Splanchnic Compartment Research Articles

Effects of endotoxin on isolated porcine liver: pressure-flow analysis

The peripheral vascular response to sepsis is characterized by a vasodilatation of the systemic arterial vessels. Pulmonary hypertension with an increase in resistance and back pressure to flow defined by pressure-flow (P-Q) relationships has been reported in experimental sepsis. We hypothesized that endotoxin can induce differential alterations in resistance and back pressure to flow in the liver venous and arterial beds. Ninety minutes after endotoxin administration in intact anesthetized pigs (n = 8), the liver was vascularly isolated and perfused. Steady-state P-Q relationships in both the portal vein (PV) and hepatic artery (HA) were generated at multiple outflow pressures (Pout; 0, 5, 10, and 15 mmHg) and compared with those obtained in control livers (n = 6). Extrapolated zero-flow pressure intercepts (Pback) and slopes of the P-Q relationships were obtained by least squares linear regression analysis. Endotoxemia increased PV Pback (P < 0.05), and Pback always exceeded Pout (P < 0.05) when the latter was raised. In contrast, in controls, no difference was observed between Pback and Pout when the latter was raised. Endotoxemia also increased the PV slope compared with control. Raising Pout from 0 to 15 mmHg decreased PV slope in the endotoxin group to a greater degree than in controls (P < 0.05). In the HA, endotoxin caused a decrease in slope but did not alter Pback. The simultaneous increase in the PV Pback and slope that occurs with endotoxemia decreases splanchnic venous return, pooling blood in the splanchnic compartment for a given total blood volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Histamine and histamine receptor antagonists in splanchnic compartments in schistosomal portal hypertension.

The type and distribution of histamine receptors in the portal circulation were studied in patients with schistosomal hypertension. At laparotomy, the umbilical, left gastric, splenic, and superior mesenteric veins were cannulated. Blood samples were drawn from the systemic circulation and from each vein for histamine assay. Portal pressures were then estimated in each vein. One group of patients received local injections of pheniramine p-aminosalicylate (H1-antagonist) in the four cannulated veins simultaneously. A second group received cimetidine (H2-antagonist), and a third group received a mixture of both drugs. Reestimation of portal pressures indicated that all treatments produced a significant drop in pressure in the four compartments. The highest drop was in the splenic vein after the H1-antagonist and in the gastric vein after the H2-antagonist. The histamine level was somewhat higher in the splenic compartment. These results suggest that both H1- and H2-receptors are present in the four portal compartments, but their distribution may not be uniform.

Splanchnic compartmentation in schistosomal portal hypertension

Twenty-five cases with portal hypertension of schistosomal origin taken at random were studied. The transumbilical portal pressure, the transsplenic portal pressure, the left gastric vein portal pressure, and the superior mesentric vein portal pressure were measured at the same time in each. The transumbilical portal pressure-transsplenic portal pressure gradient, the transumbilical portal pressure-left gastric vein portal pressure gradient; the transsplenic portal pressure-left gatric vein portal pressure gradient; the transumbilical portal pressure-superior mesenteric portal pressure gradient; the transplenic portal pressure-superior mesenteric portal pressure gradient; and the left gastric vein portal pressure-superior mesenteric portal pressure gradients were found to be of particular value in defining five different hemodynamic patterns or splanchnic compartments, especially when correlated with the changes in the splanchnic vasculature as demonstrated by transumbilical portography and splenoportography. The type of pattern and the clinicopathological stage were considered in the selection of the most appropriate surgical procedure to alleviate the portal hypertension and/or its consequences.

Direct Conversion of Testosterone to Dihydrotestosterone Glucuronide in Man*

Tritiated testosterone and [14C]dihydrotestosterone (DHT) were administered by constant iv infusion into five young and five elderly men undergoing diagnostic cardiac catheterization. The radioactivity concentrations of free and conjugated DHT in arterial and hepatic vein blood samples were then determined. The analysis of the 3H:14C ratio of free DHT in arterial and hepatic vein blood showed that in both groups, the 3H:14C ratio of free DHT was the same in arterial and hepatic vein blood, indicating that splanchnic tissue is not the source of blood DHT from testosterone. This is in agreement with data that the transfer constant across the liver ([rho]T-DHT SD) was undetectable. In both young and elderly men, a significant increase of the 3H concentration of DHT glucuronide in hepatic vein blood was observed, indicating that the splanchnic compartment could be the site of production of DHT glucuronide. The 3H:14C ratio of DHT glucuronide was much higher than that of free DHT in both groups, suggesting that DHT glucuronide is derived from the blood testosterone pool, and most of the DHT from testosterone seems to be conjugated before mixing with blood DHT. This study indicates that a large fraction of DHT produced in the liver from testosterone is efficiently conjugated or further metabolized, and this results in the lack of splanchnic production of free DHT in men.

The extrasplanchnic origin of blood dihydrotestosterone in elderly men

The splanchnic extraction and interconversion of testosterone (T) and dihydrotestosterone (DHT) were studied in 5 elderly men undergoing cardiac catheterization using a constant Infusion of [1,2- 3H] testosterone and [4- 14C] DHT. Metabolic clearance rate (MCR), splanchnic extraction (SE), splanchnic clearance (SC), extrasplanchnic clearance (ESC), transfer constant In blood ([P] BB T-DHT) and transfer constant across the liver ([P] BB T-DHT) were calc̀ulated. The MCR T was 675 ± 108 (mean ± SC) L/day and MCR DHT was 409 ± 68 L/day. SE T was 45.9 ± 7.0% and SE DHT was 18.5 ± 5.4%. When these values are compared with those recently reported by us for normal men, there is a 1 3 reduction in SE T and 1 2 reduction for SE DHT in elderly men. The calculated SC T and ESC T were 355 ± 72 L/day and 320 ± 86 L/day, respectively. SC DHT and ESC DHT were 145 + 48 L/day and 263 ± 77 L/day respectively, suggesting that a major fraction of DHT is metabolized in extrasplanchnic organs. No evidence for a net appearance of DHT by either mass or specific activity analysis in hepatic vein blood was observed indicating that the splanchnic compartment does not contribute DHT into the circulation either by de novp synthesis or via conversion from testosterone. This work indicates that conversion of testosterone to DHT in elderly men occurs entirely in extrasplanchnic tissue.