title: Dabigatran treatment: effects on infarct size and the no-reflow phenomenon in a model of acute myocardial ischemia/reperfusion.
abstract: The no-reflow phenomenon occurs when an epicardial coronary artery is reopened following myocardial infarction, but portions of the intramural microvasculature fail to reperfuse. One potential mechanism for this is the presence of fibrin tactoids. In addition, some recent studies have suggested that dabigatran treatment may be associated with increased incidence of myocardial infarction. Our aim was to investigate the effect on myocardial infarct size and no-reflow in an acute model of ischemia/reperfusion. Anesthetized, open-chest rabbits were randomly assigned to receive dabigatran (Dab, 0.5 mg/kg bolus + infusion, 0.15 mg/kg/h, IV, n = 11) or vehicle (Veh, n = 11) 15 m before a 30-m coronary artery occlusion and during 2.5 h of the 3 h reperfusion procedure. At the end of the reperfusion period, infarct size (% risk zone) and no-reflow defect were measured. The ischemic risk zone (% of left ventricle) was similar in groups, 24 % in Dab and 25 % in Veh. Necrosis was neither reduced nor increased by Dab treatment; expressed as a percentage of the risk region, infarct size was 30 ± 4 % in Dab and 28 ± 5 % in Veh, p = 0.76. The extent of no-reflow was comparable, expressed either as a percent of the risk region (19 ± 3 %, Dab and 18 ± 3 %, Veh) or as a percent of the necrotic zone (67 ± 8 % Dab and 65 ± 10 % Veh). Dab treatment had no effect on heart rate or blood pressure. Dabigatran treatment did not prevent or ameliorate the no-reflow phenomenon, suggesting that fibrin does not play a major role in the development of microvascular obstruction. Dabigatran did not exacerbate myocardial infarct size.
authors.affiliation: The Heart Institute of Good Samaritan Hospital, 1225 Wilshire Blvd, Los Angeles, CA, 90017, USA, sharon.hale@netscape.com.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hale
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kloner
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D000069604:Dabigatran; D004195:Disease Models, Animal; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D054318:No-Reflow Phenomenon / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran