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Aliskiren Does Not Protect the Heart from the Acute Histopathological Effects of Fat Embolism when it Protects the Lungs
Author(s) -
Ponnapureddy Rakesh,
Poisner Alan,
Fletcher Amanda,
Patel Chirag,
Tappeta Kathyayini,
Fotouhi Ariana,
Molteni Agostino
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.977.5
Subject(s) - aliskiren , medicine , losartan , renin–angiotensin system , fibrosis , masson's trichrome stain , lung , renin inhibitor , endocrinology , angiotensin ii , receptor , blood pressure
Introduction Fat embolism (FE) can lead to both acute and chronic lung injury. In an animal model of FE induced by Triolein, the histopathological damage was not limited to the lungs but also involved the heart and kidneys. We have previously demonstrated that losartan, an angiotensin receptor blocker, prevented the damage induced by FE in both the lungs and the heart at 10 weeks. We also identified significant pulmonary damage as early as 48 hours and it was prevented by the direct renin inhibitor, Aliskiren suggesting the role of Renin‐Angiotensin System (RAS) in the pathogenesis of fibrosis. In the current study we examined the acute effects of FE (48 hours) on the heart, the influence of Aliskiren on this organ and compared it to the effects on the lungs. Methods Twenty‐two rats were divided into controls (n=4, Group A) and three FE groups (n=6, Groups B, C & D). FE induction was done with Triolein 0.2 mL i.v. at 0 hours, and an hour later the animals received 0.2 ml i.p. saline (Groups A&B), Aliskiren at 50 mg/kg (Group C) or at 100 mg/kg (Group D). Rats were euthanized at 48 hours and hearts were fixed and stained with H&E for lumen patency measurements, Masson's Trichrome (MT) for collagen, and alpha‐smooth muscle actin (SMA) for myofibroblasts. Results Rats in FE only group (group B) had higher percentage of SMA staining around the branches of the coronary arteries compared to the control group (A) (P<0.05). There were no significant differences in lumen patency, media‐adventitia ratios and MT staining among the four groups. Aliskiren at both doses (C & D) did not show a significant effect on SMA staining compared to FE only (B). In contrast, Aliskiren at both doses showed reduction in SMA and MT staining in the Lungs. Conclusion Animals subjected to FE sustained acute injury (48 hours) of both the heart and the lungs, with less prominent changes in the heart. While Aliskiren significantly reduced the fibrotic damage in the lungs, such effect was not seen in the hearts of the same animals. This is in contrast to the delayed effects of FE at 10 weeks when there was similar extent of damage to both organs and protection by AT1 blocker losartan. These varying results suggest different pathophysiological processes in the evolution of the fibrosis in the two organs. Support or Funding Information Mary Katherine Geldmacher Research Foundation, St. Louis, MO