Untersuchungen über Zahl und Funktion der Thrombozyten beim experimentellen Endotoxin-schock des Kaninchens

Abstract

Introduction: During the early phase of shock the blood pressure is decreased due to increased resistance in the terminal vascular system and diminished return of blood to the heart. The late phase is characterized by disseminated intravascular coagulation. The present studies were performed in order to answer the following questions: (1) Does intravascular aggregation of platelets during endotoxin shock depend on the activation of the plasma coagulation system as a first step? (2) May thrombocytopenia or platelet aggregation in the course of endotoxin shock be inhibited by acetyl salicylic acid? (3) Which relations exist between lowering of blood pressure and decrease in the number of platelets? Material and Methods: Blood coagulation was inhibited in 12 rabbits by heparin (20 mg/kg intravenously). Endotoxin was administered to 10 rabbits (100μg/kg/hr). 5 of these rabbits had received acetyl salicylic acid (ASS) 50 mg/kg i. v. 18 hrs prior to endotoxin infusion. 2 animals were used as controls and received an infusion of saline instead of endotoxin. The following investigations were carried out: estimation of blood pressure, platelet count, platelet aggregation and adhesiveness; in vitro effect of endotoxin upon platelet aggregation in plasma rich in platelets. In addition, liver, heart, lungs, kidneys, spleen and adrenals of all animals were submitted to microscopic investigation for the presence of microthrombi. Results: (1) Systolic and diastolic blood pressure were lowered in both shock groups with and without previous administration of ASS. The decrease of blood pressure was less pronounced in the animals treated with ASS. However, no significant difference could be established. (2) The average platelet count was 37% in the shock group without ASS as compared to 62% in the shock group after previous administration of ASS. The difference proved to be statistically significant. (3) Platelet aggregation was less pronounced after administration of ASS than in the shock group without ASS. Platelet adhesion was characterized by large differences in both the shock groups with and those without administration of ASS. (4) Endotoxin did not produce platelet aggregation in vitro. (5) Microthrombosis was present in only 2 animals of the shock group without previous administration of ASS. Discussion: The results suggest that during endotoxin shock platelet decrease and platelet aggregation precede the activation of the plasma coagulation system. The coagulation system of the blood plasma may be activated by substances delivered by the platelets. However, platelet aggregation appears to be insufficient to explain the reduced return of blood to the heart. Since endotoxin does not produce platelet aggregation in vitro, other factors must be responsible for platelet aggregation in vivo. Probably endothelial damage is one of these factors. Obviously, ASS inhibits platelet aggregation and platelet decrease. The relations between platelet number and blood pressure in endotoxin shock remain obscure since both parameters behave differently under the influence of endotoxin and ASS. Blood pressure and platelet count decrease, but the differences between the groups with and without ASS are statistically significant only with regard to the number of platelets. This question may be settled only by further investigations.