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Published on: March 27, 2018
Activation of protein C and hemodynamic recovery after coronary artery bypass surgery
Peter Raivio1, Jose A Fernández, Anne Kuitunen
1Department of Cardiothoracic Surgery, Helsinki University Central Hospital, Helsinki, Finland. peter.raivio@hus.fi
Insights
Activated protein C (APC) levels dynamically balance thrombin generation during coronary artery bypass grafting. Higher APC levels during reperfusion correlate with better hemodynamic recovery, but preoperative APC levels indicate poorer outcomes.
Area of Science:
- Cardiovascular Science
- Hemostasis and Thrombosis
- Surgical Physiology
Background:
- Activated protein C (APC) is a key anticoagulant upregulated during coronary artery bypass grafting (CABG).
- The balance between thrombin generation and APC activation during CABG is not fully understood.
- Understanding this balance may reveal insights into hemodynamic recovery and myocardial damage.
Purpose of the Study:
- To investigate the dynamic relationship between thrombin generation and APC levels during CABG.
- To determine if APC activation during reperfusion correlates with postoperative hemodynamic recovery or myocardial damage.
Main Methods:
- Prospective study of 100 patients undergoing elective on-pump CABG.
- Serial measurements of APC, protein C, prothrombin fragment F1+2 (thrombin generation marker), and D-dimer (fibrinolysis marker).
- Hemodynamic parameters and postoperative cardiac biomarkers (creatine kinase, troponin T) were assessed.
Main Results:
- Reperfusion significantly increased thrombin generation, followed by a >3-fold increase in APC levels post-heparin neutralization.
- APC levels correlated with thrombin generation markers, but APC activation was delayed relative to thrombin generation during surgery and early reperfusion.
- Higher APC levels during early reperfusion were associated with improved postoperative cardiac index and lower systemic vascular resistance.
Conclusions:
- Reperfusion triggers significant thrombin generation, subsequently activating protein C.
- The dynamic balance between APC and thrombin significantly influences postoperative hemodynamic recovery after CABG.
Objectives:
Activated protein C is a physiologic anticoagulant that is activated by thrombin and upregulated during coronary artery bypass grafting. We studied the balance between thrombin generation and activated protein C levels during coronary artery bypass grafting and hypothesized that protein C activation during reperfusion is associated with hemodynamic recovery or postoperative myocardial damage.
Methods:
One hundred patients undergoing elective on-pump coronary artery bypass grafting were prospectively studied. Activated protein C, protein C, prothrombin fragment F1+2 (a marker of thrombin generation), and D-dimer (a marker of fibrinolysis) levels were measured preoperatively and at 7 time points during cardiopulmonary bypass and reperfusion and postoperatively. Hemodynamic parameters were measured serially. Cardiac biomarkers (mass of the Mb fraction of creatine kinase and troponin T) were measured postoperatively.
Results:
Reperfusion induced a significant increase in thrombin generation. Activated protein C levels peaked after heparin neutralization, when they increased more than 3-fold. Activated protein C levels correlated with F1+2 and D-dimer levels during cardiopulmonary bypass and reperfusion. Even though this correlation peaked during early reperfusion (r = 0.55, P < .001), the ratio of activated protein C to F1+2 decreased during surgical intervention and early reperfusion by 70% from the preoperative level, indicating a marked delay in protein C activation in relation to thrombin generation. Patients in the highest quintile of activated protein C levels during this period had a higher postoperative cardiac index (mean, 3.1 vs 2.5 L x min(-1) x m(-2); P < .05) and lower systemic vascular resistance (mean, 2137 vs 2429 dyne x s x cm(-5) x m(-2); P < .05). Conversely, levels of preoperative activated protein C and activated protein C measured after heparin neutralization were associated with unfavorable hemodynamic recovery postoperatively. Activated protein C or protein C levels were not associated with increased postoperative cardiac biomarkers.
Conclusions:
Reperfusion caused significant thrombin generation that was followed by activation of protein C. The balance of activated protein C with thrombin is associated dynamically with postoperative hemodynamic recovery.
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