Oxygenation of the arterial wall is provided by diffusion of oxygen outward from the main vessel lumen and inward from the adventitial vasa vasorum. In a group of four Yucatan miniature pigs the oxygenation profiles across the superficial femoral arteries were recorded by polarographic oxygen microelectrodes. The profiles obtained suggested a relatively poorly oxygenated media (a trough value of approximately 25% that of the intimal oxygenation) with a progressive rise in oxygenation toward the intimal and adventitial surfaces. In four other survival experiments, occlusion of the adventitial vasa vasorum by flush ligation of the arterial branches that supply them resulted in the production of a focal, intimal hyperplastic lesion that was absent in control vessels (intimal to medial ratios [mean +/- SEM] of 0.053 +/- 0.008, n = 8, p < 0.001 and 0.013 +/- 0.001, n = 8, respectively). By electron microscopy this lesion was seen to be composed mainly of smooth muscle cells. This evidence would support the hypothesis that arterial wall hypoxia may be involved in the initiation of intimal hyperplasia. It is proposed that human atherosclerosis may be initiated by occlusion of the vasa vasorum and concomitant hypoxia.

Chronic liver disease (CLD) is associated with muscle wasting, reduced exercise tolerance and aerobic capacity (AC). Measures of AC determined with cardiopulmonary exercise testing (CPET) may predict survival after liver transplantation (LT), but the relationship with nontransplant outcomes is uncertain. In patients assessed for LT, we examined the relationship of CPET AC parameters with the severity of liver disease, nutritional state, and survival with and without LT. Patients assessed for elective first LT who underwent CPET and an anthropometric assessment at a single center were studied. CPET-derived measures of AC that were evaluated included the peak oxygen consumption (VO 2 peak) and the anaerobic threshold (AT). Three hundred ninety-nine patients underwent CPET, and 223 underwent LT; 45% of the patients had a VO 2 peak < 50% of the predicted value, and 31% had an AT < 9 mL/kg/minute. The VO 2 peak and AT values correlated with the Model for End-Stage Liver Disease score, but they more closely correlated with serum sodium and albumin levels. The handgrip strength correlated strongly with the VO 2 peak. Patients with impaired AC had prolonged hospitalization after LT, and nonsurvivors had lower AT values than survivors 1 year after transplantation (P < 0.05); this was significant in a multivariate analysis. One hundred seventy-six patients did not undergo LT; the 1-year mortality rate was 34.6%. The AT (P < 0.05) and VO 2 peak values (P < 0.001) were lower for nonsurvivors. In a multivariate analysis, AT was independently associated with nonsurvival. In conclusion, AC was markedly impaired in many patients with CLD. In patients who did not undergo transplantation, impaired AT was predictive of mortality, and in patients undergoing LT, it was related to postoperative hospitalization and survival. AC should be evaluated as a modifiable factor for improving patient survival whether or not LT is anticipated. Liver Transpl 20:54-62, 2014. V C 2013 AASLD.Received June 4, 2013; accepted September 30, 2013.Many patients with chronic liver disease (CLD) develop progressive impairment of their fitness and exercise capacity.1 The clinical significance of these changes is reflected by the close association of altered musculature and exercise capacity with the risk for major disease-related complications and mortality.2-8

tain crude hemostatic parameters showed that there was a Cirrhosis is associated with compromised hemostasis lesser derangement of platelet counts, clotting factors, and and coagulopathy during orthotopic liver transplantaantithrombin III (ATIII) in patients with PBC and primary tion (OLT). It has been suggested that hemostasis is betsclerosing cholangitis compared with chronic active hepatitis. ter preserved during OLT in primary biliary cirrhosis This group also required fewer blood components. Mallet et (PBC) than other cirrhotic states. The aim of this study al. 7 observed that patients with hepatocellular disease and was to compare coagulation and fibrinolysis in 15 paportal hypertension had a larger blood loss and were more tients with PBC with 31 patients with other liver disease prone to develop hyperfibrinolysis during orthotopic liver before and during OLT. Preoperatively, both groups had transplantation (OLT) than patients with cholestatic disease subnormal mean levels of prekallikrein, factor XIIa, antisuch as PBC. More conclusively, Palareti et al. 8 showed differthrombin III (ATIII), plasminogen, and a 2 -antiplasmin.ent transfusional needs and intraoperative coagulation and C1 esterase inhibitor and kallikrein inhibition in PBC fibrinolytic changes between PBC and other cirrhoses. If pawas higher than the normal range (P õ .01), but not in tients with PBC have hemostatic abnormalities different non-PBC. Non-PBC had lower median fibrinogen levels from those found in other liver disease at the time of OLT, and shorter euglobulin clot lysis times (ECLT) (P õ .05).there may be implications for the postoperative development Tissue plasminogen activator (tPA) antigen levels did of unwanted thrombotic complications, especially if antifinot differ between groups but were elevated from the brinolytic agents are used perioperatively. normal range, as were median thrombin-antithrombinThe aim of this study was to investigate coagulation and complexes (TAT). Plasminogen activator inhibitor (PAI)fibrinolytic activation in patients with PBC compared with activity was significantly higher in PBC (0.0041). Periopother chronic liver disease before and during OLT. Specific eratively in the PBC group during the early anhepatic markers of coagulation activation, thrombin-antithrombin phase of OLT, there was more thrombin generation, as complexes (TAT), contact factors, and their inhibitors were evidenced by higher TAT levels (P Å .0455) and less hymeasured. Fibrinolysis was assessed by measuring tPA antiperfibrinolysis with longer ECLTs. We hypothesize that gen, euglobulin clot lysis time (ECLT), D-dimers, a 2 -antiplasthere is a preserved capacity to generate thrombin and min, and PAI-1 activity. less fibrinolytic activation during the anhepatic phase of OLT, and we suggest that, in PBC, the use of antifi- Table 1. There were Cirrhosis reduces the ability of hepatocytes to synthesize 15 patients with PBC and 31 with cirrhosis due to other causes. functional hemostatic proteins. These include the clotting fac-There...

Objective-To evaluate the role of liver transplantation after paracetamol overdose.Design-Prospective study of consecutive candidates for transplantation and performance of transplantation over 18 months.Setting-Liver unit, King's College Hospital, London.Main outcome measures -Fulfilment of indicators of poor prognosis, selection for transplantation, transplantation, survival.