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"Latar Belakang. Cedera Reperfusi Iskemia merupakan eksaserbasi paradoks mengakibatkan disfungsi dan kematian sel setelah aliran darah direstorasi ke jaringan yang sebelumnya iskemia. Pada iskemia tungkai akut, reperfusi menimbulkan reaksi kompleks melibatkan inflamasi lokal maupun sistemik dengan dampak lokal sindroma kompartemen dan dampak sistemik berupa disfungsi hingga kegagalan multi organ. Platelets activating factors (PAF) sebagai mediator inflamasi pospholipid mempunyai efek fisiologis yang poten dan beragam, sehingga meningkatkan respon inflamasi pada cedera reperfusi iskemik.Berbagai upaya untuk mencegah dan memperingan cedera reperfusi iskemik, antara lain penggunaan prosedur ischemic preconditioning, antioksidan dan terapi anti-sitokin telah diteliti namun hasil dan manfaat klinisnya belum memuaskan. PTX, phosphodiesterase nonspesifik derivat xanthine, memperlihatkan efek penekanan inflamasi dan menghambat interaksi lekositendotel yang menjanjikan dalam mencegah cedera reperfusi. Namun hasil penelitian mengenai peran pentoxifylinne dalam menekan reaksi inflamasi melalui penekanan PAF pada iskemia tungkai akut tidak konsisten. Sehingga penelitian ini bertujuan untuk menilai peran PTX dalam mengurangi cedera reperfusi melalui penekanan mediator inflamasi PAF pada hewan coba kelinci dengan Reperfusi Iskemia tungkai akut.Metodologi. Dilakukan tindakan iskemik tungkai kiri selama 3 jam yang diikuti 2 jam periode reperfusi pada 10 ekor kelinci New Zealand White jantan yang dibagi menjadi 2 kelompok (kelompok pentoksifin dan kelompok kontrol) secara acak. Pada kelompok perlakuan diberikan PTX 30 menit sebelum reperfusi dengan dosis initial bolus 40 mg/kgBB diikuti dengan dosis rumatan 1 mg/kg BB/jam hingga 3 jam periode reperfusi. Pada kelompok kontrol diberikan cairan garam fisiologis dengan kecepatan dan volume yang sebanding. Tindakan Iskemik dilakukan dengan oklusi arteri iliaka komunis sinistra mengunakan klem selama 3 jam kemudian dilanjutkan dengan restorasi aliran darah. Pengambialn sampel untuk pemeriksaan kadar PAF dilakukan pada 2,5 jam iskemik dan pada 2 jam reperfusi.Hasil. Pada periode Iskemik dua jam tiga puluh menit tidak mengakibatkan perbedaan bermakna (p=0,754), kadar rerata PAF pada kelompok PTX 13,09 ± 0,41 pg/mL dan kelompok kontrol I3,38 ± 0,28 pg/mL. Pada jam ke dua tindakan reperfusi ditemukan perbedaan bermakna (p=0,009) kadar rerata PAF dari kelompok PTX menurun menjadi 11,36±0,78 pg/mL dan kelompok kontrol meningkat menjadi 25,5±0,78 pg/dL.Kesimpulan. PTX menurunkan kadar PAF plasma kelinci dengan cedera reperfusi iskemikia tungkai akut.

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Background. Ischemic reperfusion injury is a paradoxical exacerbation of cell dysfunction and death following the restoration of blood flow to previously ischemic tissue. Restoration of blood flow is essential to salvage ischemic tissue, however reperfusion itself paradoxically causes further damage to the ischemic tissue, threatening function and viability both organ local and distal through the inflammation response.

In Acute limb ischemia, there are essentially two components: a local component that can result in increasing the regional damage from ischemia inflammatory responses which may result in local syndrome, compartment syndrome, and systemic syndrome, multi organ dysfunction and failure.

Several method and attempt had been studied and performed to prevent and attenuate reperfusion injury such as, ischemic preconditioning, antioxidant, and anti-cytokine therapy, but their clinical benefit were not satisfactory. Pentoxifylline has emerged as an agent that may attenuate inflammation response through several mechanisms. However, studies on PTX and its function to prevent and attenuate inflammation response through attenuating PAF in acute limb ischemic were not consistent. In this study the role of PTX and its function to prevent and attenuate inflammation response through attenuating PAF in acute limb ischemic was investigated.

