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Hemorrhagic Transformation After Large Cerebral Infarction in Rats Pretreated With Dabigatran or Warfarin

 Il Kwon  ;  Sunho An  ;  Jayoung Kim  ;  Seung-Hee Yang  ;  Joonsang Yoo  ;  Jang-Hyun Baek  ;  Hyo Suk Nam  ;  Young Dae Kim  ;  Hye Sun Lee  ;  Hyun-Jung Choi  ;  Ji Hoe Heo 
 Stroke, Vol.48(10) : 2865-2871, 2017 
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Animals ; Anticoagulants/administration & dosage ; Antithrombins/administration & dosage ; Cerebral Infarction/diagnostic imaging* ; Cerebral Infarction/drug therapy* ; Dabigatran/administration & dosage* ; Double-Blind Method ; Intracranial Hemorrhages/diagnostic imaging* ; Intracranial Hemorrhages/drug therapy* ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Warfarin/administration & dosage*
anticoagulants ; cerebral hemorrhage ; cerebral infarction ; dabigatran ; magnetic resonance imaging ; stroke ; warfarin
BACKGROUND AND PURPOSE: It is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is less frequent in dabigatran users than warfarin users. We compared the occurrence of HT after large cerebral infarction among rats pretreated with dabigatran, warfarin, or placebo. METHODS: This was a triple-blind, randomized, and placebo-controlled experiment. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or saline for 7 days, Wistar rats were subjected to transient middle cerebral artery occlusion. As the primary outcome, HT was determined by gradient-recalled echo imaging. For the secondary outcome, intracranial hemorrhage was assessed via gradient-recalled echo imaging in surviving rats and via autopsy for dead rats. RESULTS: Of 62 rats, there were 33 deaths (53.2%, 17 technical reasons). Of the intention-to-treat population, 33 rats underwent brain imaging. HT was less frequent in the dabigatran group than the warfarin group (placebo 2/14 [14%], dabigatran 0/10 [0%], and warfarin 9/9 [100%]; dabigatran versus warfarin; P<0.001). In all 62 rats, compared with the placebo (2/14 [14.3%]), the incidence of intracranial hemorrhage was significantly higher in the warfarin group (19/29 [65.5%]; P=0.003), but not in the dabigatran group (6/19 [31.6%]; P=0.420). Mortality was significantly higher in the warfarin group than the dabigatran group (79.3% versus 47.4%; P=0.022), but not related to the hemorrhage frequency. CONCLUSIONS: The risk of HT after a large cerebral infarction was significantly increased in rats pretreated with warfarin than those with dabigatran. However, the results here may not have an exact clinical translation.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
김영대(Kim, Young Dae) ORCID logo https://orcid.org/0000-0001-5750-2616
남효석(Nam, Hyo Suk) ORCID logo https://orcid.org/0000-0002-4415-3995
백장현(Baek, Jang Hyun)
유준상(Yoo, Joon Sang)
이혜선(Lee, Hye Sun) ORCID logo https://orcid.org/0000-0001-6328-6948
최현정(Choi, Hyun-Jung) ORCID logo https://orcid.org/0000-0003-3695-3420
허지회(Heo, Ji Hoe) ORCID logo https://orcid.org/0000-0001-9898-3321
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