Turnover and fate of fibrinogen and platelets at the rabbit aorta wall immediately after a balloon de-endothelializing injury in vivo

2006 ◽  
Vol 96 (07) ◽  
pp. 60-67 ◽  
Author(s):  
Bonnie Ross ◽  
Marnie Timleck ◽  
Suzanne Southward ◽  
Mary Richardson ◽  
Mark Hatton
Keyword(s):  
Tissue Factor ◽  
Small Proportion ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Arterial Injury ◽  
Artery Wall ◽  
Platelet Releasate ◽  
Hemostasis Factors ◽  
Balloon Catheter Injury

SummaryA de-endothelializing injury to the artery wall in vivo results in a rapid procoagulant response at the surface of the exposed subendothelium. Activated tissue factor (TF)-bearing cells and hemostasis factors located at the site of injury respond by producing thrombin, and within minutes the principal thrombus-forming, blood-borne components (platelets, fibrinogen) accumulate at the site.To compare their behaviors, the rates of uptake and turnover of rabbit 51Cr-platelets and rabbit 125I-fibrinogen were quantified simultaneously during the initial 100-min interval after a balloon catheter injury to the rabbit aorta in vivo.Platelets (∼70,000/mm2) and fibrin(ogen) (∼2.8 pmol/cm2) saturated the ballooned aorta surface within five minutes after injury.Whereas the adherent platelet and fibrinogen concentrations remained steady at the aorta surface, fibrin(ogen)-related products continued to accumulate slowly in the tunica media (TM) for at least 100 minutes. A relatively small proportion (3.7%/min) of adhered platelets turned over at the ballooned aorta surface at 10 minutes, decreasing to 1.2%/min at 100 minutes. By contrast, a larger proportion of fibrin(ogen) (∼ 20%/min) was turned over within the platelet layer at 10 minutes, decreasing to 6%/min at 100 minutes. As verified by immunostaining aorta sections and by protein analysis ofTM extracts,the uptakes of platelets and fibrinogen at the site of injury contributed to an accumulation of products of platelet releasate and fibrin(ogen) degradation (FDPs) within the TM.These observations improve our understanding of the hemostatic processes and subsequent events that occur after an arterial injury in vivo.

THE BEHAVIOUR OF RABBIT PLASMINOGEN AT THE LUMINAL SURFACE OF RABBIT AORTA IN VIVO BEFORE AND AFTER BALLOON-CATHETER INJURY

1987 ◽  
Author(s):  
Mark W C Hatton ◽  
Susan Moar ◽  
Mary Richardson
Keyword(s):  
White Male ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Ruthenium Red ◽  
Transmission Electron ◽  
Before And After ◽  
Ruthenium Red Staining ◽  
Balloon Catheter Injury

A previous study from this laboratory has identified the susceptibility of the de-endothelialised aorta, particularly the proteoglycan (PG) components of the extracellular matrix (ECM), to proteolytic damage if exposed to plasmin in vitro. To explore the possiblity that this occurs in vivo, a possible association between 125I-plasminogen (PLG) binding to the arterial wall, its activation to plasmin (PLN) and, subsequently, proteolytic damage to the intimal ECM has been studied. Intravenous injection of 125I-PLG in healthy N.Z. white male rabbits showed that PLG associated minimally (<0.01% of circulating PLG/cm2 /ml blood at 1 h) with the thoracic aorta endothelium, measured after Hautchen preparation from 1-cm vessel segments. Trans endothelial passage, measured as 125I-PLG associated with thg subendothelium (intima-media), progressed to 0.015%/cm2 /ml blood at 1 h. In contrast, the process of de-endothelialisation by balloon catheter led to a rapid uptake of bI-PLG by the denuded vessel surface. At saturation (approx. 10 min after injury), 0.7 - 0.8% of circulating PLG/cm2/ml blood was adsorbed by the entire de-endothelialised intima-media: Of the adsorbed PLG, 2-3% was associated with the platelet layer. Uptake was not inhibited by eACA (dose: 200 mg/kg) given i.v. before I-PLG. Adsorbed PLG was not released significantly from segments incubated in MEM containing 4% (w/v) RSA in vitro PLN activity was not detected. Furthermore, assessment of the ECM by transmission electron microscopy, after ruthenium red staining, showed that uptake of PLG by the de-endothelialised vessel in vivo was not associated with obvious damage to the PG components. Supported by the Heart and Stroke Foundation of Ontario.

Quantitation of Platelet Adherence to Rabbit Aortae and Platelet Survival After two Injuries with a Balloon Catheter

1979 ◽  
Author(s):  
R.L. Kinlough-Rathbone ◽  
H.M. Groves ◽  
S. Maric ◽  
M.A. Packham ◽  
J.F. Mustard
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Platelet Adherence ◽  
Platelet Survival ◽  
Single Balloon

Following a single balloon catheter injury to a rabbit aorta (INJ 1) a monolayer of platelets covers the subendothelium within 10 min, the surface becomes relatively non-reactive to further platelet accumulation and platelet survival is not altered. We have now studied whether a second similar injury (INJ 2) of the non-reactive, smooth muscle cell-rich neointima 7 days after INJ 1 makes the surface of the neointima reactive to platelets or alters platelet survival. 51Cr-platelet adherence to the neointima of aortae subjected to INJ 2 in vitro 7 days after an initial in vivo injury was not significantly different from the adherence following a single in vitro injury (16,600 ± 3100 platelets/mm2 and 27,600 ± 4000 respectively, ρ > 0.2). In vivo adherence of 51Cr-platelets to the surface of rabbit aortae was similar following INJ 1 (0.084 ± 0.009% of the circulate, platelets) and INJ 2 (0.130 ± 0.03%, p > 0.2). Platelet survival after injury to the neointima was not significantly different in animals with an undamaged aortic endothelium (74.6 ± 5.9 hr and 80.2 ± 4.3 hr respectively, ρ > 0.5). Thus, a second injury involving the smooth’ muscle cell-rich neointima that forms after removal of the endothelium with a balloon catheter does not cause more platelets to accumulate than the initial injury, nor shorten platelet survival.

scholarly journals On the interaction of rabbit antithrombin III with the luminal surface of the normal and deendothelialized rabbit thoracic aorta in vitro

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 878-886
Author(s):  
MW Hatton ◽  
SL Moar ◽  
M Richardson
Keyword(s):  
Thoracic Aorta ◽  
Antithrombin Iii ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Luminal Surface ◽  
High Affinity ◽  
Antithrombin Activity ◽  
Thrombin Antithrombin Iii Complex

Pure rabbit antithrombin III was isotope labeled (with 125I or 3H) by two different methods; neither procedure caused a loss of antithrombin activity although both methods affected the affinity of the protein for Sepharose-heparin. From segments from freshly excised rabbit aorta, the uptake of isotope-labeled antithrombin III by the endothelium was rapid and saturable, although relatively small compared to the uptake of thrombin; binding of 3H-antithrombin III to the endothelium resembled that of 125I-antithrombin III. Transendothelial passage of antithrombin III into the subendothelial layers (intima-media) was slow and progressive. Endothelium binding was not affected by pretreating the vessel with either heparin, thrombin, or glycosaminoglycan-specific enzymes. Endothelium-bound antithrombin III was not selectively displaced by either heparin or thrombin. In contrast, endothelium-bound thrombin was rapidly dislodged by antithrombin III as a thrombin- antithrombin III complex. The surface of the deendothelialized aorta (ie, subjected to a balloon catheter) bound antithrombin III avidly. Pretreatment of the deendothelialized vessel with glycosaminoglycan- specific enzymes, particularly heparitinase, decreased intima-media binding by up to 80%. 125I-antithrombin III, when bound to the deendothelialized vessel surface, was actively displaced by either heparin, thrombin, or by unlabeled antithrombin III. The relatively poor binding of antithrombin III compared with that of thrombin by the endothelium in vitro supports an earlier proposal (Lollar P, Owen WG: J Clin Invest 66:1222–1230, 1980) that thrombin bound to high-affinity sites, possibly pericellular proteoglycan, of the endothelium is inactivated by plasma antithrombin III in vivo. Such a situation probably holds for large arteries at least.

