Calcium administration augments pancreatic injury and ectopic trypsinogen activation after temporary systemic hypotension in rats.

Abstract

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.

• Authors: K Mithöfer, A L Warshaw, T W Frick, K B Lewandrowski, G Koski, D W Rattner, C Fernández-del Castillo
• Journal: Anesthesiology (Anesthesiology) Vol. 83 Issue 6 Pg. 1266-73 (Dec 1995) ISSN: 0003-3022 [Print] United States
• PMID: 8533919 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Trypsinogen
• Calcium

Topics

• Animals
• Blood Volume
• Calcium (administration & dosage, blood)
• Cardiopulmonary Bypass
• Enzyme Activation
• Hemorrhage (physiopathology)
• Hypotension (enzymology)
• Male
• Pancreatic Diseases (enzymology, etiology)
• Rats
• Rats, Sprague-Dawley
• Trypsinogen (metabolism)