Hasil Pencarian  ::  Simpan CSV :: Kembali

"Latar belakang. Acute respiratory distress syndrome (ARDS) merupakan salah satu komplikasi fatal sepsis berat. Penggunaan cairan koloid sebagai cairan resusitasi dapat menurunkan kejadian ARDS lebih banyak karena memiliki berat molekul yang lebih tinggi dibandingkan cairan kristaloid. Peningkatan extravascular lung water (EVLW), kadar interleukin-8 (IL-8) dan vascular cell adhesion molecule-1 (VCAM-1) telah diteliti sebagai indikator penting yang berperan dalam patogenesis ARDS. Penelitian pada hewan coba diharapkan dapat memberikan penjelasan yang lebih baik mengenai patofisiologi ARDS yang kompleks dan sulit dimengerti. Tujuan. Mengungkap pengaruh cairan koloid atau kristaloid terhadap kejadian ARDS pada model hewan coba babi dengan sepsis berat, serta menganalisis pengaruh cairan kristaloid atau koloid terhadap peningkatan EVLW, IL-8, dan VCAM-1. Metode. Penelitian ini merupakan studi eksperimental acak tersamar ganda, dilakukan di Laboratorium Bedah Eksperimental, Fakultas Kedokteran Hewan, Institut Pertanian Bogor, dengan menggunakan babi (Sus scrofa) yang sehat berusia 2-3 bulan, berat badan 8-12 kg. Subjek dialokasikan secara acak menjadi dua kelompok, yaitu yang mendapatkan cairan resusitasi koloid atau kristaloid. Setelah pemberian endotoksin 50 μg/kg, tanda klinis ARDS, EVLW, IL-8, dan VCAM-1 dipantau saat sepsis, sepsis berat, 1 jam, dan 3 jam pasca-resusitasi cairan. Tiga jam pasca-resusitasi, dilakukan eutanasia pada babi, kemudian spesimen jaringan paru diambil untuk pemeriksaan histopatologi. Hasil Utama. ARDS kategori ringan lebih banyak terdapat pada kelompok koloid, sedangkan ARDS kategori sedang lebih banyak pada kelompok kristaloid. Rerata skor cedera paru pada kelompok koloid lebih rendah dibandingkan dengan kristaloid (0,4 vs. 0,7; p=0,001). Peningkatan EVLW lebih sedikit terjadi pada kelompok koloid dibandingkan dengan kristaloid pada 1 jam (1,0 vs. 3,0 mL/kgbb; p=0,030) dan 3 jam pasca-resusitasi (2,7 vs. 6,3 mL/kgbb; p=0,034). Pada kedua kelompok, kadar IL-8 meningkat secara bermakna setelah pemberian endotoksin (103,1 vs. 3854,5 pg/mL; p=0,012 pada kelompok koloid dan 125,0 vs. 4419,3 pg/mL; p=0,003 pada kelompok kristaloid). Nilai kadar IL-8 dan VCAM-1 tidak berbeda bermakna antara kedua kelompok. Simpulan. Penggunaan cairan koloid sebagai cairan resusitasi tidak menurunkan kemungkinan kejadian ARDS dibandingkan kristaloid. Cairan koloid berhubungan dengan peningkatan EVLW dan skor cedera paru yang lebih rendah dibandingkan dengan cairan kristaloid, tetapi tidak pada kadar IL-8 dan VCAM-1.

---

Background. Acute respiratory distress syndrome (ARDS) is a fatal complication of severe sepsis. Due to its higher molecular weight, the use of colloids in fluid resuscitation may be associated with fewer cases of ARDS compared to crystalloids. Extravascular lung water (EVLW) elevation and levels of interleukin-8 (IL-8) and vascular cell adhesion molecule-1 (VCAM-1) have been studied as indicators playing a role in the pathogenesis of ARDS. The use of animal models may provide a better understanding of the complex and poorly understood pathophysiology of ARDS.

Objectives. To determine the effects of colloid or crystalloid fluid resuscitation on the incidence of ARDS, elevation of EVLW, and levels of IL-8 and VCAM-1, in swine models with severe sepsis.

