Biolaser Endothelial Trauma as a Means of Quantifying Platelet Activity in vivo

Arfors, Karl-E.; Dhall, D.P.; Engeset, J; Hint, H; Matheson, N. A.; Tangen, O.

doi:10.1038/218887a0

Cited by 62 publications

(20 citation statements)

References 2 publications

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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: 47%

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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Section: Discussionsupporting

confidence: 47%

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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“…Arfors et al [1] proposed varying the laser energy and using the varying energy input, necessary to induce a thrombus in nontreated animals, as a measure of the effect of antithrombotic drugs. In our models the counting of laser lesions with constant energy input, necessary to induce a thrombus in ves sels of similar diameter, proved to be a sim ple and efficient mode to evaluate inhibition of thrombus formation.…”

Section: Discussionmentioning

confidence: 99%

“…The Ruby impulse laser produced an in travascular heat precipitate, consisting of plasma proteins, often some heat-damaged erythrocytes and rarely platelets [1,14], of about 5 pm diameter which usually stuck to the vessel wall. This precipitate was a strong stimulus for platelet adhesion and further platelet aggregation.…”

Section: Discussionmentioning

confidence: 99%

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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“…The authors concluded that there was no direct correlation between the plasma anti-factor Xa levels and the anti thrombotic effect and that other properties of LMWH may contribute to their anti thrombotic action. It was discussed that the primary effect of UFH on intravascular thrombosis may be related to changes in ves-sel wall metabolism rather than in prolonga tion of the clotting time or the inhibition of factor Xa [29], Laser-induced thrombi have been fre quently produced in rat mesenteric vessels to investigate the effect of antithrombotic drugs [7,[30][31][32][33][34], In our model only the first steps of thrombus formation -adhesion and reversible aggregation -can be observed; fibrin strands are rarely seen [6,7], The observed effects of LMWH and UFH might be caused by the inhibition of early phases of coagulation at the endothelial and/or platelet surface. But also the adsorbance of these drugs to endothelial membranes and a re sulting inhibition of platelet adhesion could be responsible for the effect of unfraction ated heparin and LMWH on thrombus for mation in this animal model [13],…”

Section: Discussionmentioning

confidence: 99%

Effect of Low-Molecular-Weight Heparins on Laser-Induced Thrombus Formation in Rat Mesenteric Vessels

Weichert

Breddin²

1988

Pathophysiol Haemos Thromb

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Laser-induced thrombi have been frequently produced in rat mesenteric vessels to investigate the effect of antithrombotic drugs. We have tested low molecular heparins in comparison to unfractionated heparin. The investigations were carried out on male Wistar rats weighing 200–300 g; the animals were anesthetized with pentobarbital sodium (Nembu-tal®) 60 mg/kg i.p. Vascular lesions were induced with a Coherent CR-2 supergraphite ion laser (argon laser) mounted on a Leitz Orthoplan microscope. An intestinal loop was spread on a self-constructed object stage, mounted on the microscope table. The laser beam was directed through the optical path of the microscope on small mesenteric vessels in the fat-free portion of the mesentery. For the evaluation of thrombus formation the number of laser injuries needed to induce a defined thrombus was used. All low-molecular-weight heparins (preparation B, Braun; BR-Z-0601, Braun; CY 216, Choay; Fragmin, Kabi; low molecular heparin, Sandoz and Org 10172, Organon) or unfractionated heparin (Liquemin®; Hoffmann-La Roche) showed a significant and dose-dependent antithrombotic effect after subcutaneous injection, if venules had been damaged. The effect lasted for 48 h, partly for over 48 h. If thrombus formation was studied after intravenous injection into arterioles as well as into venules 8 h after injection, no antithrombotic effect could be demonstrated under the influence of CY 216 or unfractionated heparin.

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Biolaser Endothelial Trauma as a Means of Quantifying Platelet Activity in vivo

Cited by 62 publications

References 2 publications

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

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

Laser-Induced Thrombi in Rat Mesenteric Vessels and Antithrombotic Drugs

Effect of Low-Molecular-Weight Heparins on Laser-Induced Thrombus Formation in Rat Mesenteric Vessels

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