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Abstrak :
Pendahuluan: Cedera iskemia reperfusi CI/R merupakan masalah serius yang dihadapi pascahipoksia menyebabkan kerusakan sel yang letaknya berjauhan remote organ injury. Strategi yang digunakan untuk mengurangi kerusakan hepar pascaiskemia adalah melalui penerapan ischemic pre conditioning PI/R dan hiportemia. PI/R telah terbukti mengurangi kerusakan jaringan melalui mekanisme resistensi terhadap iskemia dan kebutuhan energi lebih rendah. Sedangkan hipotermia menghambat laju kematian sel sehingga dapat diterapkan sebagai terapi awal pada tatalaksana trauma dengan tujuan mencegah kerusakan bertambah berat. Penelitian ini bertujuan untuk diketahuinya efek protektif PI/R dan hipotermia terhadap perubahan morfologi jaringan hepar dan peningkatan kadar malondialdehyde MDA sebagai respon stress oksidatif. Metode: Studi eksperimental pada 24 ekor Oryctolagus cuniculus. Kelompok iskemia dilakukan ligasi arteri femoralis komunis dalam pembiusan selama empat jam untuk menginduksi iskemia, kemudian ligasi dibuka dan kelinci dibiarkan beraktivitas selama delapan jam. Pada kelompok PI/R dilakukan ligasi berulang arteri femoralis komunis kanan selama dua menit, dilepaskan tiga menit sebanyak dua siklus, kemudian diligasi selama empat jam. Kelompok hipotermia, dilakukan iskemia disertai membungkus ekstremitas bawah kanan dengan es, suhu antara 31-33oC Kemudian dilakukan laparotomi, dan diambil organ hepar. Pemeriksaan histopatologi hepar dilihat dari 3 zona, sentral, midzonal, perifer. Untuk menilai stress oksidatif jaringan dilakukan pemeriksaan biokimia dengan malondialdehyde MDA. Dilakukan uji statistik terhadap variabel tersebut dengan kemaknaan. Hasil: Pada pemeriksaan histomorfologi terdapat perbedaan perubahan histomorfologi pada sampel kontrol PI/R, dan Hipotermia terhadap iskemia (p<0,05). Derajat kerusakan histomorfologi pada kelompok PI/R lebih rendah dibandingkan kelompok iskemia reperfusi pada semua zona (p sentral = 0,015, p medial = 0,019, p perifer = 0,026). Analisis kadar MDA memperlihatkan terjadi peningkatan pada kelompok iskemia reperfusi menujukkan adanya stress oksidatif. Kadar MDA pada kelompok PI/R dan hipotermia lebih rendah dibandingkan kelompok iskemia.(p = 0,002). Konklusi: Keadaan iskemia reperfusi menyebabkan perubahan histomorfologi dan stres oksidatif sel–sel hepar. PI/R dan hipotermia mempunyai efek protektif pada cedera iskemia reperfusi. Efek protektif PI/R lebih baik dari hipotermia. ...... Introduction: Ischemia-reperfusion injury IRI is a serious problem occuring after hypoxia it causes injuries to cells located remotely from one another remote organ injury. Strategies used to decrease hepatic injuries post ischemic condition are composed as ischemic pre-conditioning IPC and hypothermia management procedures. IPC has been proven to decrease tissue injuries through resistance mechanisms towards ischemia and lower energy requirements. Meanwhile, hypothermia detained the rate of cell deaths, therefore, it can be used as initial therapy on trauma management in order to prevent worsening of the injuries. This research aims to evaluate the protective effects of IPC and hypothermia towards morphological changes of hepatic tissues and the increase of malondialdehyde MDA level as a response to oxidative stress.Methods. Methods: This research is an experimental, descriptive-analytical study on 24 Oryctolagus cuniculus. The specimens were divided into four groups, with one group as control. The ischemia group underwent femoral artery ligations under anesthesia for four hours to induce ischemia. Afterwards, the ligations were released and the rabbits were free to roam for eight hours. The IPC group underwent repeated ligations of right communal femoral artery for two minutes and three minutes of release in two cycles. Afterwards, the arteries were ligated for four hours. The hypothermia group underwent ischemia and wrapping of right lower extremities using ice, with temperature around 31-33oC. Afterwards, laparotomies were conducted on all groups to obtain and evaluate the liver. Hepatic histopathology assessment were conducted from 3 zones, the central, midzone, and peripheral zone. To evaluate the effects of oxidative stress on the tissue, a biochemical assessment with malondialdehyde MDA was conducted. Statistical tests were then conducted to assess the relationship between the variables with significance level p < 0.05. Results: On histomorphological assessment, there were histomorphologic changes on control samples for IPC and hypothermia compared to ischemia p < 0.05. On MDA level analysis, there were increases in all four groups p < 0.05. However, there were no significant differences for the histomorphological changes when compared between central, medial, and peripheral zones. Conclusion: Ischemic reperfusion condition causes histomorphological changes and oxidative stress on hepatic cells. IPC and hypothermia have protective effects from ischemia-reperfusion injuries. The protective effects of IPC was better than hypothermia.

