In vivo release of tissue-type plasminogen activator antigen from the human brachial artery

Abstract

The rate of secretion of t-PA from vascular endothelial cells has been proposed as a good marker of endothelial function. Our aim was to measure the rate of in vivo t-PA antigen release from the human brachial artery and not from the combined vascular pool of the upper extremity. In 10 healthy male volunteers, we have occluded the forearm by a sphygmomanometer cuff for 5–7 min in order to reduce the blood flow in the brachial artery. Arterial blood samples were taken from the cubital artery above the occlusion and from the contralateral artery that served as the control. The arterial t-PA antigen concentrations were significantly higher after forearm occlusion than in the non-occluded contralateral arteries: median 3.3 (range between first and third quartile 2.1–3.6) vs. 2.5 (2.0–3.2) ng/ml, p=0.03. The PAI-1 antigen concentrations did not change significantly: 6.9 (2.3–18.6) ng/ml in the contralateral artery vs. 5.4 (1.8–8.0) ng/ml after occlusion, p=0.09. The average forward blood flow in the distal 15 cm of the brachial artery that was measured by duplex ultrasound decreased from 107 (97–118) ml/min at baseline to 25 ml/min (19–33) ml/min during occlusion. The release rate of circulating t-PA antigen was calculated as the product of the increment in arterial t-PA concentration and the average plasma flow in the arterial segment of interest with a volume of 2 ml. The median release rate of t-PA antigen under conditions of reduced blood flow in the brachial artery was 3.3 (1.1–11.5) ng/min. We conclude that the secretion of t-PA antigen from arterial endothelium of healthy subjects is substantial, whereas the arterial wall is not an important source of PAI-1 in vivo.