Endothelial release of tissue-type plasminogen activator and ischemia-induced vasodilatation are linked in patients with coronary heart disease

Dysfunction in the vascular endothelium disturbs blood flow and predisposes individuals to atherosclerosis. Deteriorated fibrinolysis may further enha nce the risk for atherothrombosis. We investigated 14 healthy volunteers an d 24 patients with coronary heart disease. Endothelium-dependent (acetylcho line- and ischemia-induced) and endothelium-independent (nitroprusside-indu ced) vasodilatation in the forearm vasculature were studied using strain-ga uge plethysmography, and the fibrinolytic system measured as the response o f tissue plasminogen activator (t-PA) to provocation testing (20 min venous occlusion; VOT). When acetylcholine-induced vasodilatation was measured, e ndothelium-dependent vasodilatation differed between groups: those with cor onary heart disease had a median value of 8.5 ml/min per 100 g tissue (25th to 75th percentile 4.8-10.3), compared with 11.6 ml/min per 100 g tissue ( 7.3-15.5) among healthy volunteers (P = 0.03). However, ischemia-induced va sodilatation showed no difference between the groups [26.8 (22.7-35.0) vers us 29.1 (25.6-30.7) ml/min per 100 g- tissue, respectively, NS]. Levels of t-PA after VOT also showed no difference between the groups [21.5 (16.5-31. 9) versus 20.4 (11.8-31.5) ng/ml, respectively, NS]. Results of ischemia te sts and levels of t-PA after VOT correlated only in patients with coronary heart disease (r = 0.5, P = 0.015), and not in healthy volunteers. We obser ved a positive correlation between endothelium-dependent vasodilatation fun ction and endothelial release of t-PA. This indicates that the same mechani sm that results in defective ischemia-induced endothelial relaxation in pat ients with coronary heart disease may also result in suppressed fibrinolyti c capacity, thus making such patients more prone to atherothrombosis. Blood Coag Fibrinol 10:181-187 (C) 1999 Lippincott Williams & Wilkins.