Pulmonary microembolism: A cause of lung injury

Beal, Sandra L.; Reed, RoseMary; Heimbach, David M.; Chi, Emil; Reynolds, Larry O.

doi:10.1016/0022-4804(87)90086-2

Cited by 4 publications

(12 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding raised the possibility that endogenous platelets are incorporated into the clot during its growth and extension in vivo. In support of this notion, we found that intravenous injection of 10 mg/kg MAb 7E3 F(abЈ) 2 enhanced the dissolution of 125 I-ME by 20-25% (Fig. 8A).…”

supporting

confidence: 61%

“…The following materials were used: Iodogen from Pierce (Rockford, IL), Na 125 I from NEN Life Sciences (Boston, MA), fatty acid-free bovine serum albumin (BSA) from Boehringer-Mannheim (Indianapolis, IN), human thrombin and epinephrine from Sigma (St. Louis, MO), horse collagen (type I) from Chrono-Log (Havertown, PA), human recombinant tissue-type plasminogen activator (tPA, Activase) from Genentech (San Francisco, CA), fibrinogen (Fg; FIB 1, 1310) from Enzyme Research Laboratories (South Bend, IN), Retavase (a mutant form of human tPA that lacks kringle and growth factor domains), and murine monoclonal antibody that cross-reacts with human and rat platelet glycoprotein IIb/IIIa complex [MAb 7E3 F(abЈ) 2] from Centocor (Malvern, PA). Adult Sprague-Dawley male rats (200-350 g) and BALB/c mice were used following a protocol approved in writing by the University of Pennsylvania Institutional Animal Care and Use Committee.…”

Section: Methodsmentioning

confidence: 99%

“…Finally, we injected rats with ME followed by a low dose of Retavase (10 g/kg), 7E3 F(abЈ) 2 (6 mg/kg), or both. Figure 8B shows that addition of 7E3 F(abЈ) 2 enhanced Retavase-induced fibrinolysis by 50%.…”

mentioning

confidence: 99%

“…In contrast, pulmonary deposition of microemboli (ME) often does not cause acute symptoms (silent ME). Nevertheless, pulmonary ME is a relatively common accompaniment to acute lung injury (adult respiratory distress syndrome), hyperoxia, bleomycin toxicity, sepsis, trauma, surgery on the lower extremities, and angioplasty (2,21,30,33,36,39,40,44,52,53). Microembolism may lead to inflammation and edema acutely and contribute to the development of pulmonary fibrosis and hypertension over time (4,9,22,27,31).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Platelets inhibit the lysis of pulmonary microemboli

Murciano

Harshaw

Neschis

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Using tracings of 125 I-labeled fibrin(ogen) in rodents, we examined the hypothesis that platelets impede the lysis of pulmonary emboli.125 I-Microemboli (ME, 3-10 micron diameter) lodged homogeneously throughout the lungs after intravenous injection in both rats and mice (60% of injected dose), caused no lethality, and underwent spontaneous dissolution (50 and 100% within 1 and 5 h, respectively). Although lung homogenates displayed the most intense fibrinolytic activity of all the major organs, dissolution of ME was much slower in isolated perfused lungs (IPL) than was observed in vivo. Addition of rat plasma to the perfusate facilitated ME dissolution in IPL to a greater extent than did addition of tissue-type plasminogen activator alone, suggesting that permeation of the clot by plasminogen is the rate-limited step in lysis. Platelet-containing ME injected in rats lysed much more slowly than did ME formed from fibrin alone.125 I-Thrombi, formed in the pulmonary vasculature of mice in response to intravascular activation of platelets by injection of collagen and epinephrine, were essentially resistant to spontaneous dissolution. Moreover, injection of the antiplatelet glycoprotein IIb/IIIa antibody 7E3 F(abЈ) 2 facilitated spontaneous dissolution of pulmonary ME and augmented fibrinolysis by a marginally effective dose of Retavase (10 g/kg) in rats. These studies show that platelets suppress pulmonary fibrinolysis. The mechanism(s) by which platelets stabilize ME and utility of platelet inhibitors to facilitate their dissolution deserves further study. pulmonary embolism; plasminogen activators; platelets; fibrinolysis; animal model; glycoprotein IIb/IIIa THE LUNG SERVES as a natural filter for thromboemboli of diverse sizes (12). Thrombotic occlusion of the main or lobar pulmonary arteries by large clots (massive pulmonary embolism, PE) is a common cause of morbidity and mortality (15,20). In contrast, pulmonary deposition of microemboli (ME) often does not cause acute symptoms (silent ME). Nevertheless, pulmonary ME is a relatively common accompaniment to acute lung injury (adult respiratory distress syndrome), hyperoxia, bleomycin toxicity, sepsis, trauma, surgery on the lower extremities, and angioplasty (2,21,30,33,36,39,40,44,52,53). Microembolism may lead to inflammation and edema acutely and contribute to the development of pulmonary fibrosis and hypertension over time (4,9,22,27,31).The treatment of PE, as with other venous thromboembolic conditions, is typically restricted to agents such as heparin that retard fibrin clot formation, with a relatively limited use of agents that promote fibrinolysis. Despite the effectiveness of such therapy, PE remains a common cause of mortality and morbidity. Thus there is a continuing need for more effective means to prevent and treat both PE and ME, based on a more thorough understanding of the mechanisms that regulate clot dissolution in the lung.For example, the role of platelets in PE and ME has received relatively little study. Recently, it has been shown tha...

show abstract

supporting

confidence: 61%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Platelets inhibit the lysis of pulmonary microemboli

Murciano

Harshaw

Neschis

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Studies on experimentally induced pulmonary microthrombi in dogs have reported a significant drop in circulating platelet concentration with increased neutrophils and platelets within the pulmonary capillaries, increased mean pulmonary artery pressure and embolirelated arterial dilation, increased microvascular permeability to protein and severe lung injury. [22][23][24] In addition, microthrombi and tumour-cell emboli have been reported to result in localized ischemia and tissue hypoxia, both of which are directly linked to cancer metastasis through hypoxia-inducible factor target gene expression, inhibition of the transmembrane molecule E-cadherin, enhanced proteolytic activity at the tumour invasive front and increased cell motility towards the blood or lymphatic microcirculation. 40,42,49 No prevalence studies of microthrombi in canine solid tumours have previously been reported, making results of this study difficult to compare, but the true prevalence is likely higher than the 2.6% reported here.…”

Section: Discussionmentioning

confidence: 99%