Humoral Transmission of Cardiorespiratory Changes in Experimental Lung Embolism

Halmagyi, D; Starzecki, B.; Horner, G. J.

doi:10.1161/01.res.14.6.546

Cited by 47 publications

(20 citation statements)

References 15 publications

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“…2 h after embolus, VDp/VT was 22% (Table II), while (1,11,12). Present investigations show that emboli cause production of the antiaggregator and vasodilator PGI2, as well as the proaggregator and constrictor, TxA2.…”

Section: Introductionmentioning

confidence: 48%

“…Pulmonary embolism produces cardiopulmonary dysfunction that may result directly from mechanical obstruction of the pulmonary vasculature as well as indirectly by humoral factors (1). It is believed that platelet interaction with a clot leads to platelet release reaction, which may be responsible for several of the attendant cardiopulmonary abnormalities such as pulmonary hypertension and increase of venous admixture (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…Cardiopulmonary function has also been shown to be altered in other states where platelets are entrapped in the lungs such as microembolism, sepsis, and abdominal aortic aneurysm repair (1,11,14,15,25,26). In addition to platelet synthesis of TxA2, the observation that lung parenchyma can be stimulated by antigen antibody reaction to release thromboxanes (27) indicates that pulmonary metabolic events may also influence cardiopulmonary function.…”

Section: Introductionmentioning

confidence: 99%

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Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Utsunomiya¹,

Krausz²,

Levine³

et al. 1982

J. Clin. Invest.

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A B S T R A C T Humoral factors released from platelets during pulmonary embolism may be the cause of several attendant cardiopulmonary abnormalities. This study examines the role of thromboxanes (Tx) after experimental embolism induced with 0.5 g/kg autologous clot in four groups of five dogs: (a) untreated embolized controls; (b) pretreatment with the Tx synthetase inhibitor, imidazole 25 mg/kg -h i.v., starting 30 min before embolization; (c) pretreatment with the cyclooxygenase inhibitor indomethacin, 5 mg/kg, 12 h per os and 1 mg/kg, 1 h i.v. before the experiment; (d) treatment with prostacyclin (PGI2) 100 qg/kg. min i.v. for 1 h, 1 h after embolization. Within 30 min, embolization led to increases of 6-keto-PGF,a, the stable hydrolysis product of PGI2, from 0.11±0.08 ng/ml (mean±SD) to 0.33±0.10 7g/ml (P < 0.005) and TxB2, the stable product of TxA2, from 0.10±0.04 qg/ml to 0.38±0.0611g/ml (P < 0.001). Increases were observed in total dead space (VD/VT) from 0.46±0.03 to 0.61±0.08 (P < 0.025, physiologic shunting (Qs/(T) from 16±4% to 38±9% (P < 0.01), pulmonary vascular resistance (PVR) from 2.27±0.59 mm Hg.min/liter to 9.21±1.90 mm Hg* min/liter (P < 0.005) and mean pulmonary arterial pressure from 14±6 mm Hg to 34±1 mm Hg (P < 0.001). Cardiac index (CI) fell from 139±11 ml/kg.min to 95±17 ml/kg.min in 4h (P < 0.025). Imidazole pretreatment prevented a rise of TxB2, but not 6-keto-PGFj,; indomethacin blocked both. Both agents maintained VD/VT at base line and limited increases in Qs/QT and PVR. CI was higher after imidazole pretreatment compared with controls (P < 0.025). < 0.025), QS/QT (P < 0.025) and PVR (P < 0.05) within 30 min. During PGI2 infusion, CI was higher than controls. Concentrations of TxB2 correlated with VD/VT, r = 0.79 and Qs/QT, r = 0.69 (P < 0.001).Treatment of three dogs with the imidazole derivative ketoconazole, 10 mg/kg IV, 30 min after 0.75 g/kg autologous clot resulted in a lowering of physiologic dead space, but no other improvement of cardiopulmonary function. These results show that a number of cardiopulmonary abnormalities induced by pulmonary embolism are related directly or indirectly to platelet secretions and that VD/VT is closely allied to TxA2 levels.

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Section: Introductionmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Utsunomiya¹,

Krausz²,

Levine³

et al. 1982

J. Clin. Invest.

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“…The decrease in pulmonary compliance has been shown to be dependent on the release of humoral substances (Halmagyi, Starzecki & Homer, 1964). Such humoral agents, with known bronchoconstrictor actions have been thought to be histamine (Nadel, et al 1964), 5-hydroxytryptamine (5-HT); (Thomas, Stein, Tanabe, Rege & Wessler, 1964) or prostaglandin-like substances (Nakano & McCloy, 1973).…”

Section: Introductionmentioning

confidence: 99%

The role of prostaglandins in the bronchoconstriction induced by pulmonary micro‐embolism in the guinea‐pig.

