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• W3208516907 abstract "Introduction: There is no standardized and widely used model of severe acute pancreatitis (SAP) with organ failure. This may limit drug development for severe acute pancreatitis. Dysregulated and hyperimmune responses are the root cause of organ failure in SAP. We established a rat model of SAP with organ failure and evaluated clinically relevant parameters of organ dysfunction such as blood pressure and arterial blood gas analysis. We also evaluated the effects of therapeutic administration of methylprednisolone (MP) and TNF-α antibody infimab (Infliximab biosimilar) on the severity of experimental SAP induced in rats by the ligation of the main pancreatic duct. Methods: After obtaining ethical clearance, SAP was induced in adult male Wistar rats weighing between 250-350 g by ligation of the main pancreatic duct proximal to its entrance into the bile duct. One-hour after surgery, the therapeutic medication was administered intraperitoneally. Experiments were done in duplicate in batches of 3 rats each in sham surgery, SAP, SAP + MP, and SAP + infimab groups. At 0 (pre intervention) and 48 hours (post intervention) from induction, invasive BP, heart rate, albumin in broncho-alveolar lavage, serum amylase, lactate, paO2, SpO2, pH, renal and liver function were measured. The rats were sacrificed at 48 hours and the harvested pancreas, kidney and lung tissues were assessed histopathologically. Results: There was a significant increase in serum amylase level (p = 0.019) and histopathological scores (p = 0.003) in the AP group as compared to sham surgery with no significant effect of either MP or Infimab (amylase: p = 0.211, histopathological score: p = 0.103). Both MP and Infimab significantly prevented a fall in BP and decrease in SpO2 following induction of SAP compared to the vehicle control (Table 1). Conclusions: Therapeutic administration of MP or Infimab ameliorates the systemic inflammation and organ dysfunction associated with SAP in rats.FP16.07_Table 1Comparison of pre intervention and post intervention parameters between vehicle control, therapeutic methylprednisolone and therapeutic infimabSAP (Vehicle control)SAP + IP MethylprednisoloneSAP + IP Infimabp value for between group comparison of change* following intervention (vehicle control vs MP vs Infimab )Change* following Interventionp value of change*Change following Interventionp value of change*Change* following Interventionp value of change*Amylase (IU/L)2681 (1072 to 3753)0.0043260 (1490 to 9960)0.0621457.5 (370 to 2350)0.0310.211Mean BP (mmHg)-15.4 (-17 to -13.4)0.004-3.6 (-6 to 6)0.688-19.3 (-28.6 to -3.9)0.0940.023Heart Rate (beats/min)-47 (-57.1 to -36.5)0.004-6.4 (-31.3 to -2.3)0.313-15.1 (-37.3 to 1.8)0.4380.133Blood Lactate (mmol/L)2.3 (0.7 - 2.7)0.0091.8 (1.2 - 2.3)0.0312.05 (0.2 - 2.3)0.0630.845SpO2 (%)-3.5 (-9.5 to -1.9)0.008-0.5 (-5.9 to 2.9)0.688-0.4 (-0.2 to 0)0.5840.176pO2 (mmHg)-5 (-31.9 to -0.9)0.074-3.7 (-65.6 to 9.5)0.563-6.7 (-16.1 to 1.9)0.2190.786 Open table in a new tab *change refers to the difference between pre - intervention and post - intervention values" @default.
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• W3208516907 date "2021-01-01" @default.
• W3208516907 modified "2023-09-27" @default.
• W3208516907 title "Therapeutic Methylprednisolone and Infimab Decrease the Severity of Organ Dysfunction in Pancreatic Duct Ligation Model of Severe Acute Pancreatitis in Wistar Rats" @default.
• W3208516907 doi "https://doi.org/10.1016/j.hpb.2021.08.136" @default.
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