1. CONCLUSION/ CLINICAL IMPLICATIONS REFERENCES/ACKNOWLEDGEMENTS
Effect of Losart­­an on Mast Cells in the Hearts of Rats Subjected to Fat Embolism
A. Fletcher1,2, A.M. Poisner2, S. Hamidpour1, C.Patel1, I. Choudry1, H. Pamulapati1, R. Ponnapureddy1, I. Greenberg1, S. Simon1, A. Molteni1
UMKC School of Medicine1, Kansas City, MO, 64108; University of Kansas Medical Center2, Kansas City, KS, 66160
INTRODUCTION
In a rat model of triolein-induced fat embolism (FE), administration of the angiotensin II type 1 receptor blocker- losartan (LOS) reduced the severe lung damage which develops up to 10 weeks post-triolein treatment1.2
Mast cells (MCs) are associated with the renin increase observed in the lungs in a model of brconchoconstriction3
FE damage is not limited to the lungs, and hearts of the same rats demonstrated severe histopathology which was also blocked by Los.4
Here we extend our investigation of the heart to the potential role of MCs in the pathogenesis of cardiovascular damage and how Los treatment effects MC count and distribution.
RESULTS
Severe vasculitis, perivascular fibrosis, and myocardial inflammation were present in the hearts of T treated rats vs saline controls. MCs were seen with a modest increase in T treated animals compared to the controls. The difference, however, was not statistically significant (20.8 +/- 5.3 vs /- 5.1: mean +/- STdev). Although Los markedly reduced the vasculitis and perivascular fibrosis, Los had no effect on MCs in the presence of absence of T. The results suggest that, although MCs are present in hearts of rats 10 weeks after T where vascular inflammation and histopathological damage is similar to that observed in the lungs, their number is more modestly increased and not affected by Los treatment.
Sal + Sal
T + Sal
“University of Missouri” changed to “UMKC School of Medicine” -JO
"1" made a superscript –JO
“Department of Pathology, Medicine, Biomedical and Health Informatics” and “Department of Preventative Medicine and Public Health, Pharmacology” removed and authors renumbered accordingly. –JO
“Results” title corrected to 32 font size –JO
Zip code not needed?-SB
Font for the title decreased from 36 to 32-SB
Font for affiliations increased from 28 to 32-SB
Sal + Los
T + Los
Figure 2. Representative samples of heart section with the four treatment groups stained with CD11 c-kit for MCs.
CONCLUSION/ CLINICAL IMPLICATIONS
Pulmonary fat embolism is complicated by myocardial damage in this model. The trend of an increase in MCs in the heart suggests a potential role of MCs in the pathogenesis of cardiovascular damage. The findings at this late time point, 10 weeks, after T may suggest different pathways or time course for histopathological changes compared to the lungs. It remains to be seen if the appearance of MCs in the heart after T is greater at earlier time points when the lung pathology is also greater.
METHODS
22 Sprague Dawley rats (~300 gm BW) received either T (0.2 mL i.v.) or saline. Six weeks later, half of the rats of each subgroup were given Los or saline. 4 weeks later (10 weeks post T injection), rats were euthanized with isoflurane and necropsied. Hearts were fixed in 10% formalin and stained with H&E (morphometric scoring), trichrome (fibrosis) and CD 11-c kit (MCs). On each heart slide, 10 photographs were taken at random at 400x and MCs counted by two pathologists unaware of the slide identity.
REFERENCES/ACKNOWLEDGEMENTS
A.M. Poisner et al. FASEB J : LB 512
A.M. Poisner et al. J. Trauma and Acute Surg Care
Veerappan et al. Proc Natl Acad Sci U.S.A. 2008:
Molteni A. et al. 18th International Colloquium On Lung and Respiratory Airways Fibrosis. Mont Tremblant Quebec Canada Sept 20-24, Proc of the meeting p. 95 
This work was supported by the Mary Katherine Geldmacher Research Foundation, St. Louis, MO
Sal + Sal T + Sal Sal + Los T + Los
Figure 1. Number of Mast Cells counted in the four treatment groups.