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ID naloge: 91 Letnik: 2000 Predmet: patofiziologija
Vpliv tangencialnega toka plazme na raztapljanje
krvnih strdkov
Avtor: Mitja Štrukelj, dr. med
Mentor: doc. dr. Aleš Blinc, dr. med.
Raztapljanje trombov, ki popolnoma zapirajo žilo, sprva poteka v obliki kanalov, ki delno rekanalizirajo žilo, skoraj nikoli pa se strdek ne raztopi v celoti že v zacetni fazi. Ko se ustvari prvi reperfuzijski kanal skozi celotno dolžino strdka, skozenj stece hiter tok krvi, raztapljanje pa poteka od roba reperfuzijskega kanala navznoter. Doslej ni bilo znano, ali ob hitrem toku plazme skozi kanal v strdku zunanja plazma, ki vsebuje s tromboliticino sredstvo, vstopa v strdke le z difuzijo ali tudi s hitrejšim konvekcijskim tokom, ki ga povzroca turbulenten tok v reperfuzijskem kanalu. Z raziskavo smo želeli na modelnem sistemu in vitro preveriti, kako so se raztapljali neokluzivni krvni strdki in modelni strdki iz ocišcenega fibrinogena, ki smo jim primešali eritrocite ob hitrem tangencialnem toku plazme. Plazmi smo dodali fibrinsko specificni tkivni aktivator plazminogena (t-PA) v koncentraciji 2 mg/ml, ali fibrinsko nespecificno tromboliticno zdravilo streptokinazo v koncentraciji 250 E/ml. Takšni koncentraciji tromboliticnih sredstev smo izbrali, ker sta bili enaki povprecni plazemski koncentraciji med tromboliticnim zdravljenjem srcnega infarkta. Valjaste strdke s premerom 3 mm in dolžino 3 cm smo vzdožno preluknjali z iglo premera 0.7 mm in jih vpeli v perfuzijski sistem , skozi katerega smo poganjali tok plazme z zacetno hitrostjo 426 ± 13 cm/s in koncno hitrostjo 86 ± 3 cm/s ob popolni raztopitvi strdka. Na precnem preseku skozi sredino strdkov smo s slikanjem z magnetno resonanco opazovali prodiranje plazme, oznacene s kontrastnim sredstvom Gd-DTPA, iz kanala v notranjost strdka. Istocasno smo merili tudi raztapljanje strdkov. Prodiranje oznacene plazme v strdke ni bilo odvsino od izbire tromboliticnega sredstva. Po 6 min smo izmerili prisotnost Gd-DTPA na razdalji 1.78 ± 0.49 mm od roba kanala pri strdkih, ki smo jih raztaplajli s streptokinazo, in na razdalji 2.22 ± 0.25 mm pri strdkih, ki smo jih raztapljali s t-PA (p = 0.11). Raztapljanje strdkov je bilo znacilno hitrejše, kadar smo uporabili fibrinsko specificni aktivator plazminogena t-PA, kot kadar smo uporabili streptokinazo. Že po 12 minutah raztapljanja se je precni presek krvnih strdkov, izpostavljenih t-PA, zmanjšal na 0.42 ± 0.26 zacetne velikosti. Ob enakem casu je znašala relativna velikost preseka skozi krvne strdke, izpostavljene streptokinazi, 0.73 ± 0.20 zacetne velikosti ( p < 0.029). Razlike so bile od 12. minute dalje znacilne do konca opazovanja pri 40 min. Koncentracija plazminogena se v plazmi, ki smo ji dodali t-PA, ni pomembno spremenila. V plazmi, ki smo ji dodali streptokinazo, pa se je koncentracija plazminogena po eni uri zmanjšala na približno tretjino zacetne vrednosti. Zakljucili smo, da hiter, turbulenten tok plazme ob krvnem strdku povzroci vstopanje zunanje plazme v strdke, ki je mnogo hitrejše, kot bi ga lahko pricakovali zgolj s pasivno difuzijo. Ob prodiranju zunanje plazme v strdke se le-ti raztapljajo pomembno hitreje, kadar plazma vsebuje fibrinsko specificni aktivator plazminogena t-PA in ni osiromašena s plazminogenom, kakor pa tedaj, ko je plazma osiromašena s plazminogenom ob uporabi fibrinsko-nespecificnega aktivatorja plazminogena, streptokinaze.
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[Abstract / English version]
Vpliv tangencialnega toka plazme na raztapljanje
krvnih strdkov
Author: Mitja Štrukelj, dr. med
Mentor: doc. dr. Aleš Blinc, dr. med.
Lysis of occlusive thrombi initially proceeds via penetrating channels that reacanalize the occluded vessel, but does not result in complete dissolution of the clot. When the first reperfusion channel pierces the clot, blood starts flowing through the channel and further blood clot lysis proceeds from the borders of the channel into the direction of the remaining clot. It has not been known whether tangential flow of blood plasma along the clot causes exchange of the serum inside the clot by diffusion alone or also by convective exchange when the tangential flow is turbulent. Our aim was to test on an in vitro model system how non-occlusive whole blood clots and model fibrin clots were dissolved by tangential flow of plasma, that contained either fibrin-specific tissue plasminogen activator (t-PA) at 2 mg/ml, or fibrin non-specific streptokinase at 250 IU/ml. The respective concentrations of t-PA and streptokinase were chosen to represent the average therapeutic concentrations during thrombolytic treatment of myocardial infarction. Cylindrical clots with a diameter of 3 mm and length of 3 cm were formed in glass tubes and pierced lengthwise by a needle with a diameter of 0.7 mm. The nonocclusive clots were connected to a perfusion system. The velocity of plasma flowing through the preformed channel in the clot was initially 426 ± 13 cm/s and fell to 86 ± 3 cm/s after complete clot dissolution. Magnetic resonance imaging of transverse clot sections was used for measuring the transport of plasma, containing the contrast agent Gd-DTPA, from the flow channel into the clot. Simultaneously, clot dissolution was measured. Penetration of contrast agent-containing plasma into clots did not depend on the choice of thrombolytic agent. At 6 min Gd-DTPA-containing areas were found at a distance 1.78 ± 0.49 mm from the border of the channel in clots dissolved with streptokinase, and at a distance of 2.22 ± 0.25 mm in clots dissolved with t-PA (p = 0.11). However, dissolution of blood clots was significantly faster when t-PA was in comparison with streptokinase. After 12 min of clot lysis the cross section of clots, exposed to t-PA was reduced to 0.42 ± 0.26 of their initial size, whereas clots exposed to streptokinase were reduced to only 0.73 ± 0.20 of their initial size (p < 0.029). The differences in clot size remained significant through 40 min. The concentration of plasminogen did not change substantially in plasma containing t-PA, but was reduced to about one third of its initial value when streptokinase was used. We concluded that rapid, turbulent flow of plasma through a channel in the clot caused rapid exchange of the serum inside the clot with outer plasma. The rate of plasma-serum exchange was much more rapid than transport caused by diffusion alone. Using fibrin-specific t-PA that did not deplete the plasma of its plasminogen favourably affected the rate of blood clot lysis in comparison with non fibrin-specific streptokinase that depleted the plasma of two thirds of its plasminogen content.
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