Calcium administration augments pancreatic injury and ectopic trypsinogen activation after temporary systemic hypotension in rats.
BACKGROUND
Calcium infusion and hypotension have been described as the most important risk factors for pancreatic injury after cardiopulmonary bypass.


METHODS
Rats were randomly allocated to three experimental 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 followed by bolus infusion of CaCl2 (200 mg.kg-1; hypercalcemia, n = 85). Serum ionized calcium, amylase activity, trypsinogen activation peptide in pancreatic tissue homogenates, pancreatic wet/dry weight ratio, histologic changes, and mortality were assessed for 24 h.


RESULTS
Control rats showed no significant changes of any parameter throughout the experiments. In contrast, hypotension significantly increased serum 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 administration transiently increased [Ca2+] (P < 0.001) with the concentration rapidly returning to baseline within 3 h. That infusion of CaCl2 further increased amylase (P < 0.05), tissue trypsinogen activation peptide (P < 0.05), wet/dry weight ratio (P < 0.001), and histologic evidence of pancreatic edema (P < 0.05) and acinar necrosis (P < 0.05) when compared with hypotension alone. Whereas all Control animals survived the experiments, 22% (P < 0.05) and 47% (P < 0.05 vs. hypotension) of animals died in the hypotension and hypercalcemia groups, respectively.


CONCLUSIONS
Temporary hypotension alone causes ectopic trypsinogen activation and lethal acute pancreatitis. Super-imposed hypercalcemia significantly aggravates hypotension-induced pancreatic injury and mortality in rats.
Mithöfer
K
K
Department of Surgery, Massachusetts General Hospital, Boston 02114, USA.
Warshaw
A L
AL
Frick
T W
TW
Lewandrowski
K B
KB
Koski
G
G
Rattner
D W
DW
Fernández-del Castillo
C
C
D000818:Animals; D001810:Blood Volume; D002118:Calcium / Q000008:administration & dosage* / Q000097:blood; D002315:Cardiopulmonary Bypass; D004789:Enzyme Activation; D006470:Hemorrhage / Q000503:physiopathology; D007022:Hypotension / Q000201:enzymology*; D008297:Male; D010182:Pancreatic Diseases / Q000201:enzymology / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014362:Trypsinogen / Q000378:metabolism*
D014362:Trypsinogen; D002118:Calcium