Renal Microcirculation in Experimental Acute Pancreatitis of Dogs

Abstract

In order to understand the mechanism of acute renal failure frequently observed in severe acute pancreatitis, renal microcirculation and renal hemodynamics were investigated during experimental acute pancreatitis in dogs induced by autologous bile and trypsin mixture into the pancreatic duct. Renal tissue blood flow (hydrogen gas clearance method), renal arterial blood flow, and cardiac output (transonic blood flow meter) were each measured for 5 h after induction of pancreatitis. The effect on renal hemodynamics of a new synthesized protease inhibitor--E-3123; 4-(2-succinimidoethylthio)phenyl-4-quanidinobenzoate methane sulfonate--intravenously infused at the rate of 3 mg/kg/h was also investigated. The mean blood pressure and pulse pressure decreased after induction of pancreatitis. Renal microcirculation and renal artery blood flow decreased during the experiment. However, in dogs with treated by E-3123, renal microcirculation was preserved during the first hour of the experiment and decreased gradually afterward, but it was significantly higher than that of the dogs without E-3123 during 3-5 h. The mean blood pressure and pulse pressure were preserved nearly at preoperative levels during the experimental period. We concluded that renal microcirculation decreased concomitantly with a deterioration of acute pancreatitis, and that the new pancreatic protease inhibitor E-3123 may have some beneficial effect to improve renal hemodynamics in the early period of acute pancreatitis.

Clinical outcomes of isolated renal failure compared to other forms of organ failure in patients with severe acute pancreatitis

“…The mechanisms of acute RF development in AP patients are not well studied and the resulting renal injury is likely multifactorial. Proposed mechanisms include hypoxemia-driven injury to the renal tubular epithelial cells[ 11 ], impairment of renal microcirculation due to released pancreatic amylase[ 12 ], release of apoptotic molecules including cytokines from the inflamed pancreas leading to renal cellular injury[ 13 ], and abdominal compartment syndrome that may develop in patients with SAP and lead to decreased renal perfusion pressure causing ischemic injury[ 14 ]. Accordingly, the favorable outcomes of patients with isolated RF, as shown in this study, could be a reflection of milder renal injury due to absence of hypoxemia when there is no associated respiratory failure.…”

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

“…Microcirculatory changes in early SAP are not confined to the pancreas, but are also well documented in other organs, i.e., colon and ileum, liver, lungs, kidneys, heart and brain [84,85,86,87]. In the early phase of organ failure due to SAP (only 3 h post induction of AP by taurocholate in rats), edema, leukocyte adhesion to capillary walls and infiltration in tissues were observed in histopathological examination of liver, kidney, lung, intestine, and spleen.…”

Disturbances of the microcirculation in acute pancreatitis

“…Changes to the microvascular circulation are not confined to the pancreas but may affect the gastrointestinal tract9, liver75, 86, lungs91, 92, kidney93 and skeletal muscle91. Abnormalities may be seen in the liver early in the course of disease86.…”