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Cardiopulmonary bypass and activation of antithrombotic plasma protein C
J Petäjä1, E Pesonen, J A Fernández
1Children's Hospital, University of Helsinki, Finland. jari.petaja@dlc.fi
Insights
Activated protein C plays a protective role during heart surgery. Insufficient activation of protein C during ischemia may hinder post-surgery recovery and circulation.
Area of Science:
- Cardiovascular Science
- Hematology
- Biochemistry
Background:
- The protein C pathway is known for its antithrombotic properties.
- Its role during cardiac ischemia and reperfusion is not fully understood.
Purpose of the Study:
- To investigate the role of plasma-activated protein C in coronary ischemia and postischemic reperfusion.
- To test the hypothesis that activated protein C has a defensive antithrombotic function.
Main Methods:
- Assessed protein C activation in 20 patients during cardiopulmonary bypass and coronary reperfusion.
- Measured plasma levels of protein C and activated protein C.
- Stratified patients based on activated protein C levels post-reperfusion.
Main Results:
- Protein C levels decreased, while activated protein C levels and the activated protein C/protein C ratio increased significantly during reperfusion.
- Patients with lower activated protein C increases showed poorer cardiac output and hemodynamics.
- Increased activated protein C post-reperfusion indicated activation in ischemic beds.
Conclusions:
- The antithrombotic protein C pathway is activated during cardiopulmonary bypass, particularly after aortic unclamping.
- Suboptimal protein C activation during ischemia may negatively impact postischemic cardiac recovery.
Objective:
We hypothesized that antithrombotic plasma-activated protein C plays a defensive antithrombotic role during coronary ischemia and postischemic reperfusion.
Methods And Results:
We evaluated protein C activation during cardiopulmonary bypass and coronary reperfusion in 20 patients undergoing coronary bypass surgery. During cardiopulmonary bypass and during the 10 minutes after aortic unclamping, the plasma levels of protein C (mean +/- standard error of the mean) decreased from 123% +/- 7% to 74% +/- 5% of normal mean. In contrast, the levels of activated protein C in plasma increased from 122% +/- 8% to 159% +/- 21%, and the activated protein C/protein C ratio increased from 1.04 +/- 0.08 to 2.29 +/- 0. 31 (P =.006, 2-tailed Wilcoxon signed rank test). Patients were stratified on the basis of the increase in activated protein C in the coronary sinus plasma at 10 minutes after reperfusion by means of the arbitrary value of 1.5 for the activated protein C/protein C ratio. Within 24 hours, the patients with low increases in activated protein C (ratio < 1.5, n = 8) had a significantly (P <.05) lower cardiac output and mean pulmonary artery pressure, as well as a higher systemic vascular resistance, than patients (n = 11) with high increases in activated protein C (ratio > 1.5). The rapid increase in activated protein C during the first 10 minutes after aortic unclamping indicated protein C activation in the reperfused vascular beds.
Conclusions:
The antithrombotic protein C pathway was significantly activated during cardiopulmonary bypass mainly during the minutes after aortic unclamping in the ischemic vascular beds. Suboptimal protein C activation during ischemia may impair the postischemic recovery of human heart and circulation.