Methods. Acute limb ischemia in the left lower limbs of 10 New Zealand White male rabbit were performed for 3 hour followed by 2 hours period of ischemia. The rabbits were randomly separated into 2 groups of five (group pentoxifylinne and group control). The Pentoxifylline group was given PTX 40 mg/kg bolus half an hour prior to reperfusion followed by maintenance dose 1 mg/kg/hour until 2 hour post reperfusion, while the control group was given normal saline solution with comparable volume and rate administration. Acute limb Ischemic procedure was performed by direct occlusion of the left femoral artery using non traumatic clamp and followed by releasing the clamp after 3 hours of occlusion. Level of PAF were measured after 2.5 hour of ischemic period and after 2 hours of reperfusion period.

Results. After 2.5 hours of ischemic period, the mean PAF levels did not show any significant difference (p=0.754). The mean PAF level of pentoxifylline group 13.09f0.41 pg/mL, while the mean PAF level of control group 13.38±0.28 pg/mL, After 2 hours period of reperfusion, there were significant differences of mean PAF level between the two groups (p=0.009). The mean PAF level in the control group increase by 12.1 110.79 to became 25.5±0.78 pg/dL, while the mean PAF level of the PTX group decrease by 1.73f1.1 pg/mL and became 11.36±0.78 pg/m L.

Conclusion. PTX decreased the PAF level in rabbits with acute limb ischemic reperfusion injury."

"Latar Belakang. Komplikasi tindakan revaskularisasi pasca suatu periode iskemik mulai menjadi perhatian kalangan medis sejak awal abad ke-20. iskemik tungkai akut merupakan masalah kegawatan kardiovaskular dan tindakan reperfusi terhadap jaringan yang iskemik ternyata sexing memperburuk cedera jaringan yang ada, bahkan sampai dilakukan amputasi. Pada ceders reperfusi iskemik (R-1) terjadi perubahan sifat hemoreologi darah (hematokrit, viskositas, dan deformitas set darah merah). Pentoksifilin (PTXF) mempunyai kemampuan memperbaiki cedera reperfusi dengan meningkatkan aliran darah perifer, memperbaiki deformitas sel darah merah, menurunkan viskositas darah, dan menekan agregasi platelet.Tujuan Penelitian. Untuk mengetahui pengaruh pemberian PTXF terhadap faktor hemoreologi darah pada cedera R-I tungkai akut.Metode. Penelitian dilakukan pada kelinci jantan ras New Zealand White Rabbit (NZW) yang berasal dari 1 galur sebanyak 10 ekor usia 5 bulan dengan berat badan rata-rata 2,5-3 kg. Kemudian hewan coba dibagi dalam 2 kelompok, yakni 5 ekor kelinci kelompok perlakuan diberi PTXF dengan dosis 40 mglkgBB yang diikuti dosis rumatan 1 mglkgBBljam dan 5 ekor kelinci sebagai kontrol diberi cairan NaCl 0,9% dengan kecepatan yang sama seperti kelompok perlakuan. Dilakukan oklusi arteri iliaka komunis sinistra dan setelah 2,5 jam iskemik diambil darah untuk pemeriksaan hematokrit dan viskositas, setelah itu segera diberikan PTXF. Pada jam ke-3 dilakukan reperfusi (membuka oklusi) dan 2 jam setelah reperfusi diambil darah untuk pemeriksaan hematokrit dan viskositas. Data hasil pemeriksaan dianalisis dengan statistik program SPSS 13 dengan menggunakan uji parametrik General Linear Model (GLM) untuk pengukuran berulang.Hasil. Nilai rerata hematokrit kelompok PTXF fase iskemik 37,06+3,88% dan fase reperfusi 34,20+1,90% dengan delta penurunan 2,86%. Nilai rerata hematokrit kelompok nonPTXF fase iskemik 35,88+5,31% dan fase reperfusi 32,90+4,61% dengan delta penurunan 2,98%. Antara pengukuran pertama dan kedua, baik kelompok PTXF dan nonPTXF tidak terdapat perbedaan bermakna (per, i 9 dan p=0,37). Analisis statistik nilai rerata hematokrit antara kelompok PTXF dan nonPTXF tidak terdapat perbedaan bermakna (p=0,74).Nilai rerata viskositas kelompok PTXF fase iskemik 5,25+0,77 ep dan fase referfusi 4,69+0,70 cp dengan delta penurunan 0,558 cp. Nilai rerata viskositas kelompok nonPTXF fase iskemik 4,54+0,48 cp dan fase reperfusi 4,48+1,31 cp dengan delta penurunan 0,066 cp. Antara pengukuran pertama dan kedua, baik, kelompok PTXF dan nonPTXF tidak terdapat perbedaan bermakna secara statistik (p~,26 dan p=0,92). Analisis statistik pada nilai rerata viskositas antara kelompok PTXF dan nonPTXF tidak terdapat perbedaan bermakna (p=0,53).Kesimpulan. Pemberian PTXF pada kelompok perlakuan memperlihatkan hasil tidak bermakna dalam menurunkan nilai hematokrit dan viskositas darah dibanding kelompok kontrol pads keadaan ceders R-I tungkai akut.

