No Influence of Acute Hypertriglyceridemia on Plasma t-PA in Healthy Male Volunteers

Abstract

Dietary effects on liver blood flow may have biased the previously observed effects of hypertriglyceridemia on systemic tissue-type plasminogen activator (t-PA) concentrations. Therefore, in this study the effects of hypertriglyceridemia on plasma t-PA were determined by inducing hypertriglyceridemia with an intravenous fat emulsion (Intralipid) infusion. In a randomised crossover fashion, eight healthy male volunteers received Intralipid 10% (1.5 ml/min) or 0.9% saline for 2 h and 45 min. After 2 h of infusion, t-PA antigen, t-PA activity, t-PA/plasminogen activator inhibitor (PAI-1) complex, and PAI-1 activity were determined. Concomitantly, the effects of Intralipid t-PA clearance were determined from steady-state t-PA antigen concentrations of a 45-min recombinant tissue-type plasminogen activator (rt-PA) infusion (31.25 μg/min). Liver blood flow was assessed from steady-state concentrations of a continuous sorbitol infusion. Differences between treatments were calculated using the prevalue as the covariate. No significant differences were observed in mean±S.D. endogenous concentrations of t-PA antigen, 4.5±0.9/4.1±0.9 ng/ml (Intralipid vs. saline infusion; difference of 0.3 ng/ml, 95% confidence interval, CI: −0.2, 0.8); t-PA activity, 0.69±0.21/0.68±0.21 U/ml (difference of 0.04 U/ml, CI: −0.17, 0.25); t-PA/PAI-1 complex, 2.0±1.3/1.6±1.0 ng/ml (difference of 0.1 ng/ml, CI: −0.8, 0.6); and PAI-1 activity, 7.3±5.1/7.1±5.1 U/ml (difference of 0.26 U/ml, CI: −3.7, 4.3). Mean t-PA clearance and liver blood flow were unaffected by the Intralipid infusion. These results indicate that acute hypertriglyceridemia does not alter plasma fibrinolytic parameters in healthy male volunteers.