Over a period of 10 years, the authors have systematically reduced portacaval H-graft diameters. Their objective was to achieve partial shunting of portal flow without reversal of hepatic flow. This report summarizes their clinical and hemodynamic observations in 68 surviving patients with cirrhosis (mostly alcoholic) and variceal hemorrhage who underwent portacaval H-grafts ranging from 20 to 8 mm diameters. When shunt diameters were reduced to 10 and 8 mm and combined with aggressive portal collateral ablation, portal pressures increased significantly over larger H-grafts. Only 3% of patients with 20-12 mm H-grafts had prograde portal flow after operation, compared with 46 and 82% after 10 and 8 mm H-grafts, respectively (p less than 0.001). The incidence of encephalopathy diminished from 39% in the 20-12 mm H-graft group to 19 and 9% after 10 and 8 mm grafts, respectively (p less than 0.04). None of the patients with 10 or 8 mm PTFE grafts rebled from varices in the follow-up period (4-61 months). It is concluded that partial shunting of portal flow is hemodynamically feasible. It can be achieved in most patients using 8 mm polytetrafluoroethylene (PTFE) portacaval H-grafts combined with portal collateral ablation. Preserving prograde portal flow by partial shunting correlates with reduced encephalopathy rates after operation. Despite maintaining a relatively hypertensive portal system, partial shunts effectively prevent variceal hemorrhage.

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Increased susceptibility to mucosal damage is a prominent feature of portal hypertensive gastropathy. Since the portal hypertensive gastric mucosa has extensive microvascular changes, we postulated that the increased sensitivity to mucosal damage could have an ischemic basis. We measured distribution of gastric serosal and mucosal oxygenation in a group of portal hypertensive and sham-operated rats, and then studied the effects of intragastric aspirin. In the basal state, gastric mucosa of portal hypertensive rats had significantly reduced oxygenation compared to controls (24 +/- 5 vs 45 +/- 7 mm Hg PO2, P less than 0.02), while serosal oxygenation was similar between the two groups. Intragastric aspirin produced significantly greater mucosal damage to portal hypertensive rats and mucosal oxygenation was almost one third that of sham-operated controls. Systemic arterial pressures and oxygenation were similar between the two groups. We conclude that there is impairment of gastric mucosal oxygenation and increased mucosal damage by aspirin in portal hypertensive rats compared with sham-operated controls. These results support our hypothesis that the increased sensitivity of the portal hypertensive mucosa to damage is a consequence of impaired mucosal oxygenation.

A B S T R A C T Hypertyraminemia is common in hepatic cirrhosis and correlates in severity with encephalopathy. The mechanism of cirrhotic hypertyraminemia has not been established. The alternative possibilities are increased production from tyrosine and impaired degradation by monoamine oxidase. This investigation determined the pharmacokinetics of tyramine after an intravenous bolus injection of [3H]-tyramine uCi,12 Ci/mmol sp act) in 13 cirrhotics and 9 controls. In normals, [3H]tyramine levels initially declined rapidly (a-phase) followed by a slower decline (,8-phase) with an average t1/2 of20.8 min. Average normal metabolic clearance rate and production rate were 13.2 liters/min and 15.4 ,ug/min, respectively.In cirrhotic patients, the plasma disappearance curve for [3H]tyramine was qualitatively similar to that of the control subjects with no apparent difference in _3-t1/2 (17.2 min). The hypertyraminemia of cirrhosis resulted primarily from overproduction of tyramine, as the production rate (32.0 ,Lg/min) in these patients was significantly greater (P < 0.05) than in controls, whereas the metabolic clearance rate remained normal (average 12.2 liters/min). A difference in ratio of tyramine metabolic products was noted as well. Cirrhotics had a high ratio of plasma 4-hydroxyphenylethanol:4-hydroxyphenylacetic acid (60:40 vs. 30:70) fects on circulatory and neurologic functions, which are often disturbed in cirrhotics (1-5). An understanding of the mechanism of the hypertyraminemia of cirrhotic patients is therefore desirable. The accumulation of tyramine in plasma could result from increased production, decreased degradation, or a combination of both effects.Tyramine is produced by decarboxylation of tyrosine (Fig. 1). Plasma tyrosine is elevated in cirrhotics (6-8), and tyrosine tolerance is impaired (9), therefore more tyrosine is available for tyramine formation than in normals. Tyramine is also produced in the gastrointestinal tract by bacterial decarboxylation of tyrosine and may enter the systemic circulation via portasystemic shunts.Tyramine is degraded by monoamine oxidase, of which the major proportion is located in the liver. Accordingly, tyramine degradation could be delayed in cirrhosis because ofhepatocellular disease, diminished hepatic blood flow, or both.In this study, we have measured the production rate and metabolic clearance rate of plasma tyramine in normals and in cirrhotics with a pharmacokinetic technique. The kinetics of tyramine were correlated with the clinical status of the liver patients, the fasting plasma tyrosine, and the tyrosine tolerance. A hypothesis relating hypertyraminemia and hypertyrosinemia was developed from the results. METHODS Materials[3H]Tyramine (11.6 Ci/mmol sp act) was obtained from New England Nuclear (Boston, Mass.). Radiochemical purity, evaluated by analytic thin-layer chromatography with three different solvent systems (10) SubjectsThe control group consisted of 11 healthy adult volunteers, 9 males and 2 females, with no history of hepatobiliary d...

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