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Background: Complications of revascularization after an ischemic period has attract attention from clinicians since the beginning of 20th century. Acute limb ischemia is an emergency cardiovascular problem and revascularization procedures of ischemic tissue has been documented to worsen tissue damage to the extend of a need for limb amputation. In ischemic reperfusion injury, changes in blood hemorheology occurs (hematocrit, viscosity and eryhtrocyte deformities). Pentoxifylline (PTXF) has the ability to repair reperfusion injury by increasing peripheral blood flow, repairing eryhtrocyte deformities, decreasing blood viscosity dan suppressing platelet agregation.Objectives: To investigate the effect of pentoxifylline administration toward hemorheology changes in acute limb ischemic reperfusion injury.Methods: We studied 10 pure strain New Zealand White Rabbit (NZW) age 5 months with mean weight of 2.5-3 kg. The subjects were divided in two groups; 5 of the experimental rabbit were given PTXF 40 mg/kg body weight followed by a maintenance dose of 1 mg/kg body weight/hour, while subjects in the control group received a similar administration of NaCl 0.9%. We performed occlusion of the left common iliac artery and after an ischemic period of 2.5 hours blood samples were taken for hematocrit and viscosity measurement. PTXF were given soon afterward. On the third hour the artery occlusion were opened and after another two hours blood samples were again taken for hematocrit and viscosity measurement. Data analysis were performed by SPSS 13, using parametric test with general linear model (GLM) for repeated measurements.Results: The mean hematocrit value for the PTXF group in the ischemic period were 37.0613.88%, and in the reperfusion period were 34.2011.90%, with a decrease of 2.86%. The mean hematocrit value for the control group in the ischemic and reperfusion period were 35.8815.31% and 32.90±4.61% , respectively, with a decrease of 2.98%. There were no significant difference between the first and second hematocrit measurements both in the experimental and control group (p-0.19 and p=0.37). Statistical analysis of mean hematocrit value between the two groups also showed no significant difference (p=0.74).The mean viscosity value for the PTXF group in the ischemic period were 5.2510.77 cp and in the reperfusion period were 4.6910.70 cp with a difference of 0.558 cp. The mean viscosity value for the control group in the ischemic and reperfusion period were 4.54±0.8 cp and 4.4811.31 cp, respectively, with a decrease of 0.066 cp. There were no statistically significant difference between the first and second viscosity measurements both in the experimental and control group (p=0.26 and p=0.92). Statistical analysis of mean viscosity value between the two groups also showed no significant difference (p=0.53).Conclusion: PTXF administration in the experimentally induced acute limb ischemic reperfusion injury in rabbits have no benefits to decrease hematocrit and viscosity values compared to control group."

