Effect of nitric oxide in ischemia/reperfusion of the pancreas.
BACKGROUND
Ischemia/reperfusion injury, and thus graft pancreatitis, remains a major problem in pancreas transplantation. Contradictory results about the role of nitric oxide (NO) in pancreatic ischemia/reperfusion have been reported; however, in none of the reports has a detailed comparison between inhibition of NO synthase and NO supplementation been carried out.


METHODS
Vascular isolation of the pancreatic tail was performed in landrace pigs. After splenectomy catheters placed in the distal part of the splenic vessels allowed collection of the venous effluent and perfusion of the pancreatic tail. Three hours of complete warm ischemia was followed by 6 h of reperfusion. The effect of the NO donor sodium nitroprusside (SNP) and L-arginine was compared to a control group and NO synthase inhibition with L-NAME.


RESULTS
Lipase in the venous effluent of the pancreas was significantly decreased in the SNP and the L-arginine groups. Vascular resistance was markedly elevated in the L-NAME group and reduced in the NO donor groups. Tissue pO2 after reperfusion was only significantly elevated in the SNP group. Granulocyte infiltration and also overall histological tissue injury were most severe in the control group followed by the L-NAME group, the SNP group, and the L-ARG group.


CONCLUSIONS
The data show that supplementation of nitric oxide is clearly protective in pancreatic ischemia/reperfusion. However, inhibition of NO synthesis does not lead to an equally clear aggravation of tissue injury.
Department of Surgery, University of Freiburg, 79111 Freiburg, Germany.
S
S
Benz
R
R
Obermaier
R
R
Wiessner
P V
PV
Breitenbuch
D
D
Burska
H
H
Weber
R
R
Schnabel
Jens
J
Mayer
F
F
Pfeffer
H
H
Nizze
U T
UT
Hopt
D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008049:Lipase / Q000097:blood; D008833:Microcirculation; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010084:Oxidation-Reduction; D010092:Oximetry; D010101:Oxygen Consumption; D016035:Pancreas Transplantation; D010195:Pancreatitis / Q000378:metabolism* / Q000503:physiopathology* / Q000601:surgery; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D013552:Swine; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014655:Vascular Resistance
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D000255:Adenosine Triphosphate; D001120:Arginine; D008049:Lipase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester