Induction of biphasic changes in perfusion heterogeneity of rat liver after sequential stress in vivo

• Published in: Shock (Augusta, Ga.) Ga.), 2005-10, Vol.24 (4), p.324-331
• Main Authors: KAMOUN, Walid S, SHIN, Min C, KELLER, Steve, KARAA, Amel, HUYNH, Toan, CLEMENS, Mark G
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Anxiety disorders. Neuroses; Automation; Biological and medical sciences; Blood Flow Velocity; Cell Survival; Endothelin-1 - metabolism; Erythrocytes - cytology; Femur - pathology; Fracture Healing; Image Processing, Computer-Assisted; Intensive care medicine; Liver - blood supply; Liver - metabolism; Liver - pathology; Liver - physiology; Liver Circulation; Liver, biliary tract, pancreas, portal circulation, spleen; Male; Medical sciences; Microcirculation; Perfusion; Post-traumatic stress disorder; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; Sepsis; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Time Factors; Wound Healing
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/01.shk.0000180618.98692.ee

Trauma and subsequent sepsis lead to hepatic microcirculation disruption through various molecular mechanisms in which endothelin-1 (ET-1) plays a pivotal role. These stresses are thought to alter hepatic perfusion, heterogeneously leading to a mismatch of oxygen supply and demand. We hypothesize that mild remote stresses prime the liver to sequential sepsis through direct effects on the hepatic lobular flow distribution. We also propose to investigate the extent and the localization of the stress-induced microcirculation disruption. Sprague-Dawley rats were randomly divided into four experimental groups: sham, femur fracture (FFX), cecal ligation and puncture (CLP), and sequential stress (SS). Hepatic intravital microscopy was performed for in vivo assessment of the liver microcirculation flow distribution under baseline and after ET-1 infusion. Red blood cell motion distribution was used to quantify intralobular and interlobular heterogeneity of perfusion (HoP). Intralobular HoP, which reflects lobular regulation sites, was significantly increased in the FFX and CLP groups, but was not changed or decreased in the SS group compared with control. ET-1 infusion exerted opposite effects depending on the pathological condition, further increasing the difference between groups. SS induced decrease in intralobular HoP, contrasted with a significant increase in interlobular HoP, suggesting multiple disruption sites. Our data suggest that increased intralobular HoP may be indicative of a compensatory response to moderate stress; its decrease under sequential stress conditions corresponds with a total breakdown of hepatic lobular flow regulation. This may be another instance of the rich variability characteristic of normal physiology that "decomplexifies" under critical decompensated conditions.