TY - JOUR
T1 - Evidence for angiotensin mediation of the late histopathological effects of pulmonary fat embolism
T2 - Protection by losartan in a rat model
AU - Poisner, Alan
AU - Bass, Devin
AU - Fletcher, Amanda
AU - Jain, Ashwin
AU - England, Janessa Pennington
AU - Davis, Mariah Gawlik
AU - Arif, Dauod
AU - Molteni, Agostino
PY - 2018/8/9
Y1 - 2018/8/9
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.
KW - Angiotensin
KW - Histopathology
KW - fat embolism
KW - fibrosis
KW - losartan
KW - lung
KW - rat
KW - renin-angiotensin system
KW - triolein
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U2 - 10.1080/01902148.2018.1552339
DO - 10.1080/01902148.2018.1552339
M3 - Article
C2 - 30638089
AN - SCOPUS:85060041732
VL - 44
SP - 361
EP - 367
JO - Experimental Lung Research
JF - Experimental Lung Research
SN - 0190-2148
IS - 7
ER -