PENGARUH PEMBERIAN PENTOKSIFILIN TERHADAP PERUBAHAN KADAR TUMOR NEKROSIS FAKTOR-ALFA PADA CEDERA REPERFUSI-ISKEMIK TUNGKAI AKUT

Teuku Heriansyah

Abstract


Abstrak. Komplikasi tindakan revaskularisasi pasca suatu periode iskemik semakin penting dalam praktek klinis dewasa ini. Reperfusi pada jaringan iskemik menimbulkan repon inflamasi lokal dan sistemik kompleks yang bermuara pada peningkatan kerusakan jaringan. Banyak bukti ilmiah menunjukkan tumor nekrosis faktor alfa (TNF-α) berperan penting dalam patogenesis cedera reperfusi-iskemik (R-I) di berbagai organ, termasuk otot skelet. Upaya mencegah dan mengatasi progresivitas cedera R-I sampai saat ini belum memperlihatkan hasil yang memuaskan. Salah satu obat yang memberikan harapan untuk mencegah cedera R-I adalah pentoksifilin (PTX) melalui potensi anti inflamasinya. Tujuan penelitian ini adalah untuk membuktikan bahwa pemberian PTX mengurangi cedera R-I pada hewan coba kelinci dengan R-I tungkai akut. Penelitian ini merupakan penelitian eksperimental dengan melakukan tindakan iskemik total tungkai kiri selama 3 jam yang diikuti 3 jam periode reperfusi pada 12 ekor kelinci New Zealand White jantan yang dibagi menjadi 3 kelompok (A, B dan C) secara acak. PTX dengan dosis 40 mg/kg BB yang diikuti dosis rumatan 1 mg/kg BB/jam mulai diberikan 2,5 jam periode iskemik pada kelompok A, sementara cairan garam fisiologis diberikan dengan kecepatan yang sama pada kelompok B. Kelompok C sebagai kontrol negatif. Tindakan R-I dilakukan dengan oklusi dan reperfusi pangkal arteri iliaka komunis sinistra. Kadar TNF-α diperiksa pada 2,5 jam iskemik dan pada 2 jam reperfusi. Pada periode iskemik, didapatkan kadar rerata TNF-α kelompok A 103.66 ± 39.20 pg/ml, rerata kelompok B 149.66 ± 67.23 pg/ml, sementara pada periode reperfusi kadar rerata kelompok A 496.33 ± 97.37 pg/ml dan rerata kelompok B 881.66 ± 164.50 pg/ml. Tidak terdapat perbedaan bermakna kadar rerata TNF-α diantara kedua kelompok pada periode iskemik (p = 0.222). Terjadi peningkatan bermakna kadar rerata TNF-α pada tiap kelompok perlakuan dari periode iskemik ke reperfusi (p = 0.001). Pemberian PTX pada kelompok A mampu menekan secara bermakna peningkatan kadar TNF-α saat reperfusi sebesar 392.66  ± 114 pg/ml dibanding kelompok B (p = 0.015). Disimpulkan bahwa PTX menurunkan kadar TNF-α plasma kelinci dengan cedera R-I tungkai akut.

Abstract. Nowadays, the importance of revascularization complication after an ischemic period in clinical practice has grown. Reperfusion of an ischemic tissue causes complex local and systemic inflammation response leading to increase in tissue damage. Many studies has shown that Tumor Necrosis Factor-α (TNF-α) plays a major role in the pathogenesis of ischemic reperfusion (I-R) injury in various organs, including skeletal muscle. Until now, efforts to prevent and to suppress the progressivity of I-R injury has not been satisfying. One promising drug for the prevention or I-R injury through its anti-inflammatory effect is Pentoxifylline (PTX). Therefore we studied the effect of PTX on I-R injury in rabbits with acute limb I-R marked by TNF-α level. This study was an animal experimental study using twelve male New Zealand White rabbits. The rabbits were divided randomly within 3 groups (A,B, and C). All of the animals experienced total ischemia of the left limb for 3 hours followed by 3 hours of reperfusion period. Group A were given 40 mg/BW PTX followed with 1 mg/BW/Hour maintenance dose. The drug was given after 2.5 hours of ischemia. Rabbits assigned to group B were given normal saline and group C were negative control. I-R were conducted by occluding and reperfusing proximal of the left common iliac artery. Level of TNF-α were measured after 2.5 hours of ischemia and after 2 hours of reperfusion. The mean level of TNF- α in the ischemic period were : 103.66 ±39.20 pg/ml (group A) and 149.66 ±67.23 pg/ml (group B), while in the reperfusion period the mean level of TNF-α were 496.33 ±97.37 pg/ml (group A) and 881.66 ±164.50 pg/ml (group B). There were no significant difference of TNF-α level in both groups in the ischemic period (p = 0,222). Significant increase of the mean TNF-α were seen in both experimental groups from the ischemic to the reperfusion period. PTX in group A significantly suppresses the TNF-α increase while reperfusion as much as 392.66 ±114 pg/ml compared to group B (p = 0.015). It was concluded that  the administration of PTX decreased the TNF-α level in rabbits with acute limb I-R injury.


Keywords


Cedera reperfusi-iskemik tungkai akut; pentoksifilin; TNF-α Acute limb ischemic-reperfusion injury; pentoxifylline; TNF-α

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