Cardiopulmonary bypass and activation of antithrombotic plasma protein C.
OBJECTIVE
We hypothesized that antithrombotic plasma-activated protein C plays a defensive antithrombotic role during coronary ischemia and postischemic reperfusion.


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.
Petäjä
J
J
Children's Hospital, University of Helsinki, Finland. jari.petaja@dlc.fi
Pesonen
E
E
Fernández
J A
JA
Vento
A E
AE
Rämö
O J
OJ
Griffin
J H
JH
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D002314:Cardioplegic Solutions / Q000494:pharmacology; D002315:Cardiopulmonary Bypass / Q000379:methods; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology; D001026:Coronary Artery Bypass / Q000379:methods*; D005343:Fibrinolytic Agents / Q000276:immunology / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000601:surgery; D010422:Pentanones / Q000494:pharmacology; D011486:Protein C / Q000276:immunology / Q000378:metabolism*; D017293:Protein S / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D002314:Cardioplegic Solutions; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D005343:Fibrinolytic Agents; D010422:Pentanones; D011486:Protein C; D017293:Protein S; D005344:Fibrinopeptide A; C057364:nitecapone