Protective effects of heparin on hepatic ischemia and reperfusion lesions in rabbits.
Because the role of heparin (HEP) in hepatic ischemia/reperfusion (I/R) injury is still not fully understood, we investigated the effects of treatment with HEP on hepatic I/R injury in rabbits. For I/R procedures, the portal vein and hepatic artery were occluded by a metallic clamp to promote ischemia. The clamp was removed after 30 minutes to allow reperfusion. Rabbits undergoing the I/R procedure were treated with HEP (100 U/kg) or saline solution 0.9% (SS). When compared with levels before I/R, the serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, levels were increased by the hepatic I/R procedure, among rabbits treated with SS or HEP. However, the increase in these enzymes was lower among rabbits treated with HEP. Histologic analysis of hepatic tissue of rabbits undergoing I/R and treated with SS showed marked lesions in the central lobule with significant inflammatory infiltration. In contrast, a significant reduction in lesions caused by I/R was observed in the livers of rabbits treated with HEP. After starting reperfusion, we visualized apoptotic cells with nuclear staining among rabbits submitted to I/R and treated with SS, but not those treated with HEP. These results suggested that HEP was able to attenuate hepatic lesions caused by I/R in the livers of rabbits.
Taha
M O
MO
Department of Surgery, Federal University of São Paulo, Escola Paulista de Medicina, São Paulo, Brazil. taha@uol.com.br
Gonçalves
P F Z R A
PF
Vidigal
R O G
RO
Sacchi
G P S
GP
Pinheiro
F G
FG
Brandão
L S G
LS
Feguri
S
S
Moraes-Filho
A M
AM
Ghadie
M M
MM
Magalhães
K G
KG
Simões
M J
MJ
Tersariol
I L S
IL
Monteiro
H P
HP
Oliveira-Júnior
I S
IS
Oliveira
I
I
Jurkiewicz
A
A
Caricati-Neto
A
A
D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy* / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008107:Liver Diseases / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D011817:Rabbits; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*
D005343:Fibrinolytic Agents; D006493:Heparin; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase