Intermittence of blood flow in liver sinusoids, studied by high-resolution in vivo microscopy

Abstract

Kupffer cell migration and leukocyte-vessel wall interactions cause temporary slowing and/or stoppage of blood flow through individual liver sinusoids. Such temporal heterogeneity of flow was quantified in anesthetized mice and rats. Video recordings of red blood cell flow in 44 networks containing 8-16 sinusoids each were analyzed for 5- to 10-min periods. Flow was graded "fast," "slow," "stopped," or "reversed" based on red blood cell velocity. The mean numbers of flow changes (between grades) per minute in zone 1 vs. zone 3 were 1.39 vs. 0.78 (mouse) and 1.25 vs. 0.09 (rat). The mean percentage of time for each flow grade differed significantly between zones 1 and 3 and between species. For example, fast flow was present in zone 1 sinusoids for 51% of the time in mice and for 74% in rats; in zone 3 the corresponding numbers were 76 and 95%. Flow stasis was present in zone 1 sinusoids for 19% of the time in mice and for 7% in rats; in zone 3 the corresponding numbers were 2 and 0%. Thus considerable intermittence of perfusion exists, and the flow conditions create very different microenvironments for hepatocytes in zone 1 vs. zone 3.

Initiation of remote hepatic injury in the rat: Interactions between Kupffer cells, tumor necrosis factor-?, and microvascular perfusion

“…Recently, MacPhee et al 19 described the normal perfusion of rat liver as being highly heterogeneous and suggested that such heterogeneity would increase during pathological conditions. Our results and those of Vollmar et al 31 support such a hypothesis.…”

“…34 Although such mechanisms were not directly tested, the results from the present study support the hypothesis that Kupffer cell activation along hepatic sinusoids may contribute to the development of hepatic microvascular perfusion heterogeneity. 18,19 Kupffer cells are located primarily in periportal regions of the liver lobule, regions that possess smaller and more tortuous sinusoids than those of pericentral regions. 35,36 With these apparent differences, one would have expected a predisposition for periportal regions to possess more extensive perfusion heterogeneity if Kupffer cells were, in fact, contributing to the increased perfusion heterogeneity.…”

“…17 Moreover, migration of Kupffer cells along hepatic sinusoids has fostered the premise that such behavior may contribute to increased heterogeneity of hepatic microvascular perfusion. 18,19 TNF-␣, a pleiotropic cytokine, is also released by activated Kupffer cells, and has been implicated as an important mediator of hepatic injury. 17,20 TNF-␣ induces parenchymal injury via both necrotic and apoptotic processes.…”

A numerical model for predicting hepatocytes ureagenesis and its related inborn enzyme deficiencies: case studies

“…The inlet concentration of ammonia was chosen based on previous reported experimental data [20]. Then, hepatocytes convert ammonia into urea.…”

Toxic waste or hormone? Carbon monoxide as a regulator of sinusoidal tone

“…The fact that others have reported heterogeneregulatory role. Morphological studies have identified unmyelinated nerve fibers in close proximity to stellate cells, which ity in blood flow using in vivo microscopy, 18 …”