Activation of protein C and hemodynamic recovery after coronary artery bypass surgery

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 · min⁻¹· m⁻²; P < .05) and lower systemic vascular resistance (mean, 2137 vs 2429 dyne · s · cm⁻⁵· 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.

CTSNet classification: 23, 25

Abbreviations and Acronyms: AMI, acute myocardial infarction, ANOVA, analysis of variance, APC, activated protein C, CABG, coronary artery bypass grafting, CI, cardiac index, CK-Mbm, mass of the Mb fraction of creatine kinase, CPB, cardiopulmonary bypass, ICU, intensive care unit, PVRI, pulmonary vascular resistance index, SD, standard deviation, SVI, stroke volume index, SVRI, systemic vascular resistance index, TnT, troponin T