Immediate Effects of Intravenous Endotoxin on Serotonin Concentrations and Blood Platelets

Abstract

Adult mongrel dogs were given a lethal dose of E. Coli endotoxin by rapid intravenous injection. Total serotonin levels in the serum fell rapidly, with the concentration in the portal vein and pulmonary artery significantly exceeding that in the femoral artery within the first minute after injection. Small rises in plasma serotonin were found in some of the animals. These changes were coincident with a sharp fall in the number of circulating platelets, with striking changes in platelet morphology, and with the initial fall in blood pressure.T HE in vivo administration'of gram negative bacterial endotoxins is associated with certain characteristic manifestations. These include leukopenia, thrombocytopenia, and profound vasomotor disturbances, terminating in shock. 1 In the dog spasm of the small hepatic veins occurs, followed promptly by a rise in the portal venous pressure, with pooling of blood in the liver and intestine, and a subsequent reduction in cardiac output. 2 Changes similar to those produced by endotoxin are also seen after injection of over 70 substances, including glycogen, 3 and bear a remarkable resemblance to the phenomena seen in anaphylaxis.Recent work has shown that serotonin and histamine are released from platelets by antigen antibody reactions, 4 as well as by glycogen, 5 in the rabbit. A histamine like substance also has been identified in dog plasma after endotoxin. 3 Observations by Gordon and Lipton, 6 and by Gilbert 7 have suggested indirectly that serotonin might play a role in endotoxin shock. Because of these findings this work was undertaken to assess the direct effects of intravenously injected endotoxin on serotonin concentrations and on platelets. MethodsMongrel dogs, weighing between 18 and 30 Kg., were lightly anesthetized with thiopental sodium. In 9 dogs the chest was entered through the bed of the left fourth rib. A Starling pump was used to give positive pressure respiration. The lung was retracted and the pericardium opened over the pulmonary artery and outflow tract. The pulmonary artery was secured by means of a 3-0 purse string suture. The arterial wall was incised 1 to 2 cm. above the pulmonary valve, and a salino filled no. 280 polyethylene eannula was inserted into the pulmonai-y artery to record pressure changes. By means of a concentrically fitting cuff the catheter was firmly secured in the desired position. In a similar fashion another catheter, for sampling, was placed in the pulmonary outflowtract, extending through the valves.A chest tube was placed in position to catch dependent drainage, the catheters were brought out between the interlobar fissure to separate stab wounds, and the chest closed. In a second group of 9 dogs the pancreatieoduodenal vein was cannulated, and the catheter was extended into the portal vein. In all dogs bilateral femoral artery cannulation was done, and an additional eannula was placed in the inferior vena cava, via the common femoral vein.Purified E.

Cardiopulmonary Consequences of Pyrogen-Induced Hyperpyrexia in Man*

“…Since those wedge pressures obtained showed no change from base-line levels, it appears that the pulmonary arterioles, unlike those in the skin, the kidneys (4), and the splanchnic bed (22), do not dilate during the flush phase of the pyrogenic reaction. Although our data do not define the mechanism responsible for differences in systemic and pulmonary vascular behavior, the possible role of serotonin release during the pyrogen reaction merits consideration (11,27). Our studies in man contrast with Kuida's demonstration of marked postcapillary pulmonary hypertension in animals (17).…”

Hemodynamic effects of isoproterenol in canine endotoxin shock

“…3). (12,18,(27)(28)(29)(30)(31)(32)(33)(34)(35). In the canine there is a temporary improvement and recovery of the arterial blood pressure after the initial hypotension immediately following endotoxin.…”

Prostacyclin Reversal of Lethal Endotoxemia in Dogs

“…Endotoxemia is associated with thrombocytopenia, leukopenia (1)(2)(3) and the appearance of platelet and leukocyte aggregates in the microvasculature, particularly of the lungs (4-6). These hematologic events are thought to underlie the hemodynamic alterations of endotoxemia that is pulmonary hypertension, low cardiac output, and systemic hypotension.…”