PMID- 20817849 OWN - NLM STAT- MEDLINE DCOM- 20110208 LR - 20210206 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 116 IP - 25 DP - 2010 Dec 16 TI - Antithrombin-heparin covalent complex reduces microemboli during cardiopulmonary bypass in a pig model. PG - 5716-23 LID - 10.1182/blood-2010-05-284448 [doi] AB - Transcranial Doppler-detected high-intensity transient signals (HITS) during cardiopulmonary bypass (CPB) surgery have been associated with postoperative neurocognitive dysfunction, suggesting microemboli in the brain could be a contributing factor. HITS occur despite administration of unfractionated heparin (UFH). This study was done to determine whether antithrombin-heparin covalent complex (ATH), a more potent anticoagulant than heparin, can reduce HITS during CPB. In a pig CPB model, ATH, UFH, or UFH + antithrombin (AT) was intravenously administered to female Yorkshire pigs after sternotomy. Twenty minutes later, hypothermic CPB was initiated and continued for 1.25 hours, then normothermia was re-established for 45 minutes. Protamine sulfate was given to neutralize the anticoagulants, and pigs were allowed to recover. HITS were monitored using an arterial flow probe placed over the carotid artery. Compared with UFH (300 or 1000 U/kg), ATH reduced the number of HITS during CPB in a dose-dependent manner. AT (3 mg/kg) + UFH (300 U/kg) resulted in an intermediate HITS rate between UFH and ATH (2 mg/kg in terms of AT). Examination of brain sections for emboli formation confirmed that, similar to HITS, number of thrombi decreased in direct proportion to ATH dosage. These results support the hypotheses that the majority of HITS represent thromboemboli and that ATH reduces emboli formation during CPB. FAU - Klement, Petr AU - Klement P AD - McMaster University, Hamilton, ON, Canada. FAU - Berry, Leslie R AU - Berry LR FAU - Liao, Peng AU - Liao P FAU - Wood, Henry AU - Wood H FAU - Tressel, Paul AU - Tressel P FAU - Smith, Lesley J AU - Smith LJ FAU - Haque, Nihal AU - Haque N FAU - Weitz, Jeffery I AU - Weitz JI FAU - Hirsh, Jack AU - Hirsh J FAU - Paredes, Nethnapha AU - Paredes N FAU - Chan, Anthony K C AU - Chan AK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100903 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Anticoagulants) RN - 0 (Antithrombins) RN - 9005-49-6 (Heparin) SB - IM MH - Animals MH - Anticoagulants/*therapeutic use MH - Antithrombins/*therapeutic use MH - Blood Coagulation/drug effects MH - Brain/drug effects/pathology MH - Cardiopulmonary Bypass/*adverse effects MH - Embolism, Air/diagnosis/*prevention & control MH - Female MH - Heparin/*therapeutic use MH - Sus scrofa MH - *Ultrasonography, Doppler, Transcranial EDAT- 2010/09/08 06:00 MHDA- 2011/02/09 06:00 CRDT- 2010/09/07 06:00 PHST- 2010/09/07 06:00 [entrez] PHST- 2010/09/08 06:00 [pubmed] PHST- 2011/02/09 06:00 [medline] AID - S0006-4971(20)60368-8 [pii] AID - 10.1182/blood-2010-05-284448 [doi] PST - ppublish SO - Blood. 2010 Dec 16;116(25):5716-23. doi: 10.1182/blood-2010-05-284448. Epub 2010 Sep 3.