Abstrak :
Latar Belakang : Pasien infark miokard akut dengan elevasi segmen ST IMAEST yang mengalami revaskularisasi dengan intervensi koroner perkutan primer IKPP dapat terjadi cedera reperfusi yang mempengaruhi prognosis. Penelitianpada model hewan menunjukkan ticagrelor melindungi jantung dari cederareperfusi, namun demikian belum ada penelitian pada manusia yang menguji halini. Tujuan : Membandingkan pengaruh antara ticagrelor dengan clopidogrelterhadap cedera reperfusi yang diukur melalui kadar puncak high sensitivetroponin T hs-cTnT pada pasien IMA-EST yang mengalami revaskularisasi. Metode : Penelitian ini merupakan penelitian eksperimental acak tersamar gandayang dilakukan di Rumah Sakit Jantung dan Pembuluh Darah Harapan Kita padabulan Agustus 2016 sampai November 2016. Pasien IMA-EST yang akanmenjalani IKPP dirandomisasi ke dalam dua kelompok yaitu kelompok yangmendapatkan loading ticagrelor 180 mg dilanjutkan dosis rumatan 2x90 mg danyang mendapatkan loading clopidogrel 600 mg dilanjutkan dosis rumatan 1x75mg sebelum IKPP. Dilakukan pemeriksaan hs-cTnT 8 jam pasca dilatasi balonkateter pertama. Hasil Penelitian : Terdapat total 60 subyek, 30 subyek kelompok ticagrelor dan30 subyek kelompok clopidogrel. Tidak ditemukan perbedaan bermakna antaraticagrelor dengan clopidogrel terhadap kadar puncak hs-cTnT 9026 5026 ng/Lvs 9329 4664 ng/L, nilai p 0,809. Kesimpulan : Ticagrelor tidak menyebabkan kadar puncak high sensitivetroponin T yang lebih rendah bila dibandingkan dengan clopidogrel pada pasienIMA-EST yang mengalami revaskularisasi. ......Background : Reperfusion injury influence prognosis in ST elevation myocardialinfarction STEMI patients after primary percutaneous coronary intervention PPCI . Previous study on animal models showed that ticagrelor may haveprotective effect on the heart by reducing reperfusion injury. However, no studyon humans has ever been done to confirm this. Aim : To compare the effect of ticagrelor with clopidogrel on reperfusion injurycalculated by peak high sensitive troponin T hs cTnT in STEMI patients whounderwent revascularization. Methods : This was a randomized controlled trial done in NationalCardiovascular Center Harapan Kita from August 2016 to November 2016.STEMI patients who underwent PPCI was randomized to either ticagrelor loadingdose 180 mg with maintenance of 2x90 mg or clopidogrel loading dose 600 mgwith maintenance of 1x75mg group. Peak hs Troponin T was measured 8 hoursafter first balloon dilatation. Results : Sixty subjects was included in the study, 30 subjects in the ticagrelorgroup and 30 subjects in the clopidogrel group. There were no difference betweenticagrelor vs clopidogrel on peak hs cTnT levels 9026 5026 ng L vs 9329 4664 ng L, p value 0,809. Conclusion : Ticagrelor does not cause a lower peak high sensitive troponin Tlevel compared to clopidogrel in STEMI patients who underwentrevascularization.

Abstrak :
Latar Belakang: Disfungsi mikrovaskular merupakan salah satu manifestasi cedera reperfusi letal. Ticagrelor diketahui memiliki efek kardioprotektif terhadap cedera reperfusi pada hewan coba. Efeknya pada manusia masih harus dibuktikan terutama terhadap perfusi mikrovaskular koroner. Tujuan: Mengetahui efek ticagrelor terhadap perfusi mikrovaskular koroner pada pasien infark miokard akut dengan elevasi segmen ST IMA-EST yang menjalani intervensi koroner perkutan primer IKPP. Metode: Penelitian ini merupakan studi eksperimental acak tersamar ganda yang dilakukan di Rumah Sakit Jantung dan Pembuluh Darah Harapan Kita pada bulan Agustus 2016 sampai November 2016. Pasien IMA-EST yang akan dilakukan IKPP dirandomisasi ke dalam dua kelompok yaitu kelompok yang mendapatkan ticagrelor dan yang mendapatkan clopidogrel sebelum IKPP. Dilakukan pemeriksaan myocardial blush kuantitatif dengan menggunakan program Quantitative Blush Evaluator QuBE. Hasil Penelitian: Terdapat total 40 subyek, 20 subyek kelompok ticagrelor dan 20 subyek kelompok clopidogrel. Tidak ditemukan perbedaan bermakna antara kelompok ticagrelor dengan clopidogrel terhadap nilai myocardial blush kuantitatif dengan QuBE 18,8 6,6-33,6 vs 18,1 12,4-32,3 , nilai p 0,978. Kesimpulan: Tidak terdapat perbedaan nilai myocardial blush kuantitatif pada pemberian ticagrelor sebelum IKPP pada pasien IMA-EST yang menjalani revaskularisasi bila dibandingkan dengan pemberian clopidogrel sebelum IKPP. ......Background: Microvascular dysfunction become one of lethal reperfusion injury manifestation. Ticagrelor known having cardioprotective effect against reperfusion injury in animal trial. It effects in human need further investigation and evidence. Objective: To determine the effect of ticagrelor on coronary microvascular perfusion in acute ST elevation myocardial infarction STEMI patients underwent primary percutaneous coronary intervention PPCI. Method: This was a double blind randomized clinical trial conducted in National Cardiovascular Center Harapan Kita from August to November 2016. Acute ST elevation myocardial infarction patients underwent PPCI were randomized into two groups, ticagrelor or clopidogrel loading dose before PPCI. Quantitative myocardial blush score was assessed after PPCI using Quantitative Blush Evaluator QuBE program. Result: There were 40 subjects included in this trial, 20 subjects in ticagrelor group and 20 subjects in clopidogrel group. There was no significant difference between two groups regarding the QuBE score 18,8 6,6 33,6 vs 18,1 12,4 32,3 , nilai p 0,978. Conclusion: There is no difference on quantitative myocardial blush score in STEMI patient given ticagrelor before PPCI compare to clopidogrel.