Efficacy of Continuous Regional Arterial Infusion With Low-Molecular-Weight Heparin for Severe Acute Pancreatitis in a Porcine Model

Abstract

Administration of heparin or its derivatives has been proved to be beneficial in the treatment of severe acute pancreatitis (SAP). However, drugs administered by conventional intravenous way are difficult to reach the pancreatic tissue and may cause bleeding complications due to coagulation and microcirculatory disturbance following initiation of SAP. In this study, we aimed to assess the effects of low-molecular-weight heparin (LMWH) administered with continuous regional arterial infusion (CRAI) technique in a porcine model of SAP. Following baseline measurements, 18 animals were divided into three groups: CRAI group (LMWH infused through placed arterial catheter), venous group (LMWH infused through central venous catheter), and SAP control group. We used retrograde intraductal infusion of sodium taurocholate to induce SAP. Global hemodynamic profiles, urine output, systemic oxygenation, and inflammatory and serum biochemical parameters of the animals were studied. At the end of the experiment, histological examination of pancreas, intestine, and lung was performed. Continuous regional arterial infusion with LMWH remarkably stabilized hemodynamic profiles, improved systemic oxygenation and peripheral perfusion, alleviated histological injury of pancreas (especially for the necrosis scale), and downregulated inflammatory response when compared with the other two groups. Moreover, serum D-dimer level also decreased most significantly in the CRAI group (474 ± 144 vs. 664 ± 155 µg/L in the venous group and 945 ± 351 µg/L in the controls at the end), partly indicating ameliorated coagulation disorders in the study group. No bleeding complication was observed in the CRAI group, whereas two animals in the venous group presented gastrointestinal hemorrhage. Continuous regional arterial infusion with LMWH exhibits strong therapeutic effects in the course of SAP with great safety. Human studies using this novel therapy are required to assess these potential benefits in the clinical setting.