No Influence of acute hypertriglyceridemia on plasma t-PA in healthy male volunteers.
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 microg/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.
Kemme
M J
MJ
Centre for Human Drug Research, Zernikedreef 10, 2333 CL, Leiden, Netherlands. mk@chdr.nl
Burggraaf
J
J
Schoemaker
R C
RC
Cohen
A F
AF
D000208:Acute Disease; D000328:Adult; D018592:Cross-Over Studies; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D008102:Liver Circulation; D008297:Male; D008657:Metabolic Clearance Rate; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D012039:Regional Blood Flow; D010959:Tissue Plasminogen Activator / Q000097:blood* / Q000187:drug effects / Q000493:pharmacokinetics
D005217:Fat Emulsions, Intravenous; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator