Microcirculatory function and tissue damage is improved after therapeutic injection of bovine hemoglobin in severe acute rodent pancreatitis.
OBJECTIVE
Stasis of the pancreatic microcirculation initiates and aggravates acute pancreatitis. Bovine hemoglobin has been shown to improve microcirculation in acute pancreatitis if prophylactically infused 15 minutes after initiation of acute pancreatitis. The purpose of this study was to evaluate the therapeutic effectiveness of bovine hemoglobin on pancreatic microcirculation and tissue damage later in the course of experimental acute rodent pancreatitis.


METHODS
In Wistar rats, severe acute pancreatitis was induced by administration of glyco-deoxycholic-acid intraductally and cerulein intravenously. Pancreatic microcirculation was continuously monitored by intravital microscopy. Three hours after the initiation of acute pancreatitis, animals received either 0.8 mL bovine hemoglobin (Oxyglobin), hydroxyethyl starch (HES), or 2.4 mL 0.9% NaCl intravenously at random. After 6 hours, animals were killed, and histopathological damage of the pancreas was assessed using a validated histology score.


RESULTS
Pancreatic microcirculation assessed by leukocyte adherence was significantly improved by the administration of bovine hemoglobin in comparison with normal saline over time (mean difference, 51.6 +/- 9.2; P < 0.001) and HES (mean difference, 24.1 +/- 9.2; P = 0.037). This result was paralleled by decreased tissue damage in the bovine hemoglobin group as opposed to NaCl (6.75 vs. 12; range, 5.25-7.75 vs. 8.25-14; P < 0.001) and HES (6.75 vs. 9; range, 5.25-7.75 vs. 7.5-10.75; P < 0.001).


CONCLUSIONS
Therapeutic intravenous infusion of bovine hemoglobin improves pancreatic microcirculation and reduces pancreatic tissue damage in severe acute rodent pancreatitis but is not as effective as early (prophylactic) administration.
Strate
Tim
T
Department of General Surgery, University Hospital Eppendorf, Martinistrasse 52, Hamburg, Germany. strate@uke.uni-hamburg.de
Mann
Oliver
O
Kleinhans
Helge
H
Rusani
Skelkim
S
Schneider
Claus
C
Yekebas
Emre
E
Freitag
Marc
M
Standl
Thomas
T
Bloechle
Christian
C
Izbicki
Jakob R
JR
D000208:Acute Disease; D000818:Animals; D002417:Cattle; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007962:Leukocytes / Q000473:pathology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D010179:Pancreas / Q000098:blood supply* / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D006454:Hemoglobins