Anaphylactic shock in monkeys passively sensitized with human reaginic serum

Abstract

Mechanisms inducing a low cardiac output (CO) state in IgE-mediated (cytotropic) anaphylactic shock in anesthetized Macaca irus monkeys were studied. 7 monkeys were sensitized by 2 i.v. injections of a human reaginic serum containing a high concentration of IgE antibodies against dog albumin. Anaphylactic shock was elicited 48 h after the last sensitization dose, by an i.v. injection of dog albumin. The severe anaphylactic shock which developed was characterized by an initial phase consisting of increased CO (+16%, mean value, 1 min after challenge), pulmonary hypertension and systemic vasodilatation followed by a phase consisting of decreased CO (-67%), a fall in mean arterial pressure from 113 to 45 mmHg, decreases in left and right arterial pressures (-5.3 and -3.2 mmHg, respectively) and increases in pulmonary vascular (+364%) and total peripheral (+30%) resistances. These changes were recorded 5 min after challenge and the values then remained essentially unaltered during the rest of the 30-min observation period. Pulmonary vascular resistance was only increased by 140% at the end of that period. Myocardial blood flow was maintained during shock at the expense of flow to other organs. However, initially there was a redistribution of blood flow within the left ventricular myocardium, resulting in a relative decrease in subendocardial flow. This finding was not related either to occasional S-T changes in the electrocardiograms or to the level of decreased CO. The oxygen supply to the myocardium was reduced in shock but the reduction was always smaller than the corresponding decrease in heart work. Two additional monkeys sensitized with an IgE fraction from the human serum showed a smaller amount of specific IgG in their serum prior to challenge than the other monkeys. The response to challenge was milder, but resembled the initial vasodilatory reaction in monkeys sensitized with serum. These data on cytotropic anaphylaxis in the monkey show that the main cause of decreased CO and thus of the shock state is a decreased venous return, primarily due to peripheral blood pooling and, to a smaller extent, extravasation of plasma. No appreciable involvement of the heart in the induction of shock was detected.

Pulmonary Vasoconstrictive and Bronchoconstrictive Responses to Anaphylaxis Are Weakened via β2-adrenoceptor Activation by Endogenous Epinephrine in Anesthetized Rats

“…Moreover, in the isolated perfused Brown Norway rat lung, PAP increased only by 1.7-2.2 mmHg. 22 These findings contrast with those of other experimental in vivo models of anaphylactic shock in dogs, 7,8 monkeys, 6 rabbits, 9 and sheep, 5 where PAP increased by 11-16 mmHg after antigen administration. This indicates that the anaphylactic pulmonary vasoconstriction is much weaker in rats than in other mammals.…”

“…Systemic anaphylaxis is sometimes accompanied by pulmonary vasoconstriction and bronchospasm in humans 4 and animals. [5][6][7][8][9] Constriction of the pulmonary vessels and bronchi could increase right heart load, and then augment anaphylactic hypotension. However, it is not well known whether pulmonary vasoconstriction and bronchoconstriction accompany anaphylactic hypotension in in vivo SD rats, although they were reported to occur in the anaphylactic response of isolated perfused rat lung.…”

Definition and classification of the histamine-release response to drugs in anaesthesia and surgery: Studies in the conscious human subject

“…However, this communication illustrates by one intensely studied example with one clinically used histamine releaser (experiments in animals and human subjects for more than /0 years [29-32, 34, 39, 40, 44, 54] that the classical symptoms of anaphylaxis are rare in histamine-release responses in general and only more common ("classical") in grade III reactions. Increasing experience, however, in animals [6,25,42,49,50,60] and in man [61] is forming the suggestion that even this may not be true: Clinical pictures of severe heart attack or arrhythmias may be caused by histaminerelease responses which clearly have to be classified as grade III reactions.…”

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

“…These mechanisms are reviewed elsewhere (Pavek et al 1982;Smedegard et al 1981;Szebeni 2005) and are outside the scope of this report. For example, a mAb infusion reaction in monkeys was demonstrated by Hu1D10, a humanized mAb directed against human leukocyte antigen (HLA)-DR. After dosing, an anaphylactic reaction that included respiratory suppression, increased heart rate, and urticaria occurred in five of the eight treated animals.…”