Björn Revenäs

Rapid invivo metabolism of Leukotriene C3 in the monkey, Macacairus

Abstract [5,6,8,9,11,12-3H6] Leukotriene C3 (5 μCi) was injected through a catheter into the right atrium of an anesthetized male monkey. Blood samples were drawn from the aorta via a second catheter. The concentration of tritium in blood decreased from 100 nCi/ml after 5 sec to 1 nCi/ml 15 min after injection, suggesting that leukotriene C3 was rapidly eliminated from the circulation. Chromatographic analyses of radioactive material in blood collected before recirculation had occurred (15 sec after injection) demonstrated that 40% of the radioactive material had been converted into two less polar metabolites. These products had the same chromatographic properties as leukotrienes D3 and E3, respectively. The results indicate that leukotriene C3 is rapidly transformed by monkey lung in vivo . Two minutes after injection, the component corresponding to leukotriene E3 was the predominating metabolite in blood.

Aggregate Anaphylaxis in the Monkey

Haematological and histological studies were made following challenge in 8 monkeys (Macaca irus) sensitized with ovalbumin. Haemagglutinating, but no reaginic antibodies to ovalbumi

Anaphylaxis in the Monkey: Respiratory Mechanics, Acid‐base Status and Blood Gases

Aggregate anaphylaxis was induced by intravenous injection of the specific antigen in eight ovalbumin‐sensitized monkeys. Changes in respiratory mechanics, acid‐base status and blood gases were studied during the following half hour. Within 1 minute after challenge, a short period of respiratory depression, probably reflex‐mediated, was observed. This was followed by hyperventilation, and arterial Pco2 decreased. There was a rapid increase in pulmonary resistance (Rpulm) and a concomitant decrease in pulmonary dynamic compliance (Cdyn), suggesting constriction of smooth muscles in the lung. Rpulm returned to the control value but Cdyn remained depressed, as a result of constriction of small airways and pulmonary congestion. Oxygen saturation in arterial blood decreased slightly due to a marked destruction of mixed venous blood and increased venous admixture. Progressive metabolic acidosis developed, indicating poor tissue oxygenation and perfusion. The changes observed in this study were not severe enough to cause any major disturbance of the gas exchange in the lungs, despite a severe anaphylactic shock.

Histopathological lung changes in immune complex mediated anaphylactic shock in humans elicited by dextran

Severe dextran-induced anaphylactic reaction (DIAR) is being recognized as a form of immediate IgG mediated immune complex reaction. Support for this pathogenesis is found in the correlation between the titer of dextran-reactive antibodies of IgG class and the severity of the reaction. Autopsy records were reviewed in 27 certified cases of fatal DIAR. The most frequent macroscopic findings were dilatation of the right side of the heart and acute pulmonary stasis. Autopsy lung specimens were collected from 17 of these patients. In 15 of the 17 lung specimens pulmonary microemboli were found. The microemboli had the appearance of hyaline eosinophilic globules, and the lung vasculature also contained leukocytes, platelets and disintegrated erythrocytes. These findings show similarity to the findings in a monkey model of known IgG mediated anaphylaxis, and give further support to the proposed pathogenesis of severe DIAR.

Anaphylaxis in the Monkey: Pulmonary Oedema after Pre-treatment with β-Receptor Stimulants

Aggregate anaphylaxis was induced in seven ovalbumin‐sensitized monkeys, with high titres of ovalbumin specific haemagglutinating antibodies. After pre‐treatment with an intravenous (i.v.) injection of 0.25 mg/kg terbutaline (n = 6) cr an infusion of isoprenaline (n = 1), anaphylactic shock was induced by i.v. challenge with specific antigen. Haemodynamics, regional blood flows, respiratory mechanics, blood gases and haematological changes were studied during the following 30 min. Severe shock developed following ovalbumin challenge and the cardiac output was reduced by a mean of 74%. Pulmonary vascular resistance increased 11‐fold. Pulmonary dynamic compliance decreased, but there was only a minor increase in pulmonary resistance. Hypoxaemia and severe metabolic acidosis developed. Circulating platelets and leucocytes decreased markedly. Three animals died with fulminant pulmonary oedema. In conclusion, the reaction pattern was similar to that found in studies of monkeys that received no prior treatment. However, the occurrence of pulmonary oedema suggests that the effects of large doses of terbutaline on the heart, combined with the high pulmonary vascular resistance, resulted in more severe pulmonary changes than took place in untreated animals.

TWO CARDIORESPIRATORY PATTERNS OF ANAPHYLAXIS IN THE MONKEY

Publisher Summary This chapter discusses the two cardiorespiratory patterns of anaphylaxis in a monkey. The clinical manifestations of anaphylaxis in man show a considerable variation. One possible explanation for this may be involvement of different types of antibodies. The chapter presents an investigation that was undertaken to study mechanisms inducing shock in anaphylaxis mediated by two types of antibodies. The first type of anaphylaxis was induced in monkeys possessing a high concentration of specific IgG antibodies, and the second type was induced in monkeys having a high concentration of specific IgE antibodies. The experiments were performed under ketamine hydrochloride anesthesia in spontaneously breathing animals. A redistribution of blood flow to the heart and brain at the expense of flow to other organs occurred during both types of anaphylaxis. An initial redistribution of flow within the left ventricular myocardium resulted in a relative decrease in subendocardial flow.