Effect of Gram-Negative Endotoxin on Pulmonary Circulation

Kuida, Hiroshi; Hinshaw, Lerner B.; Gilbert, Robert P.; Visscher, Maurice B.

doi:10.1152/ajplegacy.1958.192.2.335

Cited by 127 publications

(33 citation statements)

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“…Our initial studies confirmed earlier work (Kuida, Hinshaw, Gilbert & Visscher, 1958;Kuida, Gilbert, Hinshaw, Brunson & Visscher, 1961) which showed that an acute pulmonary vasoconstriction occurred. This resulted in pulmonary oedema and right ventricular failure and was immediately lethal in approximately half of the cats.…”

Section: Introductionsupporting

confidence: 90%

Further observations on mesenteric vasoconstriction, survival and the clotting defect after endotoxin administration

Cohen¹,

Greenway²,

Innes³

et al. 1973

British J Pharmacology

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Summary1. The initial response after endotoxin administration (3 mg/kg) in cats involved pulmonary vasoconstriction. This was not seen when endotoxin was given by slow infusion and it could be prevented after a bolus injection of endotoxin by pretreatment of the cats with aspirin (10 mg/kg). Intense mesenteric vasoconstriction occurred in all the cats. 2. The mesenteric vasoconstriction was a specific response of the mesenteric blood vessels. At the time the mesenteric bed constricted, the renal bed dilated, the hepatic arterial bed remained unchanged and the smooth muscle of the intestinal wall relaxed. 3. Arterial blood from cats with a fully developed mesenteric vasoconstriction after endotoxin administration was perfused through a normal intestine. No immediate vasoconstriction developed but the perfused intestine constricted slowly over 60 minutes. This suggests that mesenteric constriction was not due to circulating vasoconstrictor factors or the intestinal innervation, but involved a slow local mechanism within the intestine. It could not be prevented or reversed by a variety of pharmacological agents. 4. These observations suggest that endotoxin caused a unique type of mesenteric vasoconstriction in cats by a local mechanism which took up to 60 min to develop, was sufficiently potent to reduce mesenteric flow to <30% control, and was maintained until death of the cats. Blood from these animals did not clot when placed in a glass tube. 5. The mesenteric constriction and the clotting defect could be prevented by repeated administration of aminophylline and dextran solution before and after a bolus intravenous injection of endotoxin. Arterial pressure and mesenteric flow were maintained for at least 10 h in these experiments. Inadequate treatment intensified rather than reduced the intestinal mucosal damage. 6. Cats were treated with aspirin, endotoxin and the optimal regimen for prevention of the mesenteric constriction and allowed to recover from the anaesthetic agent. In this series, 63% survived indefinitely compared to 25% after aspirin and endotoxin treatment and 0% after endotoxin alone. 7. The possible mechanisms of action of aspirin and aminophylline-dextran solution are discussed. Our failure to obtain 100% survival is probably due to pulmonary damage which develops 10-24 h after endotoxin administration. This delayed pulmonary action of endotoxin is not prevented by aspirin M. M. Cohen and others treatment and it seenis unlikely that aspirin will be of any value in the treatment of the pulmonary lesion in man.

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Section: Introductionsupporting

confidence: 90%

Further observations on mesenteric vasoconstriction, survival and the clotting defect after endotoxin administration

Cohen¹,

Greenway²,

Innes³

et al. 1973

British J Pharmacology

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“…Although our data do not define the mechanism responsible for differences in systemic and pulmonary vascular behavior, the possible role of serotonin release during the pyrogen reaction merits consideration (11,27). Our studies in man contrast with Kuida's demonstration of marked postcapillary pulmonary hypertension in animals (17). Aside from the possible effects of species variation and quite dissimilar experimental conditions, the differences may be attributed to the fact that the doses of pyrogen used by Kuida were massive when compared to those used in the present study.…”