Methods. This was a randomized trial conducted at the Laboratory of Experimental Surgery, School of Veterinary Medicine, Institut Pertanian Bogor, using healthy swine (Sus scrofa) models aged 2 to 3 months with a body weight of 8 to 12 kg. Subjects were randomly allocated to receive either colloid or crystalloid fluid resuscitation. After administration of 50 μg/kgbw of endotoxin, clinical signs of ARDS, EVLW, IL-8, and VCAM-1 were monitored during sepsis, severe sepsis, and one- and three hours after fluid resuscitation. Three hours after resuscitation, euthanasia was performed on the animal and the lung tissue specimen was taken for histopathological examination.

Results. Mild ARDS was more prevalent in the colloid group, while moderate ARDS was more frequent in the crystalloid group. Mean lung injury score was lower in colloid compared to crystalloid group (0.4 vs. 0.7; p=0.001). The increase in EVLW was lower in the colloid compared to the crystalloid group both at one hour (1.0 vs. 3.0 mL; p=0.030) and three hours post-resuscitation (2.7 vs. 6.3 mL/kg; p=0.034). In both groups, IL-8 levels were significantly higher after endotoxin administration (103.1 vs. 3854.5 pg/mL; p=0.012 in the colloid group and 125.0 vs. 4419.3 pg/mL; p=0.003 in the crystalloid group). There was no significant difference in IL-8 and VCAM-1 levels between the two groups.

Conclusion. The use of colloids in fluid resuscitation does not decrease the probability of ARDS events compared to crystalloids. Compared to crystalloids, colloids are associated with a lower increase in EVLWI and a lower mean lung injury score, but not with IL-8 or VCAM-1 levels."

"Insidens insufisiensi adrenal pada pasien renjatan sepsis dilaporkan sekitar 40-65. Sitokin IL-1 dan IL-6 dapat menstimulasi sekresi kortisol sedangkan TNF-? serta MIF berperan dalam menghambat pembentukan kortisol. Penelitian ini bertujuan untuk mengetahui peran IL-1, IL-6, TNF-? dan MIF dalam terjadinya insufisiensi adrenal relatif pada renjatan sepsis.Penelitian eksperimental dilakukan di laboratorium FKH IPB berlangsung selama 6 bulan April-September 2015 . Model anak babi yang dipakai berumur 6-8 minggu dengan berat badan 5-10 kg. Pemilihan sampel dengan consecutive sampling dengan total n = 20. Anak babi diberikan infus endoktoksin dengan dosis 50 ug/kg BB. Sampel darah untuk analisis IL-1, IL-6, TNF-?, MIF, ACTH, kortisol, 17 OHP, DHEA, androstenedion diambil sebelum pemberian endotoksin dan tiap 15 menit hingga terjadi renjatan sepsis, kemudian dilakukan uji synacthen. Pemeriksaan imunohistokimia dilakukan pada kelenjar adrenal, hipofisis, dan hipotalamus.Dari 19 anak babi yang dianalisis mengalami renjatan sepsis dalam waktu 60 menit. Karakteristik sampel tidak berbeda bermakna antara kedua kelompok. Kadar IL-6 pada kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada menit ke-45 0,65 0,5-4,32 pg/dL vs. 0,54 0,51-0,61 pg/dL , p = 0,008 . Kadar IL-1 antara kelompok IAR dibandingkan kelompok tanpa IAR tidak berbeda bermakna. Kadar TNF-? pada kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada menit ke-15 1862,5 327,9-4511,14 pg/dL vs. 155,38 24,67-394,10 pg/dL , p = 0,002 dan menit ke-30 4295,76 246,9-5913,37 pg/dL vs. 422,90 101,05-4129,42 pg/dL , p = 0,007 . Kadar MIF kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada saat renjatan sepsis 25,28 18,45-30,64 ng/dL vs. 11,30 7,1-15,14 ng/dL p = 0,003 . Pemeriksaan imunohistokimia hanya pada hipotalamus yang menunjukkan pewarnaan terhadap IL-1, IL-6, TNF-? dan MIF pada kelompok dengan IAR. Pada renjatan sepsis dan insufisiensi adrenal relatif kadar TNF-? meningkat pada menit-menit awal, kemudian kadar IL-6 meningkat kemudian serta terakhir kadar MIF meningkat pada saat renjatan sepsis. Kadar IL-1 tidak terdapat perbedaan antara kedua kelompok. Kata kunci: IL-1, IL-6, insufisiensi adrenal relatif, MIF, renjatan sepsis, TNF-?

---

Incidence of adrenal insufficiency in septic shock ranged between 40 ndash 65 . The mechanism of relative adrenal insufficiency in septic shock is caused by inflammatory mediators. This study aimed to identify the role of IL 6, IL 1 in stimulating ACTH and cortisol release, and the role of TNF and MIF in inhibiting the level of ACTH and cortisol in septic shock with relative adrenal insufficiency RAI in order to develop guidelines for relative adrenal insufficiency marker.Experimental study was conducted in Veterinary Faculty, Bogor Agricultural Institute for 6 months Apri ndash September 2015 . Piglet models Sus scrofa aged 6 ndash 8 weeks weighing 5 ndash 10 kg. Consecutive sampling was used with total 20 piglets. Piglet models were given 50 ug kg endotoxin infusion Escherichia coli O111 B4 Sigma chemical, St. Louis, MO, USA . Blood sample for analysis of IL 1, IL 6, TNF , MIF, ACTH, cortisol, 17 OHP, DHEA, androstenedione was collected before endotoxin administration and every 15 minutes until septic shock occurred. Piglet models were monitored using PiCCO monitor. Stimulation test was then performed using synthetic corticotropin Synacthen and blood sample was collected again along with immunohistochemistry examination of the adrenal, pituitary and hypothalamus glands.From 19 study subjects analized, all subject had septic shock in 60 minutes. Study subject characteristics in each group were similar. The level of IL 6 at 45 minutes had a significant different compared to the group without RAI 0.65 0.5 ndash 4.32 pg dL vs. 0.54 0.51 ndash 0.61 pg dL , p 0.008 . The level of IL 1 during septic shock were not significantly different between both groups. The level of TNF in RAI group had significant different compared to the group without RAI at 15 minutes 1862.5 327.9 ndash 4511.14 pg dL vs. 155.38 24.67 ndash 394.10 pg dL , p 0.002 and at 30 minutes 4295.76 246.9 ndash 5913.37 pg dL vs. 422.90 101.05 ndash 4129.42 pg dL , p 0.007 The level of MIF in group with RAI during septic shock had a significant different compared to the group without RAI t 25.28 18.45 ndash 30.64 ng dL vs. 11.30 7.1 ndash 15.14 ng dL , p 0.003 . Immunohisto chemistry staining of IL 1, IL 6, TNF , and MIF was observed only in the hypothalamus glands of the RAI group. In septic shock and relative adrenal insufficiency, TNF increased in earlier minutes, then IL 6 increased and later MIF increased in septic shock condition. IL 1 level had no difference increment for both group.Keywords IL 1, IL 6, MIF, relative adrenal insufficiency, septic shock, TNF"