Clay¹,

Hughes²

1980

The Journal of Physiology

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SUMMARY1. Respiratory resistance was measured by a forced oscillation technique in vagotomized guinea-pigs before and after pulmonary micro-embolism produced by i.v. injection of 0 5 ml./kg of 10 % w/v BaSO4. Changes in quasi-static inspiratory compliance and arterial platelet count were also measured.2. Micro-embolic challenge with BaSO4 increased respiratory resistance by 27 %; this was abolished by prior treatment with indomethacin; no change in the control resistance occurred after indomethacin.3. No change in respiratory compliance or arterial platelet numbers were observed following low dose BaSO4 micro-embolism. This suggests that pulmonary microembolism produced a decrease in medium or large airway calibre, which was mediated by a prostaglandin-like substance from lung tissue, and did not require the presence of the vagus nerves.

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“…In addition, FII a did not impair the coagulation pathways. APT can produce severe cardiopulmonary dysfunction that is characterized by pulmonary arterial hypertension, right ventricular failure, and hypoxemia, which is the principal cause of APT-related death [19][20][21][22] . In addition, the major adverse effect is attributed to the direct mechanical obstruction of the pulmonary arteries.…”

Section: Discussionmentioning

confidence: 99%

The effect of the fibrinolytic enzyme FIIa from Agkistrodon acutus venom on acute pulmonary thromboembolism

Lin¹,

Liang

Tang³

et al. 2011

Acta Pharmacol Sin

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npg IntroductionAcute pulmonary thromboembolism (APT) is defined as an embolic occlusion of a pulmonary artery, which results in a sudden increase in pulmonary resistance, right ventricular afterload, and O 2 consumption with a reduction in right coronary artery perfusion [1] . Despite advances in diagnosis and therapy, the mortality associated with APT remains high [2,3] . Various approaches are available for the treatment of APT, including anticoagulant drugs and thrombolytic agents. Anticoagulant therapy, such as heparin, is thought to enhance the effect on thrombolysis by preventing formation of new thrombi [4,5] . However, anticoagulants have minimal effects on previously existing thrombi. Enhanced fibrinolysis prevents disturbances in the circulation to organs by dissolving thrombi. It may be reasonable to assume that fibrinolytic therapy is effective against APT [6][7][8][9][10] . Current thrombolytic agents, such as tissue plasminogen activator (t-PA) and urokinase, which act as plasminogen activators, are effective at dissolving intravascular thrombi. These agents act indirectly on the thrombi by converting plasminogen, both circulating and fibrin-bound, into plasmin, which is the primary enzyme responsible for the removal of emboli. These conditions may "overflow" the systemic circulation and lead to systemic fibrinolysis and degradation of other clotting proteins [11] , which may increase the bleeding tendency or may result in local activation of coagulation.FII a is a novel fibrinolytic enzyme that is purified from Anhui Agkistrodon acutus venom and is a type of snake venom metalloproteinase. Based on its crystal structure, binding to ZnP 2+ is known to be essential for it hydrolytic activity [12,13] . We have demonstrated that FII a has the ability to directly degrade fibrin in vitro and effectively dissolve thrombi in vivo Aim: To evaluate the effects of the fibrinolytic enzyme FII a from Agkistrodon acutus venom on acute pulmonary thromboembolism (APT) in animal models. Methods: Both rabbit and dog APT models were used. For the rabbit APT model, the thrombi weight before and after administration was measured. Central venous pressure (CVP) and mean arterial pressure (MAP) were measured before and 15, 30, 60, and 120 min after the injection of the blood clot. Partial thromboplastin time (APTT), prothrombin time (PT), platelet count, and fibrinogen concentration were measured using auto analyzers. Plasminogen activity was measured based on chromogenic substrates. In the dog APT model, pulmonary blood flow was recorded using pulmonary angiography. Results: Intravenous administration of FIIa (0.1-5.0 mg/kg) improved the APT-induced hemodynamic derangements and reduced thrombi weight. The angiography evidence also showed that the pulmonary emboli had almost disappeared after FII a infusion. FII a (0.1, 0.5, or 1.0 mg/kg) did not impair the coagulation pathways, although very high doses of FII a (5.0 mg/kg) could stimulate the production of plasminogen and result in impairment of the pathways. Conclusion...

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Humoral Transmission of Cardiorespiratory Changes in Experimental Lung Embolism

Cited by 47 publications

References 15 publications

Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Thromboxane Mediation of Cardiopulmonary Effects of Embolism

The role of prostaglandins in the bronchoconstriction induced by pulmonary micro‐embolism in the guinea‐pig.

The effect of the fibrinolytic enzyme FIIa from Agkistrodon acutus venom on acute pulmonary thromboembolism

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