EFEK KOMBINASI RESUSITASI CAIRAN DAN NOREPINEFRIN TERHADAP MORFOPATOLOGI USUS BABI PADA MODEL SYOK ENDOTOKSIK

Abstract

Syok endotoksik dapat menyebabkan gangguan hemodinamik dan perubahan mukosa usus yang tidak selalu membaik sejalan dengan perbaikan tekanan darah sistemik setelah resusitasi cairan dan norepinefrin. Penelitian ini bertujuan mendeskripsikan perubahan makroskopis dan histopatologis duodenum, jejunum, ileum, dan kolon serta membandingkan skor komposit kerusakan histopatologis pada tingkat hewan di antara kelompok yangmenerima paparan endotoksin dan/atau regimen hemodinamik yang berbeda. Sebanyak 17 ekor anak babi jantan (Sus scrofa domesticus) yang berumur 8- 12 minggu dengan berat badan 35-40 kg dibagi menjadi lima kelompok, yaitu R (n = 3), NE (n = 2), E+R (n = 4), E+NE (n = 4), dan E+R+NE (n = 4). Syok endotoksik diinduksi menggunakan lipopolisakarida Escherichia coli hingga tekanan arteri rata-rata (MAP) < 65 mmHg. Duodenum, jejunum, ileum, dan kolon dievaluasi secara makroskopis dan histopatologis menggunakan pewarnaan hematoksilineosin serta sistem skoring semikuantitatif. Babi merupakan unit eksperimen, sedangkan keempat segmen usus merupakan pengukuran berulang pada hewan yang sama. Skor keempat segmen dirangkum menjadi satu skor komposit per hewan. Perbandingan skor komposit antarkelompok dianalisis menggunakan uji Kruskal-Wallis, dilanjutkan dengan uji Dunn dan koreksi perbandingan berganda, sedangkan perbedaan skor antarsegmen dianalisis menggunakan uji Friedman. Secara makroskopis, kelompok Rdan NE tidak menunjukkan edema, petekie, atau hemoragi nyata, sedangkan kelompok endotoksin menunjukkan hiperemia, edema, penebalan dinding usus, petekie, dan hemoragi fokal dengan keparahan bervariasi. Pemeriksaan histopatologis menunjukkan atrofi vili, deskuamasi dan nekrosis epitel, perubahan jumlah sel goblet, kongesti vaskular,serta hemoragi pada keempat segmen usus. Analisis tingkat hewan menunjukkan perbedaan skor komposit di antara kelima kelompok (?² = 10,26; db = 4; p = 0,0362), tetapi uji lanjut tidak menunjukkan perbedaan bermakna setelah koreksi perbandingan berganda. Secara deskriptif, skor komposit kelompok E+NE lebih rendah daripada E+R, sedangkan E+R+NE memiliki skor tertinggi, tetapi perbedaan tersebut belum terkonfirmasi secara statistik. Skor kerusakan histopatologis juga tidak berbeda secara bermakna antarsegmen usus (?² = 6,26; db = 3; p = 0,0997). Penelitian ini menunjukkan adanya variasi perubahan morfopatologismukosa usus antarkelompok, tetapi belum dapat menentukan regimen yang paling baik dalam mempertahankan integritas mukosa usus. Karena tidak terdapat kelompok endotoksin tanpa terapi, pengaruh kausal resusitasi cairan, norepinefrin, atau kombinasi keduanya terhadap kerusakan mukosa usus belum dapat dipastikan. Temuan ini menjadi dasar bagi penelitian lanjutan dengan jumlah hewan yang lebih besar, kelompok pembanding yang memadai, serta pengukuran langsung mikrosirkulasi dan fungsi sawar usus.

Endotoxic shock can cause hemodynamic disturbances and intestinal mucosal changes that do not necessarily improve with systemic blood pressure following fluid resuscitation and norepinephrine administration. This study aimed to describe macroscopic and histopathological changes in the duodenum, jejunum, ileum, and colon and compare animal-level composite histopathological injury scores among groups exposed to endotoxin or different hemodynamic regimens. Seventeen male piglets were allocated to five groups: fluid resuscitation without endotoxin (R; n = 3), norepinephrine without endotoxin (NE; n = 2), Escherichia coli endotoxin with fluid resuscitation (E+R; n = 4), endotoxin with norepinephrine (E+NE; n = 4), and endotoxin with combined fluid resuscitation and norepinephrine (E+R+NE; n = 4). Endotoxic shock was induced using E. coli lipopolysaccharide until mean arterial pressure (MAP) < 65 mmHg. The duodenum, jejunum, ileum, and colon were evaluated macroscopically and histopathologically using hematoxylin-eosin staining and a semiquantitative scoring system. Each pig was considered an experimental unit, with the four intestinal segments as repeated measurements within the same animal. Scores from the four intestinal segments were summarized into a single composite score for each animal. Composite scores were compared among groups using the Kruskal-Wallis test, followed by Dunn’s test with multiple-comparison correction. Differences in histopathological scores among the four intestinal segments were analyzed using the Friedman test. Macroscopically, the Rand NE groupsshowed no apparent edema, petechiae, or hemorrhage, whereas endotoxin-exposed groups exhibited hyperemia, edema, intestinal wall thickening, petechiae, and focal hemorrhage of varying severity. Histopathological examination revealed villous atrophy, epithelial desquamation and necrosis, altered goblet cell numbers, vascular congestion, and hemorrhage in all four intestinal segments. Animal-level analysis showed an overall difference in composite scores among the five groups (?² = 10.26; df = 4; p = 0.0362), but no pairwise comparison remained significant after multiple-comparison adjustment. Descriptively, E+NE had a lower composite score than E+R, whereas E+R+NE had the highest score, but these differences were not statistically confirmed. Histopathological injury scores did not differ significantly among the duodenum, jejunum, ileum, and colon (?² = 6.26; df = 3; p = 0.0997). This study demonstrated variation in intestinal mucosal morphopathology among the groups but did not establish which regimen was most effective in preserving mucosal integrity. Because an untreated endotoxin group was not included, the effects of fluid resuscitation, norepinephrine, or their combination on intestinal mucosal injury could not be established. These findings provide a basis for further studies with larger sample sizes, appropriate comparator groups, and direct assessments of intestinal microcirculation and barrier function.