TY - JOUR
T1 - Atrial natriuretic peptide reduces hepatic ischemia-reperfusion injury in rabbits
AU - Yamada, Takashige
AU - Kotake, Yoshifumi
AU - Nagata, Hiromasa
AU - Takeda, Junzo
N1 - Funding Information:
The authors give their heartfelt thanks to Kazunori Kikuchi, M.D., Department of Pathology, Tsukuba Medical Center, who provided carefully considered feedback and valuable comments. The authors also acknowledge Michiko Yamamoto, B.A., for her technical assistance. This work was supported by The Ministry of Education, Culture, Sports, Science and Technology: Grant-in-Aid for Young Scientists (Grant number 19791088).
PY - 2013/12
Y1 - 2013/12
N2 - Purpose: Atrial natriuretic peptide (ANP) has been known to be protective against hepatic ischemia/reperfusion injury. The purpose of this study was to verify the hypothesis that ANP conserves microvascular circulation and reduces ischemia-reperfusion injury in the in vivo rabbit model. Methods: With IRB approval, 30 male Japanese white rabbits under pentobarbital anesthesia were studied. These animals were randomly assigned to the following three groups (n = 10 each): control, ANP, and sham group. Animals in the ANP group received continuous infusion of ANP at 0.1 μg/kg/min throughout the study period. Animals in control and ANP groups underwent 90 min of partial hepatic ischemia by clamping the right hepatic artery and portal vein. Descending aortic blood flow (AoF) was monitored with a transit-time ultrasound flowmeter. Hepatic tissue microvascular blood flow (HTBF) at both right (ischemic) and left (nonischemic) lobe was intermittently evaluated with the hydrogen clearance method. After 180 min of reperfusion, hepatic injury was determined with serum AST and ALT. Galactose clearance of reperfused right lobe was also measured as an indicator of hepatic metabolic function. Histopathological change and the number of apoptotic hepatocytes were also evaluated. Results: Systemic hemodynamic data including mean arterial pressure, heart rate, and AoF did not differ among the three groups during the study period. ANP attenuated ischemia-induced right HTBF decrease. ANP also suppressed histopathological degeneration, apoptosis, and decline in galactose clearance after reperfusion. Conclusions: ANP attenuated hepatic microvascular dysfunction and hepatocyte injury after reperfusion without significant hemodynamic change.
AB - Purpose: Atrial natriuretic peptide (ANP) has been known to be protective against hepatic ischemia/reperfusion injury. The purpose of this study was to verify the hypothesis that ANP conserves microvascular circulation and reduces ischemia-reperfusion injury in the in vivo rabbit model. Methods: With IRB approval, 30 male Japanese white rabbits under pentobarbital anesthesia were studied. These animals were randomly assigned to the following three groups (n = 10 each): control, ANP, and sham group. Animals in the ANP group received continuous infusion of ANP at 0.1 μg/kg/min throughout the study period. Animals in control and ANP groups underwent 90 min of partial hepatic ischemia by clamping the right hepatic artery and portal vein. Descending aortic blood flow (AoF) was monitored with a transit-time ultrasound flowmeter. Hepatic tissue microvascular blood flow (HTBF) at both right (ischemic) and left (nonischemic) lobe was intermittently evaluated with the hydrogen clearance method. After 180 min of reperfusion, hepatic injury was determined with serum AST and ALT. Galactose clearance of reperfused right lobe was also measured as an indicator of hepatic metabolic function. Histopathological change and the number of apoptotic hepatocytes were also evaluated. Results: Systemic hemodynamic data including mean arterial pressure, heart rate, and AoF did not differ among the three groups during the study period. ANP attenuated ischemia-induced right HTBF decrease. ANP also suppressed histopathological degeneration, apoptosis, and decline in galactose clearance after reperfusion. Conclusions: ANP attenuated hepatic microvascular dysfunction and hepatocyte injury after reperfusion without significant hemodynamic change.
KW - Atrial natriuretic peptide
KW - Ischemia-reperfusion
KW - Liver injury
KW - Tissue microvascular blood flow
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U2 - 10.1007/s00540-013-1643-3
DO - 10.1007/s00540-013-1643-3
M3 - Article
C2 - 23736823
AN - SCOPUS:84891484089
VL - 27
SP - 901
EP - 908
JO - Journal of Anesthesia
JF - Journal of Anesthesia
SN - 0913-8668
IS - 6
ER -