"Latar belakang: Pentoksifilin belum memberikan hasil yang konsisten pada pasien stroke iskemik akut sehingga pada penelitian ini dipakai suatu penanda spesifik untuk melihat efektifitas terapi yaitu adanya hiperviskositas darah. Metode: Penelitian ini merupakan penelitian uji klinis acak tersamar tunggal. Pasien stroke iskemik akut onset kurang dari 72 jam yang mengalami hiperviskositas darah diacak menjadi kelompok perlakuan n=22 dan kontrol n=22 . Terapi standar stroke akut diberikan pada semua subyek. Kelompok perlakuan mendapat terapi tambahan berupa pentoksifilin 1.200mg/hari intravena selama lima hari dan dilanjutkan dosis oral 2x400mg per hari selama 23 hari setelahnya. Pemeriksaan viskositas darah dan interleukin-6 dilakukan pada hari pertama dan ketujuh perawatan. Luaran klinis dinilai dengan menggunakan national institute of health stroke scale NIHSS , modified rankin score mRS dan indeks barthel pada hari ketujuh dan juga pada hari ke-30. Hasil: Kadar viskositas darah seluruh subyek mengalami penurunan pada hari ketujuh dan ketiga puluh. Pada kelompok perlakuan, rerata penurunan viskositas darah memiliki perbedaan bermakna pada subyek dengan faktor risiko merokok dan dislipidemia. Tidak didapatkan penurunan kadar interleukin-6 pada kedua kelompok. Kelompok perlakuan memiliki perbaikan defisit neurologis sebesar 32 risiko relatif [RR]1,00; 95 interval kepercayaan [IK] 0,421-3,556; p = 1,00 . Disabilitas dan kemandirian fungsional yang baik didapatkan pada 67 kelompok perlakuan RR 1,026; 95 IK 0,656-1,605; p = 0,9 . Pada kelompok perlakuan, luaran klinis berbeda bermakna pada subyek yang memiliki sakit jantung dan diabetes melitus. Kesimpulan: Setelah pemberian pentoksifilin didapatkan penurunan kadar viskositas dan perbaikan luaran klinis. Studi lanjutan dibutuhkan dengan kriteria yang lebih spesifik dan jumlah sampel yang lebih besar.

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Background: The role of pentoxifylline in acute ischemic stroke lacks objective markers of its efficacy. Therefore, we used blood viscosity to determine the efficacy of pentoxifylline.

Method: This was a randomized single blind, controlled trial. Acute ischemic stroke patients with blood hyperviscosity within 3 day onset were randomly allocated to the study n 22 or control n 22 group. All subjects received a standard treatment for acute ischemic stroke. The study group was administered with intravenous pentoxifylline 1,200 mg day for five consecutive days and continued with oral 800 mg in two divided doses for next twenty three days. Blood viscosity and interleukin 6 IL 6 were evaluated at the first and seventh day. Clinical outcomes were measured using the National Institutes of Health Stroke Scale NIHSS, modified Rankin Scale mRS, and barthel index BI at the seventh and thirtieth day.

Result: The level of blood viscosity of all subjects tends to be decreased on the seventh and thirtieth day. In study group, the decrement of blood viscosity was significant for smoking and dyslipidemic subject. There was no decrement of the IL 6 on both group. The improvement of NIHSS in study group was 32 relative risk RR 1,00 95 CI 0,421 3,556 p 1,00 . At 1 month follow up, 67 of study group had a good functional outcome RR 1,026 95 CI 0,656 1,605 p 0,9 and the good functional outcome was statistically significant for diabetes mellitus and heart disease subject.

Conclusion The decrement of blood viscosity and the improvement of clinical outcome were seen after pentoxifylline administration. "

