Platelet dynamics in the early phase of postischemic liver in vivo.
BACKGROUND
In liver surgery, ischemia/reperfusion injury occasionally leads to liver failure by activating Kupffer cells (KCs) and leukocytes. However, few reports have demonstrated a relationship between KCs and platelets in vivo. This study investigated the relationship between these cells using intravital microscopy.


METHODS
Male Wistar rats were divided into two groups: (1) KC+ group, receiving 1 mL saline; and (2) KC- group, intravenously injected with liposome-encapsulated dichloromethylene disphosphonate for elimination of KCs. At 48 h after administration, 20 min of total normothermic hepatic ischemia was induced. Rhodamine-6G-labeled platelets and sinusoidal alterations were monitored using intravital microscopy up to 120 min after reperfusion. P-selectin, accumulated leukocytes and morphological damage, and alanine aminotransferase were evaluated.


RESULTS
In the KC+ group, numbers of adherent platelets increased significantly within 30 min after reperfusion. Endothelial cells of sinusoids in which KCs were mainly located were destroyed and the sinusoids were significantly constricted after reperfusion. Conversely, in the KC- group, adherent platelets in sinusoids were suppressed, and sinusoidal perfusion, endothelial cell damage and serum alanine aminotransferase levels were significantly improved. P-selectin on sinusoidal endothelial cells was not observed up to 120 min after reperfusion in either group.


CONCLUSIONS
Adherent platelets appear to reflect activation of KCs and lead to leukocyte accumulation, resulting in sinusoidal perfusion disturbance and liver failure. Evaluation of adherent platelets in the microcirculation offers an important marker of hepatic injury.
Nakano
Yoritaka
Y
Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. nokochi3@md.tsukuba.ac.jp
Kondo
Tadashi
T
Matsuo
Ryota
R
Hashimoto
Ikuka
I
Kawasaki
Takuya
T
Kohno
Keisuke
K
Myronovych
Andriy
A
Tadano
Sosuke
S
Hisakura
Katsuji
K
Ikeda
Osamu
O
Watanabe
Motonobu
M
Murata
Soichiro
S
Fukunaga
Kiyoshi
K
Ohkohchi
Nobuhiro
N
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002450:Cell Communication; D004002:Clodronic Acid; D042783:Endothelial Cells / Q000502:physiology; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D018715:Microscopy, Video; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D014661:Vasoconstriction
D019007:P-Selectin; D004002:Clodronic Acid; D000410:Alanine Transaminase