Summary
The material reviewed, and presented, here lends credence to the concept that the severity or course of the shock syndrome can be evaluated, quantitatively, at a tissue level by assessing RES phagocytic function. In general, the available data indicate that RE cell stimulants can adapt animals (and probably man) to the insults of circulatory shock and trauma; such substances could have important value in pretreating patients scheduled for massive surgery. The fact that a number of biologically active materials with vasotropic, and RE cell depressant, effects appear in the tissues and blood in shock, particularly when the organism becomes refractory to therapy, suggests that the final functional deterioration of the cardiovascular system may be due to the specific action of one or more of these biologically active materials; such a contender is, without doubt, histamine.
Histamine has all the attributes of a typical shock-toxin. Evidence is presented that histamine can be a potent splanchnic (shock target-organ) arteriolar (microcirculatory) dilator even in physiologic (circulating) concentrations. Concentrations of histamine found in plasma of shocked animals and human subjects would produce extremely potent splanchnic vasodilator actions at the microcirculatory level. Evidence is also presented to indicate that microvessels can synthesize and release free, pharmacologically-active histamine.
Endogenous release of histamine (e.g., with compound 48/80) produces dose-dependent and lethal shock-like anaphylactic actions; such release also produces, dose-dependently, RES phagocytic depression. Repeated administration of the histamine releaser, compound 48/80, results in almost a 400% enhancement of RES phagocytic function and cross-tolerance to lethal doses of whole-body trauma. Such results raise the possibility that the RES plays a pivotal role in the circulatory manifestations of compound 48/80 and anaphylactic-type (histamine release) shock syndromes.
Evidence is presented to indicate that H1-receptor antihistamines can ameliorate circulatory shock (and trauma) and prevent RES phagocytic depression, whereas H2-receptor antihistamines do the reverse. Direct in situ microscopy revealed that the former types of histamine receptor blockers prevent tissue ischemia, whereas H2-receptor blockers exacerbate tissue ischemia in circulatory shock. Histamineinduced vasodilatation via H2-receptors may thus be a beneficial effect in circulatory shock and trauma; one must think seriously about the potential value of antihistamines as adjuvant drugs in the treatment of low-flow states and as preoperative medication.
Collectively, the data reviewed herein could be taken as strong support for a pivotal role for the release (and possible synthesis) of free, pharmacologically-active histamine in shock.
Zusammenfassung
Das hier referierte und gezeigte Material bestärkt das Konzept, daß die Schwere oder der Verlauf des Schocksyndroms quantitativ auf der Gewebeebene durch Abschätzung der RES Phagozytosefunktion berechnet werden kann. Im allgemeinen deuten die verfügbaren Daten an, daß RE-Zellstimulantien Tiere (und wahrscheinlich auch Menschen) auf Kreislaufschock und Traumasituationen adaptieren können; solche Substanzen können einen großen Wert in der Vorbehandlung von für große Operationen vorgesehene Patienten haben. Die Tatsache, daß eine Anzahl biologisch aktiver Materialien mit vasotropen und RE-Zell depressiven Wirkungen gerade dann im Gewebe und Blut erscheint, wenn der Organismus zunehmend therapierefraktär wird, läßt vermuten, daß die finale funktionelle Verschlechterung der Kreislaufsituation in der spezifischen Wirkung von einem oder mehreren dieser biologisch aktiven Materialien begründet ist; solch ein Teilhaber ist ohne jeden Zweifel das Histamin.
Histamin hat alle Eigenschaften eines typischen Schocktoxins. Es werden Beweise dafür erbracht, daß Histamin, sogar in physiologischen (zirkulierenden Konzentrationen ein potenter Splanchnikus (Schockzielorgan) arteriolärer (mikorzirkulatorischer) Dilator ist. Die gemessenen Plasmahistaminkonzentrationen von Schocktieren und Menschen würden extrem starke vasodilatatorische Wirkungen im Mikrozirkulationsbereich des Splanchnikusgebietes auslösen. Es wird ebenfalls erwiesen, daß Mikrogefäße freies, pharmakologisch aktives Histamin zu synthetisieren und freizusetzen in der Lage sind.
Endogene Histaminfreisetzung (z.B. mit Verbindung 48/80) führt zu dosisabhängigen und letalen schockähnlichen anaphylaktischen Reaktionen; eine solche Freisetzung führt ebenfalls dosisabhängig zur Einschränkung der RES phagozytären Funktion. Wiederholte Gabe des Histaminfreisetzers 48/80 führt zu einer beinahe 400%-igen Erhöhung der RES phagozytären Funktion und Kreuztoleranz von letalen Dosen von Ganzkörper-Trauma. Solche Ergebnisse lassen es möglich erscheinen, daß das RES eine Schlüsselrolle in der Kreislaufmanifestation durch die Verbindung 48/80 und seines anaphylaktischen Schocksyndroms durch Histaminfreisetzung besitzt.
Es wird gezeigt, daß H1-Rezeptorantagonisten zur Verbesserung des Kreislaufschockgeschehens (und Trauma) führen und dabei die RES Depression verhindert wird, während H2-Rezeptorantagonisten genau das Gegenteil tun. Direkte in situ Miroskopie zeigte, daß H1-Rezeptorblocker Gewebeischämie verhindern, während H2-Rezeptorblocker die Gewebeischämie im Kreislaufschock noch verstärken. Histamininduzierte Vasodilatation durch H2-Rezeptoren ist damit möglicherweise ein Effekt der im Kreislaufschock und Trauma von Vorteil ist. Es muß deshalb über den potentiellen Wert von Antihistaminika als adjuvante Arzneimittel in der Behandlung von „Niedrigflußzuständen“ und als preoperative Medikation sorgfältig nachgedacht werden.
Zusammengefaßt können die hier referierten Daten als starke Unterstützung für eine Schlüsselrolle von freigesetztem (und möglicherweise gebildetem freien pharmakologisch aktivem Histamin bei Schockzuständen angesehen werden.
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Supported by Research Grants H1 18002, HL 18015 and DA 02339 from the U.S.P.H.S.
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Altura, B.M. Reticuloendothelial system function and histamine release in shock and trauma: Relationship to microcirculation. Klin Wochenschr 60, 882–890 (1982). https://doi.org/10.1007/BF01716944
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DOI: https://doi.org/10.1007/BF01716944