"Latar Belakang. Cedera Reperfusi-iskemik merupakan isu klinis yang penting dan umum. Hal tersebut dapat terjadi pada trombo-embolisme, penyakit vaskuler aterosklerotik, bedah kardiovaskuler, transplantasi organ, replantasi tungkai dll. Reperfusi jaringan yang iskemik bukan hanya menyebabkan reaksi iniamasi lokal tetapi juga mempengaruhi fungsi organ lain melalui respons inflamasi sistemik. Banyak studi menunjukkan sel polimorfonuklear terutama netrofil mempunyai peranan cedera yang panting dalam proses reperfusi-iskemik dengan menginfiltrasi jaringan iskemik dan juga kedalam organ yang jauh seperti hati, pare, ginjal dsb. Banyak obat yang sudah dicoba untuk untuk mengurangi efek cedera reperfusi dengan basil yang bervariasi. Salah satu obat yang menjanjikan dapat mengurangi cedera reperfusi melalui efek antiinflamasinya adalah Pentoksifilin (PTX). Pada studi eksperimental, kami mengamati efek pemberian PTX terhadap infiltrasi netrofil pada jaringan otot skeletal, hati dan pare hewan kelinci yang dibuat iskemik secara akut pada tungkai bawah dan diikuti dengan reperfusi.Metoda. Dua belas ekor kelinci jantan ras New Zealand White dibagi secara acak menjadi 3 grup (A,B dan C). Grup A diberikan PTX ( n=5); Group B diberikan NaCl 0.9% sebagai kontrol (n=5); Grup C adalah kontrol negatif (n=2). Grup A dan B mengalami total iskemia selama 3 jam pada tungkai bawah dengan Cara menjepit arteri iliaca komunis sinistra dengan klem. Dosis PTX adalah 40 mg/ kgBB bolus diikuti lmglkgBB sebagai dosis rumatan. PTX diberikan 30 menit sebelum reperfusi. Grup B diberikan NaCl 0.9 % dan pada grup C tidak dilakukan tindakan iskemia. Potongan jaringan histopatologi dari otot yang iakemik, hati dan pare diambil pada akhir percobaan (3jam setelah rep erfusi) sebelum dilakukan etanasia.Hasil. Jumlah rerata netrofil pada jaringan otot skeletal, hati dan pare berturut-turut adalah sebagai berikut : Pada grup C adalah 0.67 ± 0.75; 2.00 ± 1.41 dan 4.33 ± 1.49. GrupA adalah 3.53 ± 6.01; 7.20 ± 5.29 dan 13.87 t 7.84. Grup B adalah 13.80 ± 12.68; 12.33 ± 4.39 dan 34.13 ± 12.83. Tampak jumlah netrofil lebih rendah bermakna pada jaringan pare grup A dibandingkan grup B (p < 0.009). Ada kecenderungan jumlah netrofil lebih rendah dalam jaringan otot skeletal dan hati pada grup A dibandingkan grup B, walaupun secara statistik tidak bermakna (p < 0.075).Kesimpulan. Pentoksifilin dapat mempunyai efek mengurangi infiltrasi netrofil kedalam jaringan pada kelinci yang mengalami cedera reperfusi-iskemik tungkai akut.

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Background. Ischemic-reperfusion injury is a common and important clinical issues.lt occurs in many clinical setting such as thrombo-embolic phenonrenon,atherosclerotic vascular disease, cardiovascular surgery, organ transplantation, replantation of limb etc. Reperfusion of ischemic tissue not only causing local inflammatory reaction but also affect remote organ function by systemic-inflammatory responses. Many studies have showned that polymorphonuclear leukocyte especially neutrophil has an important damaging role in reperfusion injury. They exert their effect through infiltration into ischemic tissue and also into remote organ like liver,lung,kidney etc. So far a lot of agents have been tried to attenuate reperfusion injury with variable results. One promising drug for attenuating ischemic-reperfusion injury through its anti-inflammatory effect is Pentoxifylline (PTX). In this exploratory experimental study, we observed the effect of giving PTX on neutrophil infiltration to skeletal muscle, liver and lung tissue in rabbits with induced acute limb ischemia followed by reperfusion .Methods. Twelve male New Zealand White rabbits were randomly divided into 3 groups (A,B and C). Group A were given PTX(n =5); Group B using Na CI 0.9% as a control group (n= 5); Group C was negative control (n=2). Group A and B underwent 3 hours of total ischemia of the lower limb by clamping proximal left common iliac artery, follow by 3 hours of reperfusion. The dose of intravenous PTX was 40mg1kgB W bolus followed by 1 mg/kg BWlhour maintenance dose. PTX was given 30 minutes before reperfusion. Group B was given normal saline and in Group C, no intervention done. Histopathologic section of iskernic skeletal muscle, liver, and lung tissue were taken at the end of experiment before( 3 hours of reperfusion) euthanasia was done.Results. The mean numbers ofneutrophil in ischemic skeletal musle, liver and lung tissue consecutively were as follow ; In Group C were, 0.67 t 0.75; 2.00 f 1.41; and 4.33 ± 1.49. In group Awere,3.53 ±6.0]; 7.20±5.29; and 13.87±7,84, and in groupB (control)were 13.80 ± 12.68; 12.33 ± 4.39; and 34.13 ± 12.83. There was significantly lower number of netrophil in lung tissue of group A compare to group B (p< 0.009). Although not statistically significant (p= 0.075), there were a trend to have lower neutrophil counts in ischemic skeletal muscle and liver tissue in group A rabbits compared to group B.Conclusion. Pentoxifylline has attenuating effect on neutrophil infiltration in rabbits undergoing ischemic-reperfusion injury of lower limb."