To elucidate which component(s) of thei fibrinolytic system is (are) responsible for the diurnal variation of fibrinolytic activity we have studied several parameters of this system in 8 healthy male volunteers during a period of. 24 h. Blood was collected at 8 a. m., 10 a. m., 12 a. m., 4 p.m., 8 p.m. and 8 a. m. next morning. The following tests were performed: euglobulin clot lysis time (ECLT), fibrinolytic activity of euglobulins on fibrin plates in the presence and absence of blocking antibodies to tissue-type plasminogen activator (t-PA) and/or urokinase (u-PA), overall plasminogen activator inhibitor (PAI) activity, antigen levels of t-PA, u-PA and PAI-I and zymography of the euglobulin fraction after SDS-PAGE. From 8-10 a. m. to 4-8 p. m., total fibrinolytic activity increased by 1l3% (p <0.01) or 71%h (p <0.01) when measured by ECIX or by fibrin plate assay, respectively. The immunoquenching experiments showed that this increase was entirely due to t-PA related activity whereas u-PA activity and t-PA/u-PA independent activity remained constant during the day. Average antigen levels of u-PA and t-PA in the afternoon were 6% and 25% lower than those measured in the morning. During this period, overall PAI activity and PAI-1 antigen decreased by 3l% (p <0.01) and 52% (p <0.01) respectively. Electrophoretic-zymographic analysis of_ the euglobulins revealed that throughout the day the majority of t-PA was present in the form of the 110 kDa t-PA/PAI-I complex. The intensity of this cornplex was lowest in the afternoon. Free t-PA was almost undetectable in morning samples, but constituted a significant proportion of total t-PA in the afternoon. The diurnal increase of fibrinolytic activity, therefore, is not due to an augmentation of antigen levels of t-PA and/or u-PA but to a decline of those of PAI-1.

SummaryAn impaired fibrinolytic activity after a venous occlusion test is the most common abnormality associated with thomboembolic disease. To better characterize the causes of abnormal responses we have measured different fibrinolytic parameters, before and after 10 and 20 min of venous occlusion, in 77 patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism and in 38 healthy volunteers.The patients had a lower mean fibrinolytic response to venous occlusion than the controls and higher antigen levels of tissue-type plasminogen activator (t-PA: Ag) and plasminogen activator inhibitor type 1 (PAI-1:Ag). Before venous occlusion, PAI-1 levels were at a molar excess over those of t-PA in all patients and controls. After 20 min of venous occlusion, the release of t-PA from the vascular endothelium resulted in a molar excess of t-PA over PAI-1 in the majority of controls (72%) but only in a minority of patients (39%).To identify patients with fibrinolytic abnormalities, reference intervals (RI) for fibrinolytic activity, t-PA:Ag and PAI-1:Ag were established in healthy controls. None of the patients had low levels of t-PA:Ag, but 17 (22%) had elevated PAI-1:Ag levels before venous occlusion and 12 (16%) exhibited low fibrinolytic activity after 20 min of venous occlusion. Ten of these were among the 17 subjects with high PAI-1: Ag levels before venous occlusion. Thus, the measurement of PAI-1:Ag levels before venous occlusion (i.e. in samples taken without any stimulation) is a sensitive (83%) and specific (89%) assay for the detection of patients with an impaired fibrinolytic response to venous occlusion.

The aim of this study was to evaluate the efficacy of tropisetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, versus placebo in the prevention of postoperative nausea and vomiting in patients undergoing general anesthesia for gynecologic surgery. Ten minutes before induction of general anesthesia, 80 patients received in a double-blind manner a single intravenous (IV) injection of either 5 mg tropisetron or a matching placebo. Anesthesia was induced with thiopental and maintained with nitrous oxide and enflurane in oxygen. In the first 24 h postoperatively 7 of 40 patients (17.5%) given tropisetron and 16 of 40 patients (40%) receiving placebo vomited (P < 0.05). The incidence of nausea was 30% (12/40) in the tropisetron group and 52% (21/40) in the placebo group (P < 0.05). A total effective antiemetic response showed 26 patients (65%) in the tropisetron group and 16 patients (40%) in the placebo group (P < 0.05). We conclude that tropisetron given IV prior to gynecologic procedures in general anesthesia significantly reduces postoperative nausea and vomiting when compared to placebo without causing any adverse effect.

No abstract