Fig. 1.

Induction of NOS2 mRNA in heart after LPS and identification of endotoxin-induced myocarditis in the RV. (A–D) A composite of film autoradiography showing the time course of NOS2 mRNA induction in the heart by in situ hybridization histochemistry. NOS2 mRNA induction starts at 2 h and progresses at 6 h after LPS administration. At 24 h, NOS2 levels return virtually to baseline in the LV, but are increased in the RV. (Scale bar = 2 mm.) (E–L)A composite of low-magnification (E, G, I, and K) and high-magnification (F, H, J, and L) images of NOS2 mRNA in heart ventricles. Shown are the LV at2h(E and F), 6 h (G and H), and 24 h (I and J) and the RV at 24 h (K and L). Arrows point to areas of increased NOS2 expression, which appear as white dots in dark-field (low magnification) and black dots in high-magnification images. Note high levels of NOS2 mRNA in the RV at 24 h (K and L). (Scale bar, 378 μm for E, G, I, and K and 30 μm for F, H, J, and L.) (M and N) Photomicrographs of hematoxylin/eosin-stained sections of heart ventricles 24 h after LPS administration. (M) In this section, the RV shows intense signs of inflammatory reaction. The myocardium is infiltrated by a moderate number of neutrophils that surround degenerate cardiomyocytes. Cardiomyocytes are fragmented, pale, and vacuolated, and in many areas the proteins are globular. Some globular proteins are surrounded by degenerate neutrophils characterized by fine nuclear debris and several neutrophils contain bright eosinophilic cytoplasmic material (phagocytosis). (N) Notice no signs of local inflammatory reaction in LV at 24 h after LPS administration. (Scale bar, 3.5 μm in M and 33.78 μm in N.)