstrated significant cerebral injury based on histopathological findings and elevated biochemical markers. Both IPC and IPostC significantly reduced the degree of brain injury compared to controls. The combined IPC– IPostC group exhibited the greatest neuroprotective effect, with the lowest neuronal damage percentage and biomarker levels. Conclusion: Ischemia-reperfusion injury induces significant cerebral damage. Combined ischemic preconditioning and postconditioning provides superior neuroprotection and may represent a promising strategy for cerebral protection in cardiovascular surgical practice.
Keywords: ischemia-reperfusion injury; ischemic preconditioning; ischemic postconditioning; cerebral injury; oxidative stress.