"ABSTRAKInflamasi sistemik pada renjatan sepsis dapat menyebabkan insufisiensi adrenal. Kadar asam lemak bebas ALB yang tinggi diketahui menyebabkan inflamasi steril dan menghambat adrenocorticothropic hormone dan sekresi kortisol. Pemberian hidrokortison pada renjatan sepsis diharapkan memperbaiki hemodinamik, menurunkan ketergantungan terhadap obat vasoaktif dan memperbaiki disfungsi organ.Penelitian bersifat studi eksperimental yang bertujuan menilai pengaruh ALB dan pemberian hidrokortison terhadap hemodinamik, kadar laktat, cedera paru dan kadar kortisol darah pada renjatan sepsis model anak babi. Penelitian dilaksanakan di Divisi Bedah dan Radiologi Departemen Klinik Reproduksi dan Patologi Fakultas Kedokteran Hewan Institut Pertanian Bogor FKH IPB pada April -September 2015 dan telah disetujui oleh Komisi Etik Hewan FKH IPB.Delapan model anak babi Sus scrofa berusia 6-8 minggu dengan berat 5-10 kg dibagi dalam 2 kelompok, yaitu kelompok lipid dan kelompok kontrol. Kelompok lipid diberi lipid 20 sebanyak 3 gram/kgbb intravena dan kelompok kontrol tanpa pemberian lipid sebelum induksi sepsis. Pengukuran parameter hemodinamik dengan Pulse Contour Cardiac Output PiCCO . Pengukuran kadar laktat dengan i-Stat. Cedera paru ditentukan dengan pengukuran extravascular lung water index EVLWI dan rontgen toraks. Tes synacthen dilakukan untuk mengetahui adanya insufisiensi adrenal relatif IAR .Pengaruh ALB terhadap hemodinamik dinilai dengan rerata cardiac index 60 menit setelah pemberian hidrokortison yang berbeda bermakna [2,14 0,06 l/menit/m2 vs. 2,75 0,04 l/menit/m2 p 0,002 ]. Jumlah cairan dan obat vasoaktif yang dibutuhkan kelompok lipid untuk mempertahankan mean arterial blood pressure > 65 mmHg lebih banyak dibandingkan kelompok kontrol. Kadar laktat meningkat sebelum induksi sepsis pada kelompok lipid [2,28 0,52 vs. 1,28 0,45 mmol/L p 0,001 ]. Bersihan laktat pada kelompok lipid lebih buruk dibandingkan kelompok kontrol. Extravascular lung water index kelompok lipid lebih tinggi bermakna dibanding kelompok kontrol setelah 60 menit resusitasi [21 4,04 mL/kg vs. 12,38 2,32 mL/kg p 0,004 ]. Gambaran radiologi efusi pleura dan edema pulmonal terjadi pada seluruh model anak babi kelompok lipid. Insufisiensi adrenal relatif terjadi pada 7 model anak babi di kelompok lipid dan 4 di kelompok kontrol.Kesimpulan penelitian ini adalah kadar ALB yang tinggi memperberat inflamasi dan merupakan faktor risiko terjadinya IAR. Kata kunci: Asam lemak bebas, cedera paru, hemodinamik, hidrokortison insufisiensi adrenal relatif, laktat, renjatan sepsis, sepsis.

---

ABSTRACTCortisol deficiency is associated with increased morbidity and mortality during critical illness. Dysregulation of immune system in septic shock triggers adrenal insufficiency. Free fatty acid FFA is known to induced sterile inflammation and inhibit adrenocorticothropic hormone and cortisol secretion. Hydrocortisone administration is expected to improve hemodynamic, decrease dependency of vasoactive drugs and improve organ dysfunction in septic shock.The aim of this study is to find out the effect of FFA and hydrocortisone administration on hemodynamic parameters, lactate, lung injury and blood cortisol levels in septic shock piglet models, conducted in April September 2015 in the Division of Surgery and Radiology School of Veterinary Medicine, Institut Pertanian Bogor IPB and has been approved by the Animal Ethics Committee of School of Veterinary Medicine IPB. Sixteen piglet models Sus scrofa entered the study. The piglets were 6 8 weeks old, weighing 5 10 kg divided into two groups, lipids and control groups. Administration of 3 g kg BW of lipid 20 were performed intravenously before sepsis induction for lipid group. Hemodynamic measurement by Pulse Contour Cardiac Output PiCCO by Picco. Lactate measurement by i Stat. Lung injury was determined by Extravascular lung water index EVLWI and chest X ray. Synacthen test to determine relative adrenal insufficiency RAI .FFA influences was shown on cardiac index 60 min after adminstration of hydrocortisone in lipid group 2.14 0.06 L min m2 and control group 2.75 0.04 L min m2 p 0.002 . Lipid group require fluids and vasoactive drugs more than the control grup to maintain mean arterial blood pressure 65 mmHg. Lactate levels before induction of sepsis lipid group 2.28 0,52 mmol L and control group 1.28 0.45 mmol L p 0.001 . Lactate clearance in lipid group was worse than the control group. Extravascular lung water index at 60 minutes after resuscitation in lipid group 21 4.04 mL kg and control group 12.38 2.32 mL kg p 0.004 . Pleural effusion and pulmonary edema were found in all piglet models in lipid group. Relative adrenal insufficiency occured to 7 piglet model in lipid gorup and 4 in control group.Conclusion High level FFA aggravate inflammation in septic shock and is a risk factor for RAI. Hydrocortisone administration improve circulation and lactate levels. Keywords FFA, hemodynamic, hydrocortisone, lactate, lung injury, relative adrenal insufficiency, sepsis, septic shock"

