Distinct effects of surgical denervation on hepatic perfusion, bowel ischemia, and oxidative stress in brain dead and living donor porcine models

Abstract

The liver function and perfusion following brain death is mainly influenced by the sympathetic nerves and hormones. We examined the specific influence of surgical liver denervation on systemic and hepatic perfusion parameters, bowel ischemia and oxidative stress in hemodynamically stable BD and control (living donor [LD]) pigs. Brain death was induced in 8 pigs via saline infusion into the balloon of an epidural Tieman-catheter (1 mL/15 minutes) and compared to the control group (n ϭ 6) over 4 hours. At 2 hours postoperatively, complete liver denervation was initiated. We analyzed systemic cardiocirculatory parameters (mean arterial pressure, aortic flow, bowel ischemia (endotoxin, and endotoxin-neutralizing capacity) and oxidative stress (total glutathione in erythrocytes [tGSH E ]) and compared them to local/hepatic perfusion parameters (hepatic artery and portal venous flow, liver blood flow index, and microperfusion), local bowel ischemia (intramucosal pH [pHi] of stomach [pHi S ]/colon[pHi C ]), and liver oxidative stress (glutathione [rGSH L , GSSG L ]). Following brain death, the parameters including mean arterial pressure, aortic flow, pHi, endotoxin, and tGSH E showed no significant changes at 2 hours. Portal venous flow and microperfusion were decreased significantly and hepatic arterial buffer response was ineffective. Hepatic oxidative stress was increased in BD animals (2rGSH L , 1GSSG L ). Surgical denervation/manipulation increased portal venous flow significantly, hepatic arterial buffer response became effective, and stomach pHi decreased (BD and LD groups). Hepatic oxidative stress was reduced in the BD group (1rGSH L /GSSG L ; P Ͻ 0.001) while it was increased in the LD group (2rGSH L /GSSG L ; P Ͻ 0.001). In conclusion, denervation reduces hepatic oxidative stress in BD only in contrast to the LD. The reciprocal effect of denervation depends on the state of neural activation and postulates a potential benefit of surgical denervation before organ harvesting in brain death. Liver Transpl 13:607-617, 2007.

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

“…In addition to physiological conditions, the HABR has been described to be also maintained in cirrhotic livers of animals and humans (18,572,670) and after liver transplantation (286). Of interest, this response is lost upon brain death (236), under increased intraabdominal pressure (CO 2 pneumoperitoneum) (671), and during endotoxemia (25,262,708). The fact that NO (262,789) but also terlipressin (24) restore the HABR during endotoxemia reflects the temporal and spatial complexity in the misbalance of expression of vasoconstrictive and vasodilative mediators (see sect.…”

Anesthesia for Patients With Liver Disease

“…Stimulants of sympathetic activity such as inducing psychic stress in adult male mice, baroreceptor response, acute urinary retention, or inserting painful stimuli during anesthesia reduce regional hepatic blood flow (54, 55). In animal models of liver surgery and manipulation, hepatic denervation exerted differential effects on living compared to brain-dead animal models, which could possibly be related to altered sympathetic activity (56). …”

Feasibility and Effectiveness of a New Algorithm in Preventing Hepatic Artery Thrombosis after Liver Transplantation

“…22 The hepatic arterial buffer response is an intrinsic regulatory mechanism of the hepatic artery that compensates for reductions in portal venous blood flow by hepatic vasodilatation. In small grafts that are accompanied by an excessive portal inflow (>250 mL/min/100 g graft weight), perioperative ligation of the splenic artery may improve arterial flow.…”