Impaired myocardial t-PA release in patients with coronary artery disease.
OBJECTIVE
Myocardial ischemia remains a significant perioperative complication in coronary artery disease (CAD) patients. We hypothesized that noxious stimuli during major surgery are associated with an acute release of tissue-type plasminogen activator (t-PA) into the coronary circulation, and that this response is reduced by CAD.


RESULTS
Two patient groups, with (n=14) and without (n=8) CAD, were studied during the initial phase of heart surgery. After retrograde great cardiac vein catheterizations during closed-chest conditions, coronary arterial-venous concentration gradients of t-PA and plasminogen activator inhibitor type-1 (PAI-1) were measured together with coronary blood flow measurements, allowing derivation of coronary net release rates. Pre-surgery atrial pacing, performed to evaluate the influence of increases in heart rate (+ 40 beats/min) and coronary blood flow (+ 80 ml/min), did not significantly alter coronary net release of t-PA or PAI-1 in either patient group. Sternotomy induced a prominent increase in coronary net release of both total and active t-PA in the non-CAD group. This response was considerably reduced in the CAD group.


CONCLUSIONS
This study provides the first analysis of coronary t-PA release during major surgery and demonstrates a deficient local endothelial t-PA release in patients with CAD. This suggests a reduced local fibrinolytic capacity in CAD patients, which may explain the increased risk for coronary thrombosis in this patient group.
Osterlund
B
B
Surgical and Perioperative Science, Anesthesiology and Intensive Care, Umeå University, Umeå, Sweden. barbro.osterlund@vll.se
Jern
S
S
Jern
C
C
Seeman-Lodding
H
H
Ostman
M
M
Johansson
G
G
Biber
B
B
D000368:Aged; D001794:Blood Pressure; D002304:Cardiac Pacing, Artificial / Q000379:methods; D006348:Cardiac Surgical Procedures / Q000379:methods; D002407:Catheterization, Swan-Ganz; D003324:Coronary Artery Disease / Q000378:metabolism*; D003328:Coronary Thrombosis / Q000517:prevention & control; D003331:Coronary Vessels / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000097:blood*
D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator