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M Halonen

Publications and source records attributed to M Halonen.

98 records · Page 6Linked to original sources

IgE-induced respiratory and circulatory changes during systemic anaphylaxis in the rabbit.

We studied systemic anaphylaxis induced by the administration of 200 mug of horseradish peroxidase into 11 anesthetized rabbits known to be producing anti-horseradish peroxidase antibodies only of the IgE class. Ventilatory changes included a transient, abrupt decrease in breathing frequency followed by increased minute ventilation; lung mechanical changes included decreased dynamic lung compliance and increased total pulmonary resistance; cardiovascular changes included pulmonary hypertension, systemic hypotension, and, frequently, a transient bradycardia. Recovery from these physiologic changes took place within 60 min. After recovery, the administration of 2 mg of horseradish peroxidase into 6 of the rabbits induced a second reaction indistinguishable from the first with respect to ventilatory and circulatory alterations; however, lung mechanical changes were less prominent. No histologic evidence of pulmonary edema or intraluminal plugging of the pulmonary edema or intraluminal plugging of the pulmonary circulation was observed by light microscopy. Although the first anaphylactic reaction was accompanied by disappearance of stainable basophils from the circulating blood, the second reaction occurred despite the absence of circulating basophils. These studies characterize further the effects of antigen challenge in rabbits producing detectable concentrations of IgE, but not other classes of antibody to the antigen.

Airway Resistance↗

Intravascular effects of IgE antibody upon basophils,, neutrophils, platelets and blood coagulation in the rabbit.

Rabbits synthesizing only IgE antibody to BSA were challenged intravenously with 50 mg BSA and the associated blood cell and coagulation alterations were examined. Basophils decreased by 90% within 1 min of challenge. This was followed by a 70% decrease in neutrophils and a 50% decrease in platelets by 15 min. These changes were found to be highly significant when compared to control unimmunized rabbits similarly challenged. By 60 min, the neutrophils and platelets in the experimental rabbits had returned to 50 and 80% of their prechallenge levels respectively, but no basophils were demonstrable by toluidine blue staining. Lymphocyte counts in the experimental rabbits did not differ from controls at 0, 1, 15, or 60 min after challenge. Blood coagulation alterations also occurred after BSA challenge in the rabbits synthesizing IgE. A significant shortening of the whole blood clotting time in plastic tubes at 25 degrees C occurred in blood samples taken at 30 sec after antigen challenge. Similarly, in vitro addition of BSA to blood samples taken prior to challenge significantly shortened the whole blood clotting time. In addition, significant prolongation of whole blood clotting times was observed in blood obtained 60 min after challenge, but only among the rabbits positive for systemic anaphylaxis. This in vivo study corroborated the known in vitro effects of IgE upon the rabbit blood basophil and platelet. In addition, the results indicate that the intravascular interaction of antigen with specific IgE antibody induced neutrophil and blood coagulation alterations.

Animals↗

IgE-induced blood coagulation alterations in the rabbit: consumption of coagulation factors XII, XI, and IX in vivo.

Intravenous administration of BSA into 3-month-old rabbits producing detectable anti-BSA antibody only of the IgE class of immunoglobulin induced a variety of intravascular blood coagulation alterations observed in the plasma 15 min after antigen challenge included: a) the intravascular consumption of intrinsic blood coagulation factors XII, XI, and IX and possibly the reduction in clottable fibrinogen; b) a significant prolongation of the activated partial thromboplastin time but not the prothrombin time; and c) the production of an inhibitor affecting the last stage of blood coagulation. The observed blood coagulation alterations were not caused by the manipulative procedures utilized, the presence of anti-BSA, IgG or IgM antibody, histamine-induced alterations in the vascular endothelium or the development of hypotensive shock. It is proposed that specific IgE antibody can induce directly or indirectly the activation of intrinsic blood coagulation in vivo.

Aminocaproates↗

Airway cholinergic responsiveness in rabbits in relation to antigen sensitization and challenge.

The development of bronchial hyperresponsiveness to cholinergic agents in relation to antigen sensitization and repeated antigen challenge was investigated in a rabbit model. Rabbits immunized to produce preferentially specific IgE antibodies had a modest enhancement of their bronchoconstrictive response (measured as an increase in pulmonary resistance) to aerosolized methacholine compared to sham-immunized and unimmunized controls. A further enhancement was observed subsequent to a series of seven antigen challenges given transtracheally, such that the geometric mean dose of methacholine required to increase pulmonary resistance by 100% (PD100 RL) was 89 cumulative breath units (CBU) compared to 372 CBU for sham-immunized controls and 871 CBU for unimmunized controls (p less than 0.05 for ANOVA). Although methacholine also decreased dynamic compliance, the changes were not different among the three groups. Isolated intrapulmonary bronchi from the three groups did not differ in log concentration of methacholine yielding a half-maximal contraction (log EC50). The range of EC50 values was 15-fold compared to a 90-fold range of PD100 RL. In vivo cholinergic responsiveness of the pupillary muscle did not correlate with bronchial responsiveness. Thus, pulmonary antigen challenge of IgE-producing rabbits produced a marked increase in bronchial responsiveness which did not correlate with in-vitro bronchial responsiveness or with in vivo pupillary responsiveness.

Animals↗