Thrombin generation during reperfusion after coronary artery bypass surgery associates with postoperative myocardial damage.
BACKGROUND
Cardiopulmonary bypass and coronary artery bypass grafting (CABG) result in significant thrombin generation and activation of fibrinolysis. Thrombin contributes to myocardial ischemia-reperfusion injury in animal studies, but the role of thrombin in myocardial damage after CABG is unknown.


OBJECTIVE
We measured thrombin generation and fibrin turnover during reperfusion after CABG to evaluate their associations with postoperative hemodynamic changes and myocardial damage.


METHODS
One hundred patients undergoing primary, elective, on-pump CABG were prospectively enrolled. Plasma prothrombin fragment F(1+2) and D-dimer were measured preoperatively and at seven time points thereafter. Mass of the Mb fraction of creatine kinase (Ck-Mbm) and troponin T (TnT) were measured on the first postoperative day.


RESULTS
Reperfusion induced an escalation of thrombin generation and fibrin turnover despite full heparinization. F(1+2) during early reperfusion associated with postoperative pulmonary vascular resistance index. F(1+2) at 6 h after protamine administration correlated with Ck-Mbm (r = 0.40, P < 0.001) and TnT (r = 0.44, P < 0.001) at 18 h postoperatively. Patients with evidence of myocardial damage (highest quintiles of plasma Ck-Mbm and TnT) had significantly higher F(1+2) during reperfusion than others (P < 0.002). Logistic regression models identified F(1+2) during reperfusion to independently associate with postoperative myocardial damage (odds ratios 2.5-4.4, 95% confidence intervals 1.04-15.7).


CONCLUSIONS
Reperfusion caused a burst in thrombin generation and fibrin turnover despite generous heparinization. Thrombin generation during reperfusion after CABG associated with pulmonary vascular resistance and postoperative myocardial damage.
Raivio
P
P
Department of Cardiothoracic Surgery, Helsinki University Central Hospital, FIN-00029 HUS, Helsinki, Finland. peter.raivio@hus.fi
Kuitunen
A
A
Suojaranta-Ylinen
R
R
Lassila
R
R
Petäjä
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000209:etiology; D011183:Postoperative Complications / Q000209:etiology; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000150:complications*; D013917:Thrombin / Q000096:biosynthesis*
D005337:Fibrin; D006493:Heparin; D013917:Thrombin