Protective role of heme oxygenase-1 in pancreatic microcirculatory dysfunction after ischemia/reperfusion in rats.
OBJECTIVE
Microcirculatory derangements caused by ischemia and reperfusion (I/R) play a pivotal role in acute and graft pancreatitis. The inducible enzyme heme oxygenase 1 (HO-1) has been shown to decrease I/R injury by modulation of capillary perfusion in other organs. It was the aim of this study to evaluate the effect of HO-1 induction on pancreatic microcirculation after I/R.


METHODS
Rats were randomized into 4 groups: (1) sham controls; (2) 1-hour ischemia and 2-hour reperfusion (I/R); (3) I/R + cobalt protoporphyrin (CoPP), an HO-1 inducer; and (4) I/R + CoPP + tin protoporphyrin, an HO inhibitor. Functional capillary density (FCD) and leukocyte endothelium interaction were analyzed using intravital microscopy during reperfusion. Expression of HO-1 mRNA, HO-1 protein, and HO activity were assessed by Northern blot, Western blot, and an HO activity assay.


RESULTS
Functional capillary density decreased significantly in the I/R group as compared with sham controls. Cobalt protoporphyrin treatment increased FCD to control values. In contrast, HO inhibition in CoPP-pretreated animals lowered FCD and increased leukocyte endothelium interaction significantly. Cobalt protoporphyrin administration increased HO-1 mRNA, protein, and HO activity, whereas activity of the enzyme was reduced after injection of tin protoporphyrin.


CONCLUSIONS
Heme oxygenase 1 plays a beneficial role in pancreatic microcirculatory derangements after I/R. This could be of therapeutic relevance after pancreas transplantation and other forms of postischemic pancreatitis.
von Dobschuetz
Ernst
E
Department of General and Visceral Surgery, University Medical Center, Freiburg, Germany.
Schmidt
Rene
R
Scholtes
Moritz
M
Thomusch
Oliver
O
Schwer
Christian I
CI
Geiger
Klaus K
KK
Hopt
Ulrich T
UT
Pannen
Benedikt H J
BH
D000818:Animals; D002196:Capillaries / Q000201:enzymology; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D010179:Pancreas / Q000098:blood supply*; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology*; D011524:Protoporphyrins / Q000633:toxicity; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology*
D011524:Protoporphyrins; D012313:RNA; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1