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

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2865-2871
Number of pages7
JournalStroke
Volume48
Issue number10
DOIs
Publication statusPublished - 2017 Oct

Bibliographical note

Funding Information:
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (HI08C2149) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2014R1A1A1005913).

Publisher Copyright:
© 2017 American Heart Association, Inc.

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Fingerprint Dive into the research topics of 'Hemorrhagic transformation after large cerebral infarction in rats pretreated with dabigatran or warfarin'. Together they form a unique fingerprint.

Cite this