Wayne L Chandler1, Tomas Velan. 1. Department of Laboratory Medicine, University of Washington, Box 357110, Seattle, WA 98195-7110, USA. wcl@u.washinton.edu
Abstract
INTRODUCTION: Cardiopulmonary bypass (CPB) is associated with elevated tissue plasminogen activator (t-PA) levels during CPB and increased plasminogen activator inhibitor 1 (PAI-1) levels post-operatively. The goal of this study was to estimate the rate of t-PA and PAI-1 secretion in vivo, before, during and after CPB. MATERIALS AND METHODS: Estimated rates of t-PA and PAI-1 secretion were based on measured levels of active and total t-PA, and active and total PAI-1, obtained before, during and after CPB from nine males, combined with a computer model of each patient's vascular system that continuously accounted for secretion, clearance, hemodilution, blood loss and transfusion. RESULTS AND CONCLUSIONS: At baseline, the average t-PA and PAI-1 secretion rates were 0.74+/-0.33 and 1.28+/-0.74 pmol/s, respectively. Within 5 min of CPB initiation, t-PA secretion increased six-fold to 4.41+/-2.58 pmol/s, while PAI-1 secretion was unchanged, resulting in a six-fold increase in active t-PA levels. t-PA secretion remained elevated throughout CPB and into the early post-operative period. Average PAI-1 secretion did not start to increase until the end of CPB. By 2 h after surgery, average PAI-1 secretion had increased 15-fold to 19.60+/-17.10 pmol/s, resulting in reduced levels of active t-PA even though t-PA secretion was still elevated. We conclude that CPB induces an immediate sustained increase in t-PA secretion followed by a delayed progressive increase in PAI-1 production. Variations in the level of active t-PA are a function of the relative rates of t-PA versus PAI-1 secretion at different times during and after surgery.
INTRODUCTION: Cardiopulmonary bypass (CPB) is associated with elevated tissue plasminogen activator (t-PA) levels during CPB and increased plasminogen activator inhibitor 1 (PAI-1) levels post-operatively. The goal of this study was to estimate the rate of t-PA and PAI-1 secretion in vivo, before, during and after CPB. MATERIALS AND METHODS: Estimated rates of t-PA and PAI-1 secretion were based on measured levels of active and total t-PA, and active and total PAI-1, obtained before, during and after CPB from nine males, combined with a computer model of each patient's vascular system that continuously accounted for secretion, clearance, hemodilution, blood loss and transfusion. RESULTS AND CONCLUSIONS: At baseline, the average t-PA and PAI-1 secretion rates were 0.74+/-0.33 and 1.28+/-0.74 pmol/s, respectively. Within 5 min of CPB initiation, t-PA secretion increased six-fold to 4.41+/-2.58 pmol/s, while PAI-1 secretion was unchanged, resulting in a six-fold increase in active t-PA levels. t-PA secretion remained elevated throughout CPB and into the early post-operative period. Average PAI-1 secretion did not start to increase until the end of CPB. By 2 h after surgery, average PAI-1 secretion had increased 15-fold to 19.60+/-17.10 pmol/s, resulting in reduced levels of active t-PA even though t-PA secretion was still elevated. We conclude that CPB induces an immediate sustained increase in t-PA secretion followed by a delayed progressive increase in PAI-1 production. Variations in the level of active t-PA are a function of the relative rates of t-PA versus PAI-1 secretion at different times during and after surgery.
Authors: Maria Francilene S Souza; Juliano G Penha; Nair Y Maeda; Filomena R B G Galas; Kelly C O Abud; Eloisa S Carvalho; Ana Maria Thomaz; Claudia R P Castro; Juliana Pereira; Antonio Augusto Lopes Journal: Mediators Inflamm Date: 2022-01-15 Impact factor: 4.711