"Panduan resusitasi anak umumnya menganjurkan pemberian cairan dalam jumlah besar. Beberapa penelitian memperlihatkan bahwa penggunaan cairan yang agresif meningkatkan mortalitas. Penelitian pada hewan menunjukkan tekanan vena sentral yang tinggi memicu pelepasan atrial natriuretic peptide ANP , sementara penelitian invitro memperlihatkan ANP meluruhkan glycocalyx endotel vaskular dan meningkatkan permeabilitas endotel. ANP juga memicu vasodilatasi. Hemodilusi berpotensi menurunkan pasokan oksigen tubuh DO2 . Penelitian bertujuan untuk melihat pengaruh resusitasi cairan terhadap kadar ANP serum, peluruhan glycocalyx endotel vaskular, extravascular lung water index ELWI , mean arterial pressure MAP , kadar hemoglobin dan pasokan oksigen. Hewan model renjatan adalah 11 ekor Sus scrofa jantan, usia 6-10 minggu. Renjatan dilakukan dengan metode fixed pressure hemorrhage. Resusitasi pertama dilakukan dengan jumlah cairan sesuai darah yang dikeluarkan resusitasi normovolemik , dilanjutkan dengan 40 mL/kg resusitasi hipervolemik . Pengukuran hemodinamik dilakukan dengan PICCO. Serum ANP dan Syndecan-1, petanda peluruhan glycocalyx, dilakukan dengan teknik ELISA. Hasil penelitian menunjukkan terjadinya peningkatan ANP pasca resusitasi normovolemik p = 0,043 , yang kemudian menurun kembali dalam 30 menit. Peluruhan glycocalyx tidak terjadi. Perbedaan ELWI pada 60 menit pasca resusitasi secara statistik bermakna, dengan perbedaan 0,93 mL/kg 95 IK:0,19 -3,62 . Terdapat korelasi kuat antara SVRI dan CI pasca resusitasi hipervolemik r = -0,587 . Tidak ada perbedaan MAP pasca resusitasi normovolemik dan hipervolemik. Kadar hemoglobin pasca resusitasi hipervolemik lebih rendah daripada pasca resusitasi normovolemik p = 0,009 . Pasokan oksigen tubuh pasca resusitasi hipervolemik lebih tinggi daripada pasca resusitasi normovolemik p = 0,012 . Simpulan: Resusitasi cairan pada renjatan akibat perdarahan tidak mengakibatkan peluruhan glycocalyx endotel vaskular. Peningkatan ELWI amat terbatas. SVRI berkorelasi terbalik dengan CI. Tidak ada perbedaan MAP antara resusitasi normovolemik dan hipervolemik. Resusitasi hipervolemik menyebabkan hemodilusi yang diimbangi dengan peningkatan curah jantung.