Quantitation of Platelet Adherence to Rabbit Aortae and Platelet Survival After Two Injuries With a Balloon Catheter

1979 ◽  
Author(s):  
R Kinlough-Rathbone ◽  
H Groves ◽  
S Maric ◽  
M Packham ◽  
J Mustard
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Platelet Adherence ◽  
Platelet Survival ◽  
Single Balloon

Following a single balloon catheter injury to a rabbit aorta (INJ 1) a monolayer of platelets covers the subendothelium within 10 min, the surface becomes relatively nonreactive to further platelet accumulation and platelet survival is not altered. We have now studied whether a second similar injury (INJ 2) of the non-reactive, smooth muscle cell-rich neointima 7 days after INJ 1 makes the surface of the neointima reactive to platelets or alters platelet survival. 51Cr-platelet adherence to the neointima of aortae subjected to INJ 2 in vitro 7 days after an initial in vivo injury was not significantly different from the adherence following a single in vitro injury (16,600 ± 3100 platelets/mm2 and 27,600 ± 4000 respectively, p > 0.2). In vivo adherence of 51Cr-platelets to the surface of rabbit aortae was similar following INJ 1 (0.084 ± 0.009% of the circulating platelets) and INJ 2 (0.130 ± 0.03%, p > 0.2). Platelet survival after injury to the neointima was not significantly different in animals with an undamaged aortic endothelium (74.6 ±5.9 hr and 80.2 ± 4.3 hr respectively, p > 0.5). Thus, a second injury involving the smooth muscle cell-rich neointima that forms after removal of the endothelium with a balloon catheter does not cause more platelets to accumulate than the initial injury, nor shorten platelet survival.

scholarly journals Behavior of plasminogen at the luminal surface of the normal and deendothelialized rabbit aorta in vivo and in vitro

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1260-1267 ◽  
Author(s):  
MW Hatton ◽  
SL Moar ◽  
M Richardson
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Luminal Surface ◽  
Plasmin Activity ◽  
Transmission Electron ◽  
Rapid Adsorption

Abstract The behavior of purified rabbit plasminogen at the luminal surface of the uninjured and deendothelialized rabbit aorta has been studied in vivo and in vitro. After intravenous injection, 125I-plasminogen associated rapidly with the endothelium (approximately 0.1 pmol/cm2 at saturation) and passed through to accumulate in the subendothelium. At two to 15 hours after injection, 11 to 15 times more radioactivity was associated with the subendothelium than with the endothelium. Removal of the endothelium by balloon catheter led to a rapid adsorption of 125I-plasminogen by the luminal surface of the vessel; saturation (9.1 pmol/cm2) was attained at ten to 20 minutes after deendothelialization. Of the adsorbed plasminogen (radioactivity), only 2% to 4% was associated with the adherent platelet monolayer. Uptake of 125I- plasminogen by the deendothelialized vessel was not significantly inhibited by epsilon-aminohexanoic acid whether injected before or after the 125I-plasminogen. No evidence of plasmin activity at the aorta surface was found from either transmission electron microscopy studies or from amidolytic assays of plasminogen-saturated deendothelialized aorta samples before or after urokinase treatment. Balloon catheter treatment in vivo, however, generated significant antiplasmin activity of the deendothelialized aorta surface. We conclude that plasmin formed in vivo is probably inactivated by the antiplasmin activity that is associated with the subendothelium.

