Res. exp. Med. 166, 173 - 181 (1975) ©by

Springer-Verlag 1975

Myocardial Damage during Protracted Anaphylactic Shock in Guinea Pigs M. HAGEDORN, W. BERNAUER und CH. MITTERMAYER Universit~ts-Hautklinik (Prof. Dr. K.W. Kalkoff) Pharmakologisches Institut der Universit~t (Prof. Dr. G. Hertting) und Pathologisches Insitut der Universit~t (Prof. Dr. W. Sandritter) in Freiburg im Breisgau Received June 23, ]975

Summary: In ovalbumin-sensitized, mepyramine-treated guinea pigs protracted anaphylactic shock was elicited by i,v. injection of antigen, Diffuse or focal necrosis of myocardial cells was found in animals which died in protracted shock, as well as perivascular and interstitial edema, The antigen effects could be partially imitated by i.v. infusion of high amounts of adrenaline into nonsensitized guinea pigs, When adrenaline was infused during protracted anaphylactic shock, the catecholamine effects did not add to the histological effects of the antigen. Rather, the morphological alterations in the hearts were reduced, whereas the survival times were not increased, but decreased. The findings are discussed in view of the nature of protracted anaphylactic shock.

Key words: Protracted anaphylactic shock - myocardial cell damage - adrenaline Zus~menfassung: Bei ovalbuminsensibilisierten, mepyraminvorbehandelten Meerschweinchen wurde durch intravenSse Injektion yon Antigen ein protrahierter anaphylaktischer Schock ausgelSst. Bei Tieren, welche im protrahierten Schock verstarben, konnten sowohl diffuse als auch herdfSrmige Herzmuskelzellnekrosen gefunden werden. Ferner waren perivaskulgre und interstitielle Odeme nachweisbar. Die Antigeneffekte bei nicht sensibilisierten Tieren konnten durch intravenSse Infusion hoher Dosen von Adrenalin teilweise imitiert werden. Wurde Adrenalin im Verlaufe des protrahierten Schocks infundiert, so nahm das Ausma~ der Herzmuskelzellnekrosen nicht zu. Die histologischen Ver~nderungen waren eher vermindert, obgleich die Uberlebenszeit nicht verl~ngert sondern verk~rzt war. Die Befunde werden im Hinblick auf die Pathogenese des protrahierten anaphylaktischen Schocks diskutiert.

Schl~sselw~rter: Protrahierter anaphylaktischer Schock - Herzmuskelzellnekrosen - Adrenalin

The protracted anaphylactic shock of guinea pigs is an unresolved problem as to its causes. This type of shock results when the antigen-antibody reaction is delayed by subcutaneous or intraperitoneal administration of the antigen (WILLIAMSON, 1936; STONE, ]959). But it can be observed also after i,v, in-

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M. Hagedorn et al.

jection, when the otherwise acute bronchospastic death is prevented by antihistaminics (WILCOX and SEEGAL, 1942; GREEN, 1953). Animals which died in protracted shock have practically no emphysema of the lungs, but signs which point to circulatory failure. The heart is dilated, and congestion of liver and intestines can be found. Pulmonary and coronary vascular spasms were considered to be causes of the protracted shock (GIERTZ et al., BERNAUER,

1961a, HAHN and

1971). Indeed, in isolated lungs, in heart-lung preparations, and

isolated perfused hearts of guinea pigs the anaphylactic reaction leads to a very marked constriction of these vessels (WILCOX and ANDRUS,

et al.,

1960; GIERTZ et al.,

1938; FEIGEN

1961b, GREEFF and HEEG, 1964; BERNAUER et al.,

1969; HAHN and BERNAUER, 1970; HAHN et al.,

1970). And in guinea pig heart-

lung preparations anaphylaxis provokes a breakdown of cardiac function (HAHN and BERNAUER,

1969).

The purpose of the present study was to get further information about the role of the heart in protracted shock and that with regard to possible morphological alterations. Besides the heart, also the lung, kidney, liver, and adrenals were investigated for an eventual anaphylactic damage. Since in protracted anaphylactic shock very high serum adrenaline concentrations were found (BERNAUER et al.,

J971), adrenaline was infused into nonsensitized as

well as anaphylactic animals and the morphological effects compared with those of antigen alone.

METHODS Guinea pigs of either sex (body weight 200-450 g) were used. Sensitization was performed by i.p. injection of 0.1 ml of a 5% ovalbumin solution in saline (albumen ovi siccum, Merck Comp., Darmstadt), on days I, 3 and 5. Beginning with day 21 the animals were used for anaphylaxis experiments. Sensitized, or nonsensitized animals were anaesthetized with urethane (1.5 g/kg, i.p.). Both jugular veins were isolated and mepyramine maleate (0.1 mg/kg; in I ml/kg,) or saline (I ml/kg) was injected into the left jugular vein. From animals which died in the protracted anaphylactic shock tissue slices from heart, lung, liver, kidneys and adrenals were removed immediately after death. Animals which survived 120 min after eliciting anaphylaxis were sacrificed at this time by opening the thorax. Tissue slices were taken immediately, too. In special groups of nonsensitized, or sensitized guinea pigs, immediately after the ovalbumin injection an infusion of adrenaline hydrochloride (I, or 10 vg/min) into the left jugular vein was started. Animals of identical bodyweights were chosen to keep the adrenaline dosis constant in all groups. The animals were either sacrificed at definite times for histological investigation, or tissue slices were taken from animals which died spontaneously from anaphylaxis or from the adrenaline. All tissue slices were fixed in phosphate buffered formalin (pH 7.O). The following staining procedures have been applied to always 7 paraffin embedded sections: Hematoxylin-Eosin; Goldner trichrome stain; PAS reaction, and Elasti-

Protracted Anaphylactic Shock in Guinea Pigs

175

ca van Gieson. Especially the hearts have been investigated in at least three different slices in serial technique. In addition in four animals a protracted anaphylactic shock was elicited to investigate the cardiac morphology in more detail. The hearts were fixed immediately after death, or intra vitam respecti¢ely, by the following procedure: Heparin (50 E/ml saline) was infused via the aorta into the heart with the aid of an infusion pump (B. Braun, Melsungen) until the venous effluent was free of blood. Then, perfusion with I% glutaraldehyde followed for 15-20 min. Thereafter, the tissue was embedded and cut into s~ices of 1 D thickness. Staining was accomplished with toluidine blue. RESULTS From 20 sensitized guinea pigs which received mepyramine and 5 min later ovalbumin,

16 died in the protracted anaphylactic shock, after 7],6 ± 6,42 min in

the mean. Histological investigation of the hearts (group la of Table I) revealed in 15 out of the 16 guinea pigs diffuse necrosis of the myocardial cells, Focal necrosis and signs of myocytolysis were found in all 16 animals, At the border of those necrotic areas in some preparations accumulations of granulocytes were seen. Furthermore, aggregations of granulocytes were detected within the vessels in all hearts, with the typical "sticking phenomenon", Moreover, perivascular and interstitial edema was found in all hearts, and, less frequently, valvular edema. The cardiac lymphatics were conspicuously dilated (Fig, I).

Fig. I. Diffuse multifocal necrosis in the left ventricle with marked dilatation of the lymphatic vessels (~). (hematoxylin-eosin, magnification x 90)

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