Microcirculatory changes in livers of mice infected with murine hepatitis virus. Evidence from microcorrosion casts and measurements of red cell velocity

Hepatitis has been considered, classically, as a diffuse hepatocellular necrosis, and little attention has been paid to the relationship of lesions to the microvasculature. In livers of mice ( Balbc J ) infected with murine hepatitis virus (MHV-3), microcorrosion casts showed spherical cavities where casting compound was unable to fill sinusoids. At 48 hr postinfection such “lesions” had a mean diameter of 83 μm ± 26 (SD) and their number/mm 2 (at the surface of casts) was 0.95 ± 1.3. Blind-ended sinusoids formed a distinct boundary between perfused and nonperfused areas, and concave impressions at their ends indicated cells blocking the lumen. In vivo microscopy of transilluminated livers in infected mice showed localized rounded areas without flow, corresponding to lesions seen in casts. RBC velocity measurements in sinusoids adjacent to lesions demonstrated that velocities fall from normal values to zero over a narrow border zone. Beginning with the most proximal sinusoid with visible flow and moving outward from the lesion to the second and third sinusoids, mean RBC velocities (μm/sec, ± SD) were 17.4 ± 6.7, 33.9 ± 8.7, 66.6 ± 27.3, respectively; this last value was not significantly different from velocities in normal liver (69.2 ± 30.6). Transmission electron microscopy of livers of infected mice confirmed the presence of sinusoidal lumens blocked by protruding lining cells, RBCs, platelets, swollen hepatocytes, and cellular debris. This study demonstrates that the lesions are focal in origin, microvascular blockage leading to gradually increasing necrosis in all directions.