Impaired myocardial t-PA release in patients with coronary artery disease

• AIMS: 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. METHODS AND 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.

Nyckelord

Aged

Blood Pressure

Cardiac Pacing

Artificial/methods

Cardiac Surgical Procedures/methods

Catheterization

Swan-Ganz

Coronary Artery Disease/*metabolism

Coronary Thrombosis/prevention & control

Coronary Vessels/metabolism

Endothelium

Vascular/secretion

Female

Heart Rate

Humans

Male

Middle Aged

Myocardial Ischemia/*metabolism

Plasminogen Activator Inhibitor 1/*blood

Tissue Plasminogen Activator/*blood

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)