Uptake of &lt;sup&gt;125&lt;/sup&gt;I-Lys-Plasminogen by in vitro Thrombi

Iga, Yoshiro; Greenwald, Sylvia R.; Chandler, Bleakley

doi:10.1159/000214700

Cited by 3 publications

(4 citation statements)

References 21 publications

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“…Furthermore, the thrombus uptake is af fected by the method employed, i.e. incorporation or adsorption, and also by the perfusion time [14].…”

Section: Formation O F L2si-labelled In Vitro Thrombimentioning

confidence: 99%

Kinetics of Urokinase-Induced Thrombolysis in a Biphasic in vitro System

Iga¹,

Stella²,

Chandler³

1985

Pathophysiol Haemos Thromb

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The role and effect of added lys-plasminogen (lys-PLG) on urokinase-induced thrombolysis in an in vitro biphasic system were investigated. The kinetics of lysis of whole blood thrombi was followed in perfusion mediums of normal plasma, PLG-deficient plasma and normal saline using a high and a low concentration of urokinase (UK). The lysis of standard whole blood thrombi in whole blood perfusion mediums to which had been added UK alone or UK plus lys-PLG was compared to whole blood thrombi enriched with lys-PLG by incorporation during thrombus formation or by adsorption during perfusion. In addition, the kinetics of lysis of PLG-deficient fibrin thrombi perfused in PLG-deficient plasma or normal saline was studied when lys-PLG had been added to the thrombus, to the perfusion medium or to both thrombus and medium. In PLG-deficient plasma from which plasmin inhibitors had not been removed, thrombolysis was minimal even at a high concentration of UK. This effect could be neutralized, and to some extent, regulated, by lys-PLG enrichment of the medium. Both PLG-incorporated and PLG-adsorbed whole blood thrombi gave initial and sustained acceleration of UK-induced lysis in comparison with standard nontreated thrombi. It is concluded that in a blood-thrombus biphasic thrombolytic system induced by UK, there is interaction between the phases, and that PLG in both phases influences thrombolysis.

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“…Furthermore, the thrombus uptake is af fected by the method employed, i.e. incorporation or adsorption, and also by the perfusion time [14].…”

Section: Formation O F L2si-labelled In Vitro Thrombimentioning

confidence: 99%

Kinetics of Urokinase-Induced Thrombolysis in a Biphasic in vitro System

Iga¹,

Stella²,

Chandler³

1985

Pathophysiol Haemos Thromb

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“…The molecular weight of ALB was 66,000 daltons. Both were radioiodinated (12SI-PLG, l25I-ALB) by a modification [3] of the chloramine T method of McConahey and Dixon [4],…”

Section: Reagentsmentioning

confidence: 99%

“…After obtaining informed consent, venous blood was drawn from healthy adult male donors into a syringe containing 1 part 3.8% sodium citrate (USP) to 9 parts blood as previously reported [3], Thrombi were made in vitro from recalcified citrated whole blood that flowed in rotating loops of polyethylene tubing at 37 °C [3], The loops were rotated for a total of 30 min to allow completion of thrombus formation by retraction and packing. The in vitro thrombi [5] closely resemble in vivo thrombi and are composed of a platelet-fibrin head with aggregated platelets and a contiguous tail of closely packed strands of fibrin, entrapped red cells and leukocytes, and a small inter stitial fluid compartment.…”

Section: In Vitro Thrombimentioning

confidence: 99%

“…It is known that such large plasma molecules as fibrinogen may permeate a thrombus [1,2]. We have shown by autoradiography that radioiodin ated Lys-plasminogen (125I-PLG) may pene trate into the center o f an in vitro thrombus from the surrounding plasma medium [3]. Whether or not there is constant interchange o f molecular plasma components between the internal milieu o f a thrombus and the external plasma milieu that bathes it is not presently known; however, it would seem reasonable to expect some fluid molecular interchange to occur as in other tissue com partments o f the body.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Exchange between Blood and in vitro Thrombi

Iga

Stella

Chandler

1984

Pathophysiol Haemos Thromb

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Uptake of radioiodinated Lys-plasminogen (¹²⁵I-PLG), albumin (¹²⁵I-ALB), and tritiated water (³H-H₂O) by in vitro thrombi and interchange of these molecules with blood in an in vitro perfusion system were investigated. The radioisotopes were taken up by thrombi either by incorporation during formation in radiolabelled blood or by perfusion of preformed nonradioactive thrombi in radiolabelled blood. Release of the radioisotopes into a perfusion medium of nonradiolabelled blood was then monitored over a 120-min period. The small molecules of ³H-H₂O were rapidly released from the thrombi and achieved equilibrium with the perfusion medium by 120 min in that the specific radioactivity (cpm/mg) of the thrombi equalled that of the medium. The larger molecules of ¹²⁵I-PLG and ¹²⁵I-ALB were more slowly released and did not reach equilibrium with the perfusion medium over the period studied. Release of ¹²⁵I-ALB was intermediate between that of ³H-H₂O and ¹²⁵I-PLG. The greater retention of ¹²⁵I-PLG by the thrombi was consistent with the high binding affinity of plasminogen for fibrin. The demonstrated movement of these radioisotopes between medium and thrombus suggests that thrombi exist in blood in a dynamic state of flux, exhibiting a fluid exchange of molecules between the interstitial compartment of the thrombus and blood.