IDDF2024-ABS-0221 Anticoagulant and anti-inflammatory treatments alleviate inflammation and multi-organ damage in acute pancreatitis by improving pancreatic blood flow perfusion

<h3>Background</h3> This study investigated the correlation between pancreatic blood flow perfusion, inflammation, and multi-organ damage in acute pancreatitis (AP) aiming to explore the mechanisms underlying the efficacy of anticoagulant and anti-inflammatory treatments in reducing inflammation and multi-organ damage in AP. <h3>Methods</h3> 40 Sprague-Dawley rats were randomly divided into five groups: control, AP, heparin, parecoxib, and combined medication. Pancreatic blood flow perfusion was assessed using a laser speckle blood flow imaging system. TNF-α, IL-6, platelet-activating factor (PAF) and thromboxane A2 (TXA2) levels was measured by enzyme-linked immunosorbent assay. Microthrombus density was visualized through fibrin staining. Lung edema was assessed by the lung wet weight/dry weight ratio. Multi-factor correlation analysis was used for multiple linear regression analysis. <h3>Results</h3> Compared to control group, rats in AP group demonstrated a significant reduction in the pancreatic blood flow perfusion and 24-hour urine output with increased serum TNF-α, IL-6, PAF levels, pancreatic histopathological score, microthrombus density, and severity of lung edema. Compared to AP group, heparin, parecoxib, and combined medication groups exhibited increased pancreatic blood flow perfusion and 24-hour urine output, along with decreased serum TNF-α level, microthrombus density, and severity of lung edema. After anticoagulant and/or anti-inflammatory treatment, pancreatic histopathological scores concerning edema, leukocyte infiltration, hemorrhage, and acinar cell necrosis markedly decreased. Serum IL-6 level in AP rats was dramatically reduced by heparin and combined medication, while parecoxib had no effect. However, heparin, parecoxib and combined medication had no effect on serum PAF level when compared to the AP group. There was no significant difference in serum TXA2 level between the five groups. Serum TNF-α level, pancreatic microthrombus density and histopathological score were negatively correlated with pancreatic blood flow perfusion, while serum PAF level, and severity of lung edema were positively correlated with pancreatic blood flow perfusion. <h3>Conclusions</h3> Anticoagulant and anti-inflammatory therapies, alone or combined, significantly improved organ blood flow perfusion, reduced inflammation, and mitigated organ damage during AP. Notably, pancreatic blood flow perfusion correlates significantly with circulating TNF-α level and damage to the pancreas, kidneys, and lungs.