Section: Discussionmentioning

confidence: 59%

“…However, data concerning respiratory gas exchange, pulmonary hemodynamics, and arterial blood gas composition in hyperpyrexia are rather fragmentary and inconclusive (7)(8)(9)(12)(13)(14)(15)(16)(17).…”

mentioning

confidence: 99%

Cardiopulmonary Consequences of Pyrogen-Induced Hyperpyrexia in Man*

Moser¹,

Perry²,

Luchsinger³

1963

J. Clin. Invest.

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The physiologic consequences of hyperpyrexia attracted considerable interest when artificiallyinduced fever was a popular therapeutic maneuver (1-10). Although induced hyperpyrexia has lapsed from therapeutic favor, the effects of body temperature elevation in response to infection, environmental factors, or pyrogenic drugs remain a source of concern, especially in patients with cardiac or pulmonary dysfunction.Prior investigations have indicated that fever, whether induced by external heating or pyrogen injection, is accompanied by significant cardiac and peripheral hemodynamic alterations in both animals and man (1-4, 10, 11). However, data concerning respiratory gas exchange, pulmonary hemodynamics, and arterial blood gas composition in hyperpyrexia are rather fragmentary and inconclusive (7)(8)(9)(12)(13)(14)(15)(16)(17).The purpose of this study was to evaluate simultaneously the changes in body temperature, pulmonary and systemic hemodynamics, respiratory gas exchange, and arterial blood gas composition that occur in normal subjects after the intravenous injection of a pyrogenic lipopolysaccharide extract of gram-negative bacilli. Since prior studies in man have not included cardiac catheterization and detailed measurement of respiratory function, it was felt that an investigation using the techniques now available would shed further light upon the cardiopulmonary consequences of the pyrogenic reaction in man. MATERIALS AND METHODSTen male subj ects ranging from 33 to 74 years of age (mean 45.6) were studied. All were free of cardiac and pulmonary disease by clinical and routine laboratory criteria. All subjects were studied in the morning after *Aided by grants H-3114 and H-6236 from the Na-

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“…Since the pump-perfused lobe in the present study was not dissected or excised, and was perfused with blood which recirculated through the entire body of the animal, these lobar vessels might have been more sensitive to small differences in vasoactive substances than were the excised lobes in the previous study (10). Other studies (24) have shown that the pressor responses of the separated lobar vessels in this preparation to similar quantities of serotonin were greater than those reported with that excised lobe preparation (25) (26), and injections of fibrinopeptides (27), and endotoxin (28).…”

Section: Discussionmentioning

confidence: 66%

The pulmonary vasopressor response to decreases in blood pH in intact dogs

Hyman¹,

Woolverton²,

Guth³

et al. 1971

J. Clin. Invest.

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A B S T R A C T The pulmonary vasopressor response to acidemia was studied in intact dogs in a hemodynamically separated lobe which was pump perfused with systemic arterial or venous blood at a fixed rate. The magnitudes of the lobar vasopressor responses to perfusion with blood rendered acidic by infusions of hydrochloric lactic, and acetic acids, and by hypercapnia (membrane oxygenator) were significantly different. Although the PH of the perfusing blood in each group fell to similar extents (pH 7.1-7.0), the lobar pressor response was greatest with hydrochloric acid (HCl), smaller with lactic and acetic acids, and absent with hypercapnia. A lobar vasopressor response also occurred during lobar perfusion with blood which -had been extracorporeally acidified with HCO or acetic acid, but then returned to control pH by infusions of sodium bicarbonate and Tris before reaching the lung. A lobar vasopressor response also resulted from pump perfusion of the lobar artery with femoral venous blood during perfusion of the isolated ipsilateral femoral artery with similarly treated aortic blood. However, no lobar vasopressor response resulted from pump perfusion of the lobar artery with blood removed transseptally from a right pulmonary vein during acidification (HCl) of the right pulmonary artery (to pH 7.0).The data indicate that, in this experimental preparation involving closed-chest dogs spontaneously breathing air or 35% oxygen, the lobar vasopressor response to infusions of acidifying agents is not directly related to the pH of blood actually perfusing the lobar vessels. Additionally, the vasopressor response is prevented by prior perfusion of the acidified blood through a pulmo-

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Effect of Gram-Negative Endotoxin on Pulmonary Circulation

Cited by 127 publications

References 0 publications

Further observations on mesenteric vasoconstriction, survival and the clotting defect after endotoxin administration

Further observations on mesenteric vasoconstriction, survival and the clotting defect after endotoxin administration

Cardiopulmonary Consequences of Pyrogen-Induced Hyperpyrexia in Man*

The pulmonary vasopressor response to decreases in blood pH in intact dogs

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