Counteraction of Platelet Activity at Sites of Laser-induced Endothelial Trauma

Ke, Arfors; Hc, Hint; Dp, Dhall; Na, Matheson

doi:10.1136/bmj.4.5628.430

Cited by 62 publications

(21 citation statements)

References 6 publications

(9 reference statements)

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“…This find ing is in accordance with results reported by several other investigators [2,7,10,12,13,15] while some authors reported negative re sults [16,[18][19][20], These controversial find ings may be explained by the different exper imental models used and also by the different ways to interpret the results. So, if thrombus formation is evaluated during the first min utes after the vascular lesions, dipyridamole is usually markedly effective [2,7,10,12,13,15], while in models in which the thrombi are evaluated a longer time after their origin (usually hours) ASA has been found to be more effective than dipyridamole [16,[18][19][20], 10 mg dipyridamole/kg were less effec tive if administered intravenously. Here the antithrombotic effect was tested 30 min after injection compared to 90-120 min after oral application.…”

Section: Discussionsupporting

confidence: 80%

Laser-Induced Thrombi in Rat Mesenteric Vessels and Antithrombotic Drugs

Weichert¹,

Pauliks²,

Breddin³

1983

Pathophysiol Haemos Thromb

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A method to induce microthrombi in small mesenteric arteries (ø 15–25 μm) has been developed to study platelet reactions and to investigate antithrombotic drugs. A high power water immersion interference contrast system, based on a Leitz Orthoplan microscope, was used. In Nembutal-anesthetized male Wistar rats and in fawn hooded bleeder rats, vascular lesions were produced with a Hadron-512-Ruby-bio-laser or with a Coherent CR-2 supergraphite ion laser (Argon laser). The ruby laser produced intravascular precipitates consisting of proteins and erythrocytes which usually stuck to the vessel wall and on which platelets immediately adhered, transformed with pseudopode formation and formed loose aggregates. The Argon laser induced vascular damage, usually without intravascular heat precipitates which also led to platelet adhesion, transformation and aggregation. Fibrin threads rarely formed in the early platelet thrombi. Thrombus formation was significantly reduced in this model by dipyridamole (10 mg/kg orally), by Ditazole (50 mg/kg orally), heparin (100 IU/kg i.v.), Molsidomine (50 mg/kg orally), Nafazatrom (Bay G 6575, 10 mg/kg i.v. and orally), Ticlopidine (100 and 200 mg/kg orally) and Tioxaprofen (EMD 26644, 10 mg/kg orally). Thrombus formation was also significantly reduced in fawn hooded bleeder rats.

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Section: Discussionsupporting

confidence: 80%

Laser-Induced Thrombi in Rat Mesenteric Vessels and Antithrombotic Drugs

Weichert¹,

Pauliks²,

Breddin³

1983

Pathophysiol Haemos Thromb

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“…Our findings that SCIP conversion leads to down-regulation of platelet surface adhesiveness may provide a partial explanation for previous observations that platelets in direct contact with exposed subendothelium eventually become non-reactive toward other platelets (40,45,46). Given the central role played by integrin ␣ IIb b 3 in hemostasis and thrombogenesis, unraveling the molecular mechanisms utilized by FXIII and calpain to regulate integrin ␣ IIb b 3 receptor function may have pathophysiological importance.…”

Section: Discussionsupporting

confidence: 46%

Platelet Factor XIII and Calpain Negatively Regulate Integrin αIIbβ3 Adhesive Function and Thrombus Growth

Kulkarni

Jackson

2004

Journal of Biological Chemistry

142

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Excessive accumulation of platelets at sites of atherosclerotic plaque rupture leads to the development of arterial thrombi, precipitating clinical events such as the acute coronary syndromes and ischemic stroke. The major platelet adhesion receptor glycoprotein (GP) IIbIIIa (integrin ␣ IIb ␤ 3 ) plays a central role in this process by promoting platelet aggregation and thrombus formation. We demonstrate here a novel mechanism downregulating integrin ␣ IIb ␤ 3 adhesive function, involving platelet factor XIII (FXIII) and calpain, which serves to limit platelet aggregate formation and thrombus growth. This mechanism principally occurs in collagenadherent platelets and is induced by prolonged elevations in cytosolic calcium, leading to dramatic changes in platelet morphology (membrane contraction, fragmentation, and microvesiculation) and a specific reduction in integrin ␣ IIb ␤ 3 adhesive function. Adhesion receptor signal transduction plays a major role in the process by sustaining cytosolic calcium flux necessary for calpain and FXIII activation. Analysis of thrombus formation on a type I fibrillar collagen substrate revealed an important role for FXIII and calpain in limiting platelet recruitment into developing aggregates, thereby leading to reduced thrombus formation. These studies define a previously unidentified role for platelet FXIII and calpain in regulating integrin ␣ IIb ␤ 3 adhesive function. Moreover, they demonstrate the existence of an autoregulatory feedback mechanism that serves to limit excessive platelet accumulation on highly reactive thrombogenic surfaces.

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“…This was expected since the major effect of heparin is on clotting factors (i.e., anticoagulation) rather than on platelet aggregation per se. In fact, Arfors et al, 18 Honour and Mitchell, 2 and Born and Philp 3 also failed to demonstrate an effect of heparin on either laser-induced or mechanically induced aggregates in rabbit ear chambers or rabbit pial vessels.…”

Section: Effects Of Other Drugs and Localization Of Drug Effectmentioning

confidence: 97%

Platelet aggregation in the cerebral microcirculation: effect of aspirin and other agents.

Rosenblum¹,

El‐Sabban²

1977

Circulation Research

153

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After a certain period of time filtered ultraviolet light produces platelet aggregation in microvessels on the cerebral surface of the mouse, but only when sodium fluorescein is first injected intravascularly to provide a light-absorbing, heat-generating target. The platelet aggregates fluoresce. They occur only in the illuminated field and adhere to arteriolar and venular walls. Vasoconstriction is not detected prior to or up to 30 seconds after aggregation. Electron microscopy reveals damaged endothelium and undamaged red cells, as well as aggregates consisting almost exclusively of platelets in varying stages of aggregation, pseudopod formation, and degranulation. The time between onset of the noxious stimulus and recognition of the first aggregate can be measured as the vessels are observed microscopically. This "time of aggregation" is prolonged by pentobarbital as opposed to urethane anesthesia, and also is related to time elapsed after craniotomy. We also found that aspirin and indomethacin significantly prolong time to first aggregate, but only on the arteriolar side of the circulation. This is so even though the composition of the aggregates is the same on both the arteriolar and venular sides. Heparin has no effect.

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Counteraction of Platelet Activity at Sites of Laser-induced Endothelial Trauma

Cited by 62 publications

References 6 publications

Laser-Induced Thrombi in Rat Mesenteric Vessels and Antithrombotic Drugs

Laser-Induced Thrombi in Rat Mesenteric Vessels and Antithrombotic Drugs

Platelet Factor XIII and Calpain Negatively Regulate Integrin αIIbβ3 Adhesive Function and Thrombus Growth

Platelet aggregation in the cerebral microcirculation: effect of aspirin and other agents.

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