Evidence for angiotensin mediation of the late histopathological effects of pulmonary fat embolism

Protection by losartan in a rat model

Alan Poisner, Devin Bass, Amanda Fletcher, Ashwin Jain, Janessa Pennington England, Mariah Gawlik Davis, Dauod Arif, Agostino Molteni

Research output: Contribution to journalArticle

Abstract

Purpose: In a model of fat embolism using triolein-treated rats, we have reported that the acute pulmonary histopathological changes at 48 hrs were ameliorated by the angiotensin AT1 receptor blocker losartan, the angiotensin converting enzyme inhibitor captopril, and the direct renin inhibitor aliskiren. Although much of the pathology had declined by 3 weeks, the changes persisted at 6 weeks. The purpose of the study was to extends the time course investigation to 10 weeks and to examines whether the fat embolism effects continue to be blocked by losartan when given at a late time period. Materials and Methods: Unanesthetized rats were challenged with i.v. triolein or saline. After 6 weeks, one group received saline or losartan i.p. and the losartan group also received losartan in the drinking water. At 10 weeks, the experiment was terminated. Results: Confirming previous results, the fat embolism group showed normal weight gain at 6 weeks without apparent distress and also appeared normal at 10 weeks. However, at 10 weeks the lungs showed inflammatory and fibrotic changes that were greater than those found at 6 weeks. These changes were reduced by losartan. Conclusions: These findings show that the effects of fat embolism continue to progress to 10 weeks after the initial insult with triolein. The fact that the protective effects of losartan treatment started at 6 weeks supports the involvement of the renin-angiotensin system in late as well as early stages of the histopathological changes following fat embolism. It also supports the use of angiotensin blockade in clinical situations even long after an initial trauma where fat embolism is suspected.

Original languageEnglish (US)
Pages (from-to)361-367
Number of pages7
JournalExperimental Lung Research
Volume44
Issue number7
DOIs
StatePublished - Aug 9 2018
Externally publishedYes

Fingerprint

Fat Embolism
Losartan
Angiotensins
Pulmonary Embolism
Rats
Fats
Triolein
Renin
Lung
Angiotensin Type 1 Receptor
Angiotensin Receptor Antagonists
Captopril
Pathology
Renin-Angiotensin System
Angiotensin-Converting Enzyme Inhibitors
Drinking Water
Weight Gain
Wounds and Injuries

Keywords

  • Angiotensin
  • fat embolism
  • fibrosis
  • Histopathology
  • losartan
  • lung
  • rat
  • renin-angiotensin system
  • triolein

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Evidence for angiotensin mediation of the late histopathological effects of pulmonary fat embolism : Protection by losartan in a rat model. / Poisner, Alan; Bass, Devin; Fletcher, Amanda; Jain, Ashwin; England, Janessa Pennington; Davis, Mariah Gawlik; Arif, Dauod; Molteni, Agostino.

In: Experimental Lung Research, Vol. 44, No. 7, 09.08.2018, p. 361-367.

Research output: Contribution to journalArticle

Poisner, Alan ; Bass, Devin ; Fletcher, Amanda ; Jain, Ashwin ; England, Janessa Pennington ; Davis, Mariah Gawlik ; Arif, Dauod ; Molteni, Agostino. / Evidence for angiotensin mediation of the late histopathological effects of pulmonary fat embolism : Protection by losartan in a rat model. In: Experimental Lung Research. 2018 ; Vol. 44, No. 7. pp. 361-367.
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AU - England, Janessa Pennington

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AU - Molteni, Agostino

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N2 - Purpose: In a model of fat embolism using triolein-treated rats, we have reported that the acute pulmonary histopathological changes at 48 hrs were ameliorated by the angiotensin AT1 receptor blocker losartan, the angiotensin converting enzyme inhibitor captopril, and the direct renin inhibitor aliskiren. Although much of the pathology had declined by 3 weeks, the changes persisted at 6 weeks. The purpose of the study was to extends the time course investigation to 10 weeks and to examines whether the fat embolism effects continue to be blocked by losartan when given at a late time period. Materials and Methods: Unanesthetized rats were challenged with i.v. triolein or saline. After 6 weeks, one group received saline or losartan i.p. and the losartan group also received losartan in the drinking water. At 10 weeks, the experiment was terminated. Results: Confirming previous results, the fat embolism group showed normal weight gain at 6 weeks without apparent distress and also appeared normal at 10 weeks. However, at 10 weeks the lungs showed inflammatory and fibrotic changes that were greater than those found at 6 weeks. These changes were reduced by losartan. Conclusions: These findings show that the effects of fat embolism continue to progress to 10 weeks after the initial insult with triolein. The fact that the protective effects of losartan treatment started at 6 weeks supports the involvement of the renin-angiotensin system in late as well as early stages of the histopathological changes following fat embolism. It also supports the use of angiotensin blockade in clinical situations even long after an initial trauma where fat embolism is suspected.

AB - Purpose: In a model of fat embolism using triolein-treated rats, we have reported that the acute pulmonary histopathological changes at 48 hrs were ameliorated by the angiotensin AT1 receptor blocker losartan, the angiotensin converting enzyme inhibitor captopril, and the direct renin inhibitor aliskiren. Although much of the pathology had declined by 3 weeks, the changes persisted at 6 weeks. The purpose of the study was to extends the time course investigation to 10 weeks and to examines whether the fat embolism effects continue to be blocked by losartan when given at a late time period. Materials and Methods: Unanesthetized rats were challenged with i.v. triolein or saline. After 6 weeks, one group received saline or losartan i.p. and the losartan group also received losartan in the drinking water. At 10 weeks, the experiment was terminated. Results: Confirming previous results, the fat embolism group showed normal weight gain at 6 weeks without apparent distress and also appeared normal at 10 weeks. However, at 10 weeks the lungs showed inflammatory and fibrotic changes that were greater than those found at 6 weeks. These changes were reduced by losartan. Conclusions: These findings show that the effects of fat embolism continue to progress to 10 weeks after the initial insult with triolein. The fact that the protective effects of losartan treatment started at 6 weeks supports the involvement of the renin-angiotensin system in late as well as early stages of the histopathological changes following fat embolism. It also supports the use of angiotensin blockade in clinical situations even long after an initial trauma where fat embolism is suspected.

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