---

Many pediatric guidelines recommend liberal fluid resuscitation, but recent studies showed that aggressive fluid resuscitation might increase mortality. Animal studies showed that high central venous pressure induced ANP secretion. Invitro studies showed convincing evidence that ANP induced glycocalyx shedding. ANP also induced vasodilatation through cGMP signal transduction pathways. Hemodilution due to a large amount of resuscitation fluid potentially decreasing oxygen delivery.The objectives of this study were investigating the effect of fluid resuscitation, in the animal model, with special concern on serum ANP, glycocalyx shedding indicate by serum Syndecan-1 , changes in extravascular lung water, systemic vascular resirtance and mean arterial pressure, hemoglobin level and oxygen delivery DO2 . The animal models were 11 male domestic pigs, 6 -10 weeks old. The shock was induced with fixed pressure hemorrhage method. Fluid resuscitation was done in 2 phases. On the first attempt, we replaced total numbers of blood that withdrawn normovolemic resuscitation . On the second attempt, we gave 40 mL/kg resuscitation fluids hypervolemic resuscitation . The hemodynamic measurements were done with PICCO. Serum ANP and Syndecan-1 were measure with ELISA method.We found that serum ANP increased after normovolemic resuscitation p = 0.043 and immediately back to base level in 30 minutes. Glycocalyx shedding did not occur. Extravascular lung water index minimally increased. There was a strong correlation between SVRI and CI at hypervolemic resuscitation r = -0.587 . There was no difference in mean arterial pressure between normovolemic and hypervolemic resuscitation. Hemoglobin level after hypervolemic resuscitation was lower than after normovolemic resuscitation p = 0.009 . Oxygen delivery was higher after hypervolemic resuscitation p = 0.012 .Conclusions: Hypervolemic resuscitation in this hemorrhagic shock model did not induce glycocalyx shedding, extravascular lung water index minimally increased. Systemic vascular resistance index negatively correlated to cardiac index. Fluid resuscitation may induce hemodilution, but oxygen delivery can be compensated by increasing cardiac output. "

"Infark miokard menyebabkan kematian kardiomiosit dan remodeling jantung pada situasi patologis. Pascainfark jantung tidak mampu mengatasi kehilangan kardiomiosit meskipun telah dilakukan rekanalisasi atau revaskularisasi. Oleh karena itu, diperlukan metode untuk mengembalikan fungsi jantung. Sel punca dapat memperbaharui diri dan berdiferensiasi menjadi berbagai tipe sel namun kesintasannya pada pasien masih rendah. Untuk meningkatkan retensi dan regenerasi sel punca di miokardium dapat digunakan perancah/scaffold dan sistem ko-kultur, namun belum ada penelitian tentang hal tersebut. Penelitian ini bertujuan mengembangkan terapi infark menggunakan injeksi hidrogel transepikardial dan implantasi di epikardial perancah patch membran amnion yang dideselularisasi menggunakan amniotic epithelial cells (AEC) dengan ko-kultur kardiomiosit. Penelitian ini menggunakan post-test only control group design yang dilakukan di Institut Pertanian Bogor dan Fakultas Kedokteran Universitas Indonesia dari Juli 2021–Oktober 2022. Subjek penelitian adalah 15 babi Sus scrofa domesticus usia 2-3 bulan dibagi tiga kelompok: pAEC, pAEC + kardiomiosit, kontrol positif, dan 1 babi sebagai kontrol negatif. Torakotomi dilakukan untuk membuat model infark dengan ligasi arteri proximal branch to left ventricle (PLV) dilanjutkan implantasi pAEC dengan atau tanpa ko-kultur kardiomiosit pada kelompok terapi, kemudian diobservasi selama 6–8 minggu. Luas infark diukur dengan late gadolinium enhancement MRI; remodeling ventrikel kiri dengan ekokardiografi untuk menilai kontraktilitas, fibrosis dengan IHK, kardiomiogenesis dan regulasi apoptosis dengan RT-PCR, angiogenesis dinilai dengan IHK, dan fraksi ejeksi dinilai dengan ekokardiografi. Luas infark menurun pada kedua kelompok terapi (2,5 [2,00–3,00]% dan 3,60 ± 1,34% vs 9,50 ± 1,91%). Pewarnaan HE dan Masson trichrome menunjukkan berkurangnya proses fibrosis pada kedua kelompok, dikonfirmasi dengan hiperekspresi kolagen1 yang padat dan kaku pada kontrol positif dibandingkan kedua kelompok terapi yang memiliki ekspresi kolagen3 lebih dominan. Ekspresi α-smooth muscle actin pada kedua kelompok tampak tersebar menunjukkan penurunan fibrosis dan kontrol positif menunjukkan peningkatan fibrosis. Peningkatan kardiomiogenesis pada kedua kelompok dikonfirmasi dengan peningkatan ekspresi gen cardiac troponin T, gen myosin heavy chain, gen Nkx.2.5, gen c-Kit, dan penanda otot fungsional α-actinin. Penurunan apoptosis dikonfirmasi dengan penurunan ekspresi gen modulator apoptosis p21 dan ekspresi gen p53 yang berarti diferensiasi sel punca tidak bersifat tumorigenik. Regulasi apoptosis melalui ekspresi kaspase-9 tidak berbeda bermakna. Peningkatan angiogenesis dikonfirmasi dengan peningkatan ekspresi von Willebrand Factor dan ekspresi α-smooth muscle actin yang tersebar. Ekokardiografi menunjukkan perbaikan regional wall motion abnormality lebih banyak pada kelompok terapi daripada kontrol positif dan fraksi ejeksi tidak berbeda bermakna antar kelompok. Disimpulkan kombinasi injeksi hidrogel transepikardial dan implantasi di epikardial perancah patch membran amnion yang dideselularisasi dengan ko-kultur AEC dan kardiomiosit dapat mengurangi luas infark dan remodelling ventrikel kiri, serta meningkatkan angiogenesis pada babi model infark.

