AN EXPERIMENTAL MULTIPLE-ORGAN MODEL FOR THE STUDY OF REGIONAL NET RELEASE UPTAKE RATES OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR IN THE INTACT PIG/

Experimental data indicate large between-organs variations in rates of synthesis of tissue-type plasminogen activator (t-PA), which may refl ect important differences in the capacity for constitutive and stimula ted t-PA release from the vascular endothelium. In this report we desc ribe a new multiple-organ experimental in vivo model for simultaneous determinations of net release/uptake rates of t-PA across the coronary , splanchnic, pulmonary, and hepatic vascular beds. In eleven intact a nesthetized Digs, blood samples were obtained simultaneously from the proximal aorta. coronary sinus, pulmonary artery, and portal and hepat ic veins. Plasma flows were monitored separately for each vascular reg ion. Total plasma t-PA was determined by ELISA with a porcine t-PA sta ndard. Regional net release/uptake rates were defined as the product o f arteriovenous concentration gradients and local plasma flows. The ne t release of t-PA across the splanchnic vascular bed was very high, wi th a mean output of 1,919 ng total t-PA X min(-1) (corresponding to 90 ng per min and 100 g tissue). The net coronary t-PA release was 68 ng X min(-1) (30 ng X min(-1) X 100 g(-1)). Pulmonary net fluxes of t-PA were variable without any significant net t-PA release. The net hepat ic uptake rate was 4,855 ng X min(-1) (436 ng X min(-1) X 100 g(-1)). Net trans-organ changes of active t-PA mirrored those of total t-PA. T he results demonstrate marked regional differences in net release rate s of t-PA in vivo. The experimental model we present offers new possib ilities for evaluation of regional secretion patterns in the intact an imal.