Effects of flow on recombinant tissue plasminogen activator-induced pulmonary thrombolysis

1991 ◽  
Vol 71 (4) ◽  
pp. 1441-1446 ◽  
Author(s):  
R. M. Prewitt ◽  
S. A. Gu ◽  
D. Greenberg ◽  
S. M. Chan ◽  
U. Schick ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Recombinant Tissue Plasminogen Activator ◽  
Canine Model ◽  
Mean Pulmonary Arterial Pressure ◽  
Tissue Plasminogen ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

We employed a canine model of pulmonary embolism induced by injection of radioactive blood clots to investigate effects of changes in cardiac output (CO) on recombinant tissue plasminogen activator- (rtPA) induced pulmonary thrombolysis. Rate and extent of thrombolysis were assessed with a gamma camera. Eighteen dogs were studied. Emboli increased mean pulmonary arterial pressure and decreased CO from 2.6 to 1.9 l/min (P less than 0.001). Subsequently, dogs were randomly divided into three groups: group 1 received 0.5 mg/kg of rtPA over 30 min; 30 min before the same dose regimen of rtPA, in the six group 2 dogs, mean CO was increased to approximately 3.25 l/min by opening one systemic arteriovenous fistula; in the six group 3 dogs, before rtPA, mean CO was increased to approximately 4.5 l/min by opening two or three fistulas. After embolization, CO remained low in group 1; the mean 2-h time-averaged CO was 1.8 l/min. CO was much higher in groups 2 and 3 (3.3 and 4.6 l/min, respectively; both P less than 0.001 compared with group 1; and P less than 0.001, group 2 vs. group 3). Compared with group 1, corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in flow per se augments rtPA-induced pulmonary thrombolysis. Also, because thrombolysis was similar between groups 2 and 3, these results define an upper limit to the flow-thrombolytic relationship with rtPA.

Recombinant tissue plasminogen activator treatment of pulmonary embolism also improves deep venous thrombosis

2018 ◽  
Vol 66 (7) ◽  
pp. 1045-1049
Author(s):  
Mukremin Er
Keyword(s):  
Pulmonary Embolism ◽  
Thrombolytic Therapy ◽  
Venous Thrombosis ◽  
Plasminogen Activator ◽  
Enoxaparin Sodium ◽  
Anticoagulation Therapy ◽  
Recombinant Tissue Plasminogen Activator ◽  
Tissue Plasminogen ◽  
Group 2 ◽  
Group 1

Anticoagulants are the standard form of treatment used in deep vein thrombosis (DVT). Thrombolytic therapy is another method to treat thromboembolism by using intravenous administration of streptokinase, urokinase and recombinant tissue plasminogen activator (r-tPA). We have investigated the effect of r-tPA, a systemic thrombolytic used for the treatment of pulmonary emboli, on DVT in the same patients. 130 patients who were diagnosed with both pulmonary embolism and DVT were included in this study. Lower extremity Doppler ultrasonography (DUS) was conducted on all of the patients upon admission and then on the 6th month. The patients were divided into two groups. Patıents in Group 1 were initially given 100 mg thrombolytic (r-tPA) intravenously and then standard anticoagulation therapy (enoxaparin sodium and warfarin). Patients in Group 2, however, were given only standard anticoagulation therapy (enoxaparin sodium and warfarin). In the 6th month DUS follow-up control for Group 1, out of 66 cases, the venous thrombosis of 54 patients were completely resolved, and the remaining 12 patients had residual vein occlusion (RVO). In Group 2, out of 64 cases, 41 patients were found to have complete resolution, while 23 patients continued to have RVO. This difference was statistically significant (p=0.029). OR was calculated to be 2.47. In other words, the risk of RVO was increased by 2.47 times in the patients who were not treated with r-tPA. Thrombolytic therapy of DVT should be considered more frequently to avoid complications of thrombosis, and DUS monitoring should be recommended before discontinuing anticoagulant therapy.

Investigation by HPLC of the Catabolism of Recombinant Tissue Plasminogen Activator in the Rat

1988 ◽  
Vol 60 (01) ◽  
pp. 107-112 ◽  
Author(s):  
Roy Harris ◽  
Louis Garcia Frade ◽  
Lesley J Creighton ◽  
Paul S Gascoine ◽  
Maher M Alexandroni ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Half Life ◽  
Recombinant Tissue Plasminogen Activator ◽  
Rat Plasma ◽  
High Molecular Weight Complex ◽  
Molecular Weights ◽  
Major Activity ◽  
Tissue Plasminogen

SummaryThe catabolism of recombinant tissue plasminogen activator (rt-PA) was investigated after injection of radiolabelled material into rats. Both Iodogen and Chloramine T iodination procedures yielded similar biological activity loss in the resultant labelled rt-PA and had half lives in the rat circulation of 1 and 3 min respectively. Complex formation of rt-PA was investigated by HPLC gel exclusion (TSK G3000 SW) fractionation of rat plasma samples taken 1-2 min after 125I-rt-PA injection. A series of radiolabelled complexes of varying molecular weights were found. However, 60% of the counts were associated with a single large molecular weight complex (350–500 kDa) which was undetectable by immunologically based assays (ELISA and BIA) and showed only low activity with a functional promoter-type t-PA assay. Two major activity peaks in the HPLC fractions were associated with Tree t-PA and a complex having a molecular weight of ̴ 180 kDa. HPLC fractionation to produce these three peaks at various timed intervals after injection of 125I-rt-PA showed each to have a similar initial rate half life in the rat circulation of 4-5 min. The function of these complexes as yet is unclear but since a high proportion of rt-PA is associated with a high molecular weight complex with a short half life in the rat, we suggest that the formation of this complex may be a mechanism by which t-PA activity is initially regulated and finally cleared from the rat circulation.

Bioavailability in Rats of Human Recombinant Tissue Plasminogen Activator After Subcutaneous and Intramuscular Injection

1986 ◽  
Vol 56 (03) ◽  
pp. 299-301 ◽  
Author(s):  
L J Garcia Frade ◽  
S Poole ◽  
S Hanley ◽  
L J Creighton ◽  
A D Curtis ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Inferior Vena ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Vena Cava ◽  
Recombinant Tissue Plasminogen Activator ◽  
Fibrin Plate ◽  
Tissue Plasminogen

SummaryThe bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection.

Association of admission leukocyte count with clinical outcomes in acute ischemic stroke patients undergoing intravenous thrombolysis with recombinant tissue plasminogen activator

2020 ◽  
Vol 17 ◽  
Author(s):  
Jie Chen ◽  
Fu-Liang Zhang ◽  
Shan Lv ◽  
Hang Jin ◽  
Yun Luo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Leukocyte Count ◽  
Intravenous Thrombolysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Functional Independence ◽  
Tissue Plasminogen ◽  
Poor Outcomes

Objective:: Increased leukocyte count are positively associated with poor outcomes and all-cause mortality in coronary heart disease, cancer, and ischemic stroke. The role of leukocyte count in acute ischemic stroke (AIS) remains important. We aimed to investigate the association between admission leukocyte count before thrombolysis with recombinant tissue plasminogen activator (rt-PA) and 3-month outcomes in AIS patients. Methods:: This retrospective study included consecutive AIS patients who received intravenous (IV) rt-PA within 4.5 h of symptom onset between January 2016 and December 2018. We assessed outcomes including short-term hemorrhagic transformation (HT), 3-month mortality, and functional independence (modified Rankin Scale [mRS] score of 0–2 or 0–1). Results:: Among 579 patients who received IV rt-PA, 77 (13.3%) exhibited HT at 24 h, 43 (7.4%) died within 3 months, and 211 (36.4%) exhibited functional independence (mRS score: 0–2). Multivariable logistic regression revealed admission leukocyte count as an independent predictor of good and excellent outcomes at 3 months. Each 1-point increase in admission leukocyte count increased the odds of poor outcomes at 3 months by 7.6% (mRS score: 3–6, odds ratio (OR): 1.076, 95% confidence interval (CI): 1.003–1.154, p=0.041) and 7.8% (mRS score: 2–6, OR: 1.078, 95% CI: 1.006–1.154, p=0.033). Multivariable regression analysis revealed no association between HT and 3-month mortality. Admission neutrophil and lymphocyte count were not associated with 3-month functional outcomes or 3-month mortality. Conclusion:: Lower admission leukocyte count independently predicts good and excellent outcomes at 3 months in AIS patients undergoing rt-PA treatment.

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