title: Antithrombin-heparin covalent complex reduces microemboli during cardiopulmonary bypass in a pig model.
abstract: 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.
authors.affiliation: McMaster University, Hamilton, ON, Canada.
authors.forename: Petr
authors.initials: P
authors.lastname: Klement
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Berry
authors.forename: Peng
authors.initials: P
authors.lastname: Liao
authors.forename: Henry
authors.initials: H
authors.lastname: Wood
authors.forename: Paul
authors.initials: P
authors.lastname: Tressel
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Smith
authors.forename: Nihal
authors.initials: N
authors.lastname: Haque
authors.forename: Jeffery I
authors.initials: JI
authors.lastname: Weitz
authors.forename: Jack
authors.initials: J
authors.lastname: Hirsh
authors.forename: Nethnapha
authors.initials: N
authors.lastname: Paredes
authors.forename: Anthony K C
authors.initials: AK
authors.lastname: Chan
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004618:Embolism, Air / Q000175:diagnosis / Q000517:prevention & control*; D005260:Female; D006493:Heparin / Q000627:therapeutic use*; D034421:Sus scrofa; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D006493:Heparin