Mechanism of bronchoconstriction produced by thromboemboli in dogs

Thomas, Duncan P.; Stein, Martin H.; Tanabe, Genzo; Rege, Vishram B.; Wessler, Stanford

doi:10.1152/ajplegacy.1964.206.6.1207

Cited by 106 publications

(25 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…~.,0 The mechanisms responsible for this effect are not clear but they include hypoxia; 1 hypocapnia; z5 release of prostaglandins z6 or serotonin. 18 The role of any one of these factors or the interplay between them is also not clear, but our experiments suggest that agents which interfere with either prostaglandin synthesis or serotonin action have additive effects in reducing the hypotension which occurs following embolism. Although the doses of aspirin used in this study are high compared with those used to block prostaglandin synthesis in the platelet z7 we have previously demonstrated that doses of aspirin in excess of 100 rag.…”

Section: Figurementioning

confidence: 79%

The effects of aspirin and methysergide, singly and in combination, on systemic haemodynamic responses to pulmonary embolism

Todd

Forrest

Cragg

1981

Canad. Anaesth. Soc. J.

View full text Add to dashboard Cite

Pretreatment of anaesthetized rabbits with aspirin (A), 250mg.kg -I, methysergide (M) 3 mg. kg -~ or a combination of both (A + M) was done before pulmonary embolism with a 1.0 ml autologous blood clot and compared with no pretreatment (C). Experiments were done until 10 survivors were present in each group. Mortality rate in controls (C) was 55 per cent (death in less than 30 minutes) compared to zero in (A) and (A + M) and nine per cent in (M). Arterial blood pressure fell to 60 per cent ofpre-embolism values two minutes after embolism in (C) but had returned to 85 percent of pre-embolism values after 60 minutes. This compares with a drop to 82 per cent at two minutes and 83 per cent at 60 minutes in (A), a drop to 70 per cent at two minutes and 90 per cent at 60 minutes in (M) and a very small drop to 92 per cent at two minutes which was unchanged at 60 minutes in (A + M). Right ventricular pressure increased by 75 per cent after two minutes compared to pre-embolism values in (C) and was still elevated by 37 per cent after 60 minutes. This compares with increases at two minutes and 60 minutes respectively of 58 and 23 per cent in (A), 65 and 35 per cent in (M) and 55 and 18 per cent in (A + M). Heart rate did not show any significant changes in any of the groups after embolism.These results show a dramatic reduction in mortality from pulmonary embolism with aspirin or methysergide pretreatment, which is associated with significant attenuation of the hypotensive response seen in controls. These agents may act by inhibiting the actions of a release of prostaglandins and serotonin. The additive effects of the combination used suggests that both mediators may play a role in the haemodynamic responses to pulmonary embolism. Canad. Anaesth. Soc. J., vol. 28, no. 4, July 1981 to stabilize the cardiorespiratory system, improve left ventricular filling and increase pulmonary blood flow. 6 Several factors may contribute to the reduced pulmonary blood flow: mechanical obstruction by the embolus, local release of humoral pulmonary vasoconstrictor substances and reflex vasoconstriction. Some workers have attributed the pulmonary vascular effects solely to mechanical obstruction by the embolus. ~'7's Others have commented on the discrepancy between the degree of obstruction and the resulting haemodynamic outcome, both in man 9 and in experimental animals, t~ These observations may be accounted for in part by pulmonary vasoconstriction resulting from the release of humoral mediators.Humoral substances which may be responsible for the pulmonary vasoconstriction include prostaglandins, histamine and serotonin, t H3 Inhibitors of the synthesis of prostaglandins have been shown to decrease the pulmonary vascular pressor response following embolization with a small blood clot introduced into a lobar pulmonary artery. ~4 In addition, pretreatment of animals with high doses of aspirin reduced the mortality 373

show abstract

Section: Figurementioning

confidence: 79%

The effects of aspirin and methysergide, singly and in combination, on systemic haemodynamic responses to pulmonary embolism

Todd

Forrest

Cragg

1981

Canad. Anaesth. Soc. J.