U74389F, a 21-aminosteroid antioxidant, improves neoendothelial morphology, but not neointimal thickening after balloon catheter injuryThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

2009 ◽  
Vol 87 (12) ◽  
pp. 1102-1109 ◽  
Author(s):  
Subramanyam N. Murthy ◽  
Donald L. Akers, ◽  
I-Li Chen ◽  
Thomas A. Osgood, ◽  
Raphael Santiago ◽  
...  
Keyword(s):  
Contractile Response ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Arterial Injury ◽  
No Production ◽  
Cardiovascular Research ◽  
Treatment Groups ◽  
No Formation ◽  
Cord Injury ◽  
Inhibit Lipid Peroxidation

U74389F is a compound in a family of 21-aminosteroids devoid of classical glucocorticoid action that inhibit lipid peroxidation. These compounds improve neurologic function and tissue survival after head or spinal cord injury. Dexamethasone inhibits development of intimal hyperplasia (IH) and improves attenuated nitric oxide (NO) production of the rabbit aorta subsequent to balloon catheter injury. We tested the hypothesis that U74389F is protective in a catheter-induced endothelial-denuded and arterial injury model. A 4-Fr Fogarty balloon (BALL) embolectomy catheter was passed through the thoracic aorta of New Zealand White rabbits treated with 15 mg/kg U74389F (LAZ) 2 days before and 1 week after injury. Animals were killed at 4 weeks after surgical intervention, and formation of IH was determined by calculating the intimal/medial ratio (I/M). The treatment groups of animals were injured untreated (BALL), injured treated (BALL/LAZ), uninjured treated (CONTROL/LAZ), and sham-operated treated (SHAM/LAZ). Scanning electron microscopy revealed that after injury lazaroid treatment produced an improvement of the neoendothelium (alignment in the direction of blood and fewer intercellular gaps) as compared with injured but untreated aortas. Relaxation to acetylcholine (NO formation) was impaired in aortic rings from catheterized animals; lazaroid treatment improved the relaxation to 10–6 mol/L acetylcholine but not to lower concentrations. I/M for SHAM/LAZ, BALL, and BALL/LAZ was 0.02 ± 0.02, 21.6 ± 1.6, and 17.2 ± 2.5, respectively; BALL vs. BALL/LAZ, p < 0.06. An increased contractile response to 120 mmol/L KCl was observed after lazaroid treatment. This is the first report of lazaroid-mediated improvement in the neoendothelial morphology, improved neoendothelial NO generation, and augmented hypopolarizing contractile response, but no attenuation in the development of IH.

Angiopeptin enhances acetylcholine-induced relaxation and inhibits intimal hyperplasia after vascular injury

1993 ◽  
Vol 265 (4) ◽  
pp. H1265-H1274 ◽  
Author(s):  
J. T. Light ◽  
J. A. Bellan ◽  
I. L. Chen ◽  
L. L. Longenecker ◽  
W. A. Murphy ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Intimal Hyperplasia ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Somatostatin Analogue ◽  
Vascular Rings ◽  
Relaxing Factor ◽  
New Zealand White Rabbits ◽  
Thoracic And Abdominal ◽  
Balloon Catheter Injury

The effects of the somatostatin analogue, angiopeptin (BIM-23014), on neoendothelial function, as evidenced by formation of prostaglandin (PG) I2 and by acetylcholine-induced relaxation (formation of endothelial-derived relaxing factor), were investigated in the rabbit aorta. A balloon catheter injury of the thoracic and abdominal aorta was induced in New Zealand White rabbits. Animals treated with angiopeptin for 2 or 4 wk were compared with untreated rabbits at 2 or 4 wk after the induction of injury, as well as to sham-operated controls. When the rabbits were killed, vascular rings were assessed for arachidonic acid-stimulated PGI2 formation, acetylcholine-induced relaxation, and the degree of intimal hyperplasia. Vascular rings from animals treated with angiopeptin exhibited enhanced acetylcholine-induced relaxation; however, angiopeptin treatment had no effect on arachidonic acid-stimulated PGI2 formation. Intimal hyperplasia in treated animals was reduced by 36%. Treatment with another somatostatin analogue, BIM-23030, did not enhance relaxation or inhibit intimal hyperplasia. These data suggest that treatment with angiopeptin may inhibit intimal hyperplasia in part by its beneficial effect on neoendothelial function.

scholarly journals Behavior of plasminogen at the luminal surface of the normal and deendothelialized rabbit aorta in vivo and in vitro

