The distribution of glutathione in the rat liver lobule.

A quantitative cytochemical method was developed for measuring the GSH (reduced glutathione) content of hepatocytes in different regions of the rat liver lobule. Use of this method enabled us to show that GSH is not evenly distributed within the rat liver lobule. The hepatocytes located within 100 micrometer of the central vein contain much less GSH than do those in other regions of the rat liver lobule. We suggest that this partially explains the peculiar susceptibility of these cells to electrophilic attack by toxic metabolites formed via the microsomal cytochrome P-450 system.     

Intrarenal distribution of renal blood flow in the rat.

Intrarenal blood flow distribution was studied with the simultaneous use of the 99Tc labelled frog erythrocyte (microsphere) and the radioactive 86Rb fractionation method in the rat. The amount of blood entering the outer cortex (99Tc labelled erythrocytes method) proved to be higher than one perfusing the outer cortex (86Rb method), whereas the amount of blood entering the inner cortex (99Tc method) was less than the amount perfusing the inner cortex and medulla (86Rb method). Hence a group of the preglomerular arterioles in the outer cortex contributes to the blood supply of the inner cortex, on the other hand a group of preglomerular arteries in the inner cortex participates in the postglomerular blood supply of the medulla. Changes in the renal circulation are, however, associated with altered distribution of postglomerular vascular segments supplied by some groups of preglomerular arterioles. From this it is concluded that the postglomerular vessels of the deeper cortical layers constitute a system which is not parallelly coupled but comprises both series- and parallel-coupled sections. The contribution of these sections appears to vary depending on the actual haemodynamic conditions.     

Numerical investigation of non-Newtonian microcirculatory blood flow in hepatic lobule

The circulation in the liver is unique at macroscopic and microscopic levels. At the macroscopic level, there is an unusual presence of portal and arterial inputs rather than a single arterial input. At the microscopic level, a series of microenvironments in the acinar system is essential in controlling the functional characteristics of hepatic parenchymal cells. Since the hemodynamics is much less studied in the multifunctional liver, an attempt is made to study the hepatic hemodynamics in a segment of a hepatic lobular structure, that is made up of high-pressure oxygenated arteriole, low-pressure nutrient-rich portal venule, fenestrated sinusoidal space and hepatic venule. Our goal is to dispel some of the myths of this complex vascular bed by means of finite volume blood flow simulation. Flow features like high-velocity gradients near the fenestrations, flow reversal and Dean vortices in the sinusoidal space are analyzed within the non-Newtonian framework. Since no distinct exact or numerical solutions are available for this complex vascular bed, the present simulated results are compared with the available clinical observations. Results revealed that the pressure plays a key role in hepatic blood flow.     

No gravity-independent gradient of blood flow distribution in dog lung

The existence of a major gravity-independent gradient of blood flow in lungs has recently been described based on single photon emission computed tomography after intravenous injection of radioactively labeled macroaggregates. We wanted to test this hypothesis of a major gravity-independent gradient in lung blood flow in experiments with direct measurement of macroaggregate distribution in the dog lung. In six anesthetized (4 prone spontaneously breathing, 2 mechanically ventilated) dogs we injected 111In-labeled albumin macroaggregates intravenously. We killed the dogs, removed, inflated, and froze the lower lobes. We sliced the lobes 1 cm thick and made gamma camera images of the slices. We then cut three or four slices in each lobe into two or three concentric layers and measured the radioactivity per gram of tissue in a well-type gamma counter. In three of the dogs we also labeled the red cells (99mTc) so that blood volume in each sample could be determined. The gamma camera images were acquired on a 64 X 64 matrix with 4 X 4 mm pixels. On the numeric printouts from the individual slices we made two or three concentric layers and calculated activity per pixel in each layer. Neither by the well counting nor by the pixel analysis of the gamma scans did we detect any gravity-independent distribution of blood flow. With the well counting the distribution was the same whether macroaggregate activity was expressed per gram of tissue or per gram of blood-free tissue. We conclude that by direct measurements no major gravity-independent gradient of pulmonary blood flow can be detected in dog lungs.     

The distribution of blood flow velocity in the terminal bed of the rat mesentery

Blood flow velocities in microvessels of the rat intestinal mesentery were determined by means of prism-grating method. Mean velocity values in arterioles were 1.9 +/- 0.1, in venules 1.2 +/- 0.2, in capillaries 0.82 +/- 0.06 and in arteriole-venule anastomoses 1.7 +/- 0.2 mm/s. These values do not vary significantly in arterioles with internal diameter from 23.2 to 6.9 mm and in venules from 7.2 to 28.2 mm. The most significant velocity changes appear in the passage of arterioles into capillaries (50%) and between capillaries and venules (40%).     

Cerebral blood flow and blood viscosity in patients with polycythaemia secondary to hypoxic lung disease.

Blood viscosity, cerebral blood flow (CBF) and cerebral oxygen carriage (CBF X arterial oxygen content) were measured in 12 patients with polycythaemia secondary to hypoxic lung disease. CBF and cerebral oxygen carriage were both significantly higher than in a comparative group of 20 patients with raised packed cell volumes and normal lung function. The patients with secondary polycythaemia then underwent venesection and their mean packed cell volume fell from 0.613 to 0.495. This led to a consistent reduction in blood viscosity, which fell by 44% at a low shear rate (0.67/s) and 33% at a high shear rate (0.91/s). CBF rose by 21% (p less than 0.01), but cerebral oxygen carriage did not significantly increase in the group as a whole. Four of the patients with secondary polycythaemia had complained of episodes of confusion before venesection, which improved considerably once the packed cell volume had been lowered. Headache was relieved in a further two patients and none of the subjects was adversely affected by venesection. It was not possible, however, to show a correlation between symptomatic improvement and an increase in cerebral oxygen carriage.     

Ibuprofen reduces ethchlorvynol lung injury: possible role of blood flow distribution.

The role of cyclooxygenase products in acute lung injury was determined by pretreatment of dogs with ibuprofen before injury with intravenous ethchlovynol (ECV). In animals given ECV only, lung injury resulted in extravascular lung water of 18.9 ml/kg after 2 h, which was significantly higher than the 14.8 ml/kg in the group pretreated with ibuprofen. The comparison of gravimetric and indicator-dilution measurements of edema fluid indicates that edema fluid could not be reliably detected after treatment with ibuprofen because of diversion of flow from injured areas. Venous admixture increased from 6% at baseline to 32% 120 min after ECV in the vehicle-pretreated group compared with an increase from 4% at baseline to 7% in the ibuprofen-pretreated group. The regression analysis of the relationship between venous admixture and extravascular lung water indicated that, at any level of edema, venous admixture was significantly less in the group treated with ibuprofen than in the untreated group. Measurement of plasma and bronchoalveolar lavage fluid indicated that ibuprofen inhibited cyclooxygenase activity without affecting lipoxygenase activity. These results suggest that in intact dogs ibuprofen has a protective effect on both pulmonary gas transfer and pulmonary edema formation in ECV-injured lungs, which is consistent with limiting blood flow to injured segments of the lung.