View full text Add to dashboard Cite

show abstract

“…It was postulated that hypocapnea subsequent to the loss of perfusion resulted in bronchiolar constriction, and in some areas complete airway closure with atelectasis, and that these mechanical changes were responsible for the shift in ventilation away from the nonperfused lung. Recent data have suggested that the bronchoconstriction subsequent to experimental pulmonary thromboembolism produced by autogenous thromboemboli is related to the release of humoral agents from the platelets coating the thromboembolus (17). Moore, Humphreys, and Cochran, in dogs, also found that ventilation to a nonperfused lung decreased (5).…”

Section: Methodsmentioning

confidence: 99%

Ventilation-perfusion abnormalities in experimental pulmonary embolism.

Levy¹,

Stein²,

Totten³

et al. 1965

J. Clin. Invest.

View full text Add to dashboard Cite

The changes in pulmonary function that occur as a result of experimental pulmonary vascular occlusion have been intensively investigated. The techniques employed for producing pulmonary vascular occlusion have included balloon occlusion (1-3) and the injection of particulate matter (4) into the pulmonary artery. The results of such studies are not directly comparable to clinical pulmonary thromboembolism, where vascular occlusion is produced by autogenous thrombi. It might be anticipated, a priori, that substantial differences would occur because of the different physicochemical nature of the embolic material and the different pattern of embolization. In the present studies the effects of autogenous thromboemboli on ventilation-perfusion relationships, pulmonary gas exchange, pulmonary mechanics, and the ultrastructure of the lung are described.Two questions related to pulmonary thromboembolism are of particular interest. First is the problem of redistribution of ventilation after embolization. Several investigators have described a shift of pulmonary ventilation away from nonperfused lung segments after balloon occlusion of a pulmonary artery (1,5,6). We have developed a technique to evaluate whether redistribution of ventilation occurs after autogenous pulmonary thromboembolism. Second is the evaluation of the mechanisms resulting in arterial hypoxemia after autogenous pulmonary thromboembolism.* Submitted for publication December 22, 1964; accepted July 1, 1965. This work was supported in part by grants HE-05059 and HE-05317 from the National Institutes of Health and in part by a grant from the Tuberculosis League of Pittsburgh. MethodsSixty-five healthy, mongrel dogs ranging in weight from 9 to 26 kg were studied. The animals were anesthetized with either pentobarbital, thiopental sodium, or chloralose by intravenous administration and intubated with an endotracheal tube. Thirty-four dogs were studied during spontaneous ventilation (spontaneous ventilation dogs, SVD), and in 31 dogs spontaneous ventilation was abolished by either d-tubocurarine or succinylcholine administered intravenously, and ventilation was then maintained with an Etsten bellows pump set to deliver a constant tidal volume at a constant frequency (controlled ventilation dogs, CVD). The total amount of barbiturate administered was such as previously observed to maintain adequate anesthesia in nonparalyzed animals. Autogenous thrombi were produced and released into the pulmonary circulation as previously described (7).The following measurements were made before and within 30 minutes after embolization in the SVD and CVD while they were breathing room air. Minute ventilation (VE) was measured by standard techniques. Femoral arterial blood was analyzed for oxygen content and capacity, and C02 content by the technique of Van Slyke and Neill (8). Arterial pH was measured with a glass electrode at 37°C. Plasma C02 content was derived with the correction factors of Van Slyke and Sendroy from the whole blood CO2 content, the arterial hematocrit,...

show abstract

“…Indeed, it would be of interest to examine the degree of platelet capture by the lung following a high dose of BaSO4 microparticles. Massive embolization may lead to the trapping of platelets after aggregation, with the subsequent release of 5-HT, which would produce a decrease in lung compliance (Thomas et al 1964). It is conceivable that platelet aggregation, under these circumstances, occurs as a result of massive haemostasis.…”

Section: Efects Of Indomethacinmentioning

confidence: 99%

“…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). In addition, platelet aggregation, occurring as a result of microsphere embolization, may lead to the release of humoral agents such as 5-HT (Zucker & Grant, 1974) and prostaglandins (Bo, Hognestad & Vaage, 1974;Vaage & Piper, 1975).…”

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

View full text Add to dashboard Cite

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.

show abstract

Mechanism of bronchoconstriction produced by thromboemboli in dogs

Cited by 106 publications

References 0 publications

The effects of aspirin and methysergide, singly and in combination, on systemic haemodynamic responses to pulmonary embolism

The effects of aspirin and methysergide, singly and in combination, on systemic haemodynamic responses to pulmonary embolism

Ventilation-perfusion abnormalities in experimental pulmonary embolism.

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

Contact Info

Product

Resources

About