CALCIUM ADMINISTRATION AUGMENTS PANCREATIC INJURY AND ECTOPIC TRYSINOGEN ACTIVATION AFTER TEMPORARY SYSTEMIC HYPOTENSION IN RATS

Background: Calcium infusion and hypotension have been described as th e most important risk factors for pancreatic injury after cardiopulmon ary bypass. Methods: Rats were randomly allocated to three experimenta l groups undergoing either sham operation and saline infusion (Control , n = 30), hemorrhagic reduction of mean arterial pressure to 30 mmHg for 30 min alone (hypotension, n = 51), or hypovolemic hypotension fol lowed by bolus infusion of CaCl2 (200 mg . kg(-1); hypercalcemia, n = 85), Serum ionized calcium, amylase activity, trypsinogen activation p eptide in pancreatic tissue homogenates, pancreatic wet/dry weight rat io, histologic changes, and mortality were assessed for 24 h. Results: Control rats showed no significant changes of any parameter throughou t the experiments. In contrast, hypotension significantly increased se rum amylase (P < 0.001), tissue trypsinogen activation peptide (P < 0. 01), wet/dry weight ratio (P < 0.001), and histologic scores for edema (P < 0.001) and pancreatic necrosis (P < 0.05), Subsequent CaCl2 admi nistration transiently increased [Ca2+] (P < 0.001) with the concentra tion rapidly returning to baseline within 3 h. That infusion of CaCl2 further increased amylase (P < 0.05), tissue trypsinogen activation pe ptide (P < 0.05), wet/dry weight ratio (P < 0.001), and histologic evi dence of pancreatic edema (P < 0.05) and acinar necrosis (P < 0.05) wh en compared with hypotension alone. Whereas all Control animals surviv ed the experiments, 22% (P < 0.05) and 47% (P < 0.05 vs. hypotension) of animals died in the hypotension and hypercalcemia groups, respectiv ely. Conclusions: Temporary hypotension alone causes ectopic trypsinog en activation and lethal acute pancreatitis. Superimposed hypercalcemi a significantly aggravates hypotension-induced pancreatic injury and m ortality in rats.