Studies of Rickettsial Toxins

Summary Intravenous administration of lethal quantities of murine typhus toxin to white rats is followed by a characteristic and reproducible pattern of changes in the meso-appendiceal vascular bed. After a latent period of about ½ hr, the large and small arterioles and precapillaries undergo a constriction that gradually increases in intensity until the animal dies. At the same time, capillary blood flow diminishes progressively finally leaving the capillary bed markedly ischemic. Epinephrine sensitivity of the terminal arterioles and precapillaries does not change throughout the course of the toxemia. Hemoconcentration is generally present terminally. Despite this, systemic arterial blood pressure in the unanesthetized animal remains essentially unchanged until near death. These observations suggest: a) capillary vascular permeability is increased in a remarkably specific manner that leaves unaltered the capacity of terminal arterioles and precapillaries to react to epinephrine or to participate in certain reflex compensatory mechanisms and b) the humoral vasoexcitor mechanism (VEM) usually operative in acute blood loss does not function. The systemic arterial blood pressure in the anesthetized rat falls sharply at about the same time that the visible peripheral arteriolar constriction and slowing of blood flow commence. Unaltered hematocrit values at the time of rapid fall in arterial blood pressure stand as evidence against the occurrence of hemoconcentration at this early stage. These observations strongly suggest that cardiac output, at least in the anesthetized animal, is appreciably diminished early in the course of the toxemia prior to, and initially independent of, a reduction in total blood volume from the loss of plasma into the tissues through excessively permeable vessels. The distinctive pattern of peripheral vascular changes caused by lethal doses of murine typhus toxin in white rats differs in important details from the effects of lethal amounts of Salmonella typhosa endotoxin and from acute blood loss by hemorrhage.