Objective: We investigated whether the timing of administration of contrast medium after onset of acute pancreatitis is critical in determining the magnitude of microcirculatory derangement.
Methods: An acute pancreatitis model in male Sprague-Dawley rats (225–275 g) was established by continuous infusion of cerulein (15 mg/kg per hour). The mean arterial pressure was monitored continuously by means of a femoral artery catheter. Diatrizoate (Hypaque-76), a water-soluble contrast medium, was delivered through a femoral vein catheter at doses corresponding to those given to humans, either 1, 2, or 3 hours after pancreatitis induction. In vivo microscopy and laser-Doppler flowmetry were used to investigate microcirculatory derangement. The water contents of the pancreas and lung, the malondialdehyde levels of the pancreas, and the trypsinogen activation peptide levels in the serum were measured at the end of the experiment (8 hours after infusion of cerulein).
Results: Early administration of contrast medium (1 hour after pancreatitis induction) resulted in significantly greater changes in microcirculation and mean arterial pressure than did late administration (2 or 3 hours after pancreatitis induction). Rats given contrast medium 1 hour after induction also had highest pancreas and lung water contents, the highest pancreas malondialdehyde levels, and the highest serum trypsinogen activation peptide levels.
Conclusion: These results show that a water soluble contrast medium that is often used for computed tomographic imaging of the pancreas can adversely affect the pancreatic microcirculatory parameters, such as tissue perfusion and leukocyte sticking, and hemodynamics in a cerulein-induced model of acute pancreatitis. Early administration seems to cause more severe derangement of the pancreatic microcirculation.
Acute pancreatitis remains a major challenge to gastroenterologists, surgeons, and physicians who provide intensive care. Progress in the understanding of the pathophysiology of acute pancreatitis has opened up new therapeutic possibility. 1–3 The initial events in the acinar cells are still unknown, but the subsequent changes in the pancreatic vasculature and dysfunction in various organs have been described in detail. 4,5 The microcirculatory changes in various organs in the patients with acute pancreatitis are now gaining attention as an important process in the progression of the disease, although the final pathway has not been fully defined. 6,7
Contrast-enhanced computed tomography (CECT) is a well-established diagnostic tool for differentiating perfused pancreatic tissue from pancreatic necrosis in the patients with acute pancreatitis. Lack of enhancement of a region of the pancreas on CECT correlates reliably with pancreatic necrosis found during surgery. 8,9 Because pancreatic necrosis is associated with infection complications and late mortality in patients with severe acute pancreatitis, CECT has become the standard procedure for evaluating the severity of acute pancreatitis and the need for surgical intervention. 10,11 However, emerging data suggest that the contrast media used in these studies may further damage the pancreas. 12,13 The adverse effects of contrast media on diseased endothelia are related to the chemotoxicity, osmotoxicity, ion toxicity, and dose of the contrast solution. 14 In this study, we tested the effects of timing of infusion of a water-soluble contrast medium that is frequently used in the CECT on pancreatic microcirculatory changes in an animal model of acute pancreatitis.
From the Department of Surgery (H.-M.C., C.-P.C., T.-Y.C., C.-C.L., M.-F.C.) and Anaesthesia (M.-H.S.), Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Taipei, Taiwan, Republic of China.
Address for reprints: Han-Ming Chen, Department of Surgery, Chang Gung Memorial Hospital 199, Tun-Hwa North Road, Taipei, Taiwan; email: firstname.lastname@example.org.
Submitted for publication June 23, 1999.
Accepted for publication December 30, 1999.
This work is supported by research grant NSC 88–2314-B182A-070 from the National Science Council, Taiwan.