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1260-1267
Author(s):  
MW Hatton ◽  
SL Moar ◽  
M Richardson
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Luminal Surface ◽  
Plasmin Activity ◽  
Transmission Electron ◽  
Rapid Adsorption

The behavior of purified rabbit plasminogen at the luminal surface of the uninjured and deendothelialized rabbit aorta has been studied in vivo and in vitro. After intravenous injection, 125I-plasminogen associated rapidly with the endothelium (approximately 0.1 pmol/cm2 at saturation) and passed through to accumulate in the subendothelium. At two to 15 hours after injection, 11 to 15 times more radioactivity was associated with the subendothelium than with the endothelium. Removal of the endothelium by balloon catheter led to a rapid adsorption of 125I-plasminogen by the luminal surface of the vessel; saturation (9.1 pmol/cm2) was attained at ten to 20 minutes after deendothelialization. Of the adsorbed plasminogen (radioactivity), only 2% to 4% was associated with the adherent platelet monolayer. Uptake of 125I- plasminogen by the deendothelialized vessel was not significantly inhibited by epsilon-aminohexanoic acid whether injected before or after the 125I-plasminogen. No evidence of plasmin activity at the aorta surface was found from either transmission electron microscopy studies or from amidolytic assays of plasminogen-saturated deendothelialized aorta samples before or after urokinase treatment. Balloon catheter treatment in vivo, however, generated significant antiplasmin activity of the deendothelialized aorta surface. We conclude that plasmin formed in vivo is probably inactivated by the antiplasmin activity that is associated with the subendothelium.

Fibrin-Rich and Platelet-Rich Thrombus Formation on Neointima: Recombinant Tissue Factor Pathway Inhibitor Prevents Fibrin Formation and Neointimal Development following Repeated Balloon Injury of Rabbit Aorta

1998 ◽  
Vol 80 (09) ◽  
pp. 506-511 ◽  
Author(s):  
Yujiro Asada ◽  
Seiichiro Hara ◽  
Atsushi Tsuneyoshi ◽  
Kinta Hatakeyama ◽  
Atsushi Kisanuki ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Balloon Angioplasty ◽  
Tissue Factor Pathway Inhibitor ◽  
Thrombus Formation ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Severe Injury ◽  
Balloon Injury ◽  
Injury Group ◽  
Tissue Factor Pathway

SummaryThrombus formation and neointimal growth are the critical events in restenosis after balloon angioplasty. However, the responses of diseased vessels to injuries caused by balloon angioplasty have not been well examined. We investigated the thrombus formation and neointimal development following the balloon injury to the previously induced neointima in the rabbit aorta and the effects of recombinant tissue factor pathway inhibitor (rTFPI) on these responses. Rabbit thoracic aortas were subjected to injury with a Fogarty 4F balloon catheter at 1.75 atm (first injury), and 4 weeks later the same vessels were subjected to the second injury with a Swan-Ganz 5F balloon catheter at 1.4 atm (mild-injury group) or 1.8 atm (severe-injury group), and immediately after that a retrograde bolus injection of rTFPI (100 μg/kg body weight) or saline was performed into the injured segments via the central tube of the Swan-Ganz catheter. Twenty minutes after the second injury, the injured surfaces were covered with platelet-rich thrombi in the mild-injury group and with fibrin-rich thrombi in the severe-injury group. Damaged intimal smooth muscle cells, which were immunohistochemically positive for tissue factor (TF), were observed beneath the fibrin-rich thrombi. The neointima 4 weeks after the second injury was significantly thicker in the severe-injury group than in the mild-injury group. The bolus infusion of rTFPI markedly inhibited fibrin formation on the injured surfaces, and significantly reduced the neointimal development in the severe-injury group at 4 weeks after the second injury. These results indicate that TF-dependent coagulation pathway is primarily responsible for fibrin-rich thrombus formation and may play an important role in neointimal development following the balloon injury to the rabbit aortic neointima. Additionally the bolus administration of rTFPI to the injured vessels could prevent mural thrombus formation and neointimal growth after balloon angioplasty.

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