Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC).
The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism o...
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doaj-4bf75081ab6c4160bd92fb2d8b3bb8c42021-08-23T12:22:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01162e024749610.1371/journal.pone.0247496Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC).Dongjune KimSusan M SheaDavid N KuThe search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi. We have developed an in vitro system to study the efficacy of known and proposed thrombolytic agents on white clots formed from whole blood in a stenosis with arterial conditions. The agents and adjuncts tested were tPA, ADAMTS-13, abciximab, N-acetyl cysteine, and N,N'-Diacetyl-L-cystine (DiNAC). Most of the agents, including tPA, had little thrombolytic effect on the white clots. In contrast, perfusion of DiNAC lysed thrombi as quickly as 1.5 min, which ranged up to 30 min at lower concentrations, and resulted in an average reduction in surface area of 71 ± 20%. The clot burden was significantly reduced compared to both tPA and a saline control (p<0.0001). We also tested the efficacy of all agents on red fibrinous clots formed in stagnant conditions. DiNAC did not lyse red clots, whereas tPA significantly lysed red clot over 48 h (p<0.01). These results lead to a novel use for DiNAC as a possible thrombolytic agent against acute arterial occlusions that could mitigate the risk of hyper-fibrinolytic bleeding.https://doi.org/10.1371/journal.pone.0247496 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dongjune Kim Susan M Shea David N Ku |
spellingShingle |
Dongjune Kim Susan M Shea David N Ku Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC). PLoS ONE |
author_facet |
Dongjune Kim Susan M Shea David N Ku |
author_sort |
Dongjune Kim |
title |
Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC). |
title_short |
Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC). |
title_full |
Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC). |
title_fullStr |
Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC). |
title_full_unstemmed |
Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC). |
title_sort |
lysis of arterial thrombi by perfusion of n,n'-diacetyl-l-cystine (dinac). |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2021-01-01 |
description |
The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi. We have developed an in vitro system to study the efficacy of known and proposed thrombolytic agents on white clots formed from whole blood in a stenosis with arterial conditions. The agents and adjuncts tested were tPA, ADAMTS-13, abciximab, N-acetyl cysteine, and N,N'-Diacetyl-L-cystine (DiNAC). Most of the agents, including tPA, had little thrombolytic effect on the white clots. In contrast, perfusion of DiNAC lysed thrombi as quickly as 1.5 min, which ranged up to 30 min at lower concentrations, and resulted in an average reduction in surface area of 71 ± 20%. The clot burden was significantly reduced compared to both tPA and a saline control (p<0.0001). We also tested the efficacy of all agents on red fibrinous clots formed in stagnant conditions. DiNAC did not lyse red clots, whereas tPA significantly lysed red clot over 48 h (p<0.01). These results lead to a novel use for DiNAC as a possible thrombolytic agent against acute arterial occlusions that could mitigate the risk of hyper-fibrinolytic bleeding. |
url |
https://doi.org/10.1371/journal.pone.0247496 |
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