---

Myocardial infarction induces cardiomyocyte death and remodelling a pathological condition. The post-infarct heart is unable to deal with cardiomyocyte loss despite recanalization or revascularization. Therefore, a procedure is required to restore cardiac function. Stem cells can self-renew and specialize into multiple cell types however the survival of stem cells in patients is still poor. To promote the retention and regeneration of stem cells in the myocardium, scaffolds and co-culture systems may be applicated, although there are no study findings on this issue. This study aimed to develop myocardial infarction therapy using transepicardial hydrogel injection and epicardial decellularized amniotic membrane scaffold patch implantation using amniotic epithelial cells (AEC) with cardiomyocyte co-culture. This study used a post-test-only control group design performed at the IPB University and the Faculty of Medicine, Universitas Indonesia, from July 2021 to October 2022. The study subjects were 15 Sus scrofa domesticus pigs aged 2-3 months placed into three groups: pAEC, pAEC + cardiomyocytes, positive control, and 1 pig as a negative control. Thoracotomy was conducted to create an infarct model with the proximal branch to left ventricle (PLV) artery occlusion followed by pAEC implantation with or without cardiomyocyte co-culture in the therapy group, then evaluated for 6–8 weeks. Infarct size was determined by late gadolinium enhancement MRI, left ventricular remodeling by echocardiography to evaluate contractility, fibrosis by IHC, cardiomyogenesis and regulation of apoptosis by RT-PCR, angiogenesis was assessed by IHC, and ejection fraction by echocardiography. Infarct size reduced in both therapy groups (2,5 [2,00–3,00]% and 3,60 ± 1,34% vs 9,50 ± 1,91%). HE and Masson trichrome staining demonstrated decreased fibrosis in both groups, confirmed by hyperexpression of dense and stiff collagen 1 in the positive control compared to the two therapy groups with more dominant collagen 3 expressions. The α-smooth muscle actin expression in both groups seemed to be scattered suggesting reduced fibrosis while the positive control showed increased fibrosis. Increased cardiomyogenesis in both groups was confirmed by increased expression of the cardiac troponin T gene, the myosin heavy chain gene, the Nkx.2.5 gene, the c-Kit gene, and the functional muscle marker α-actinin. The reduction in apoptosis has been confirmed by lower expression of the p21 apoptosis modulator gene and p53 gene expression, which suggests that stem cell differentiation is not tumorigenic. The control of apoptosis by caspase-9 expression was not significantly different. Increased angiogenesis was verified by increased von Willebrand Factor expression and scattered expression of α-smooth muscle actin. Echocardiography showed greater improvement in regional wall motion abnormalities in the therapy groups than in the positive control, and the ejection fraction was not significantly different between groups. It was concluded that the combination of transepicardial hydrogel injection and epicardial decellularized amniotic membrane scaffold patch implantation using AEC with cardiomyocyte co-culture could reduce infarct size and left ventricular remodeling, as well as increase angiogenesis in infarct model pigs."