Pathogenesis of Lethal Shock After Intravenous Staphylococcal Enterotoxin B in Monkeys

Abstract

The pathogenesis of shock in the rhesus monkey given intravenous staphylococcal enterotoxin B (SEB) is not understood. Several cardiovascular changes produced by a highly purified preparation of SEB were studied after administration of doses ranging from 50 to 1,000 μg/kg. Irreversible arterial hypotension was found consistently at the higher doses. Arterial blood pressure and cardiac output declined substantially as shock developed. Total peripheral vascular resistance did not rise at any time, but showed a significant fall during the late stages of shock. Portal and central venous pressures remained essentially unchanged. Venous O 2 content and pO 2 declined gradually throughout the period of toxemia, but arterial O 2 content remained constant until just prior to death, when a slight fall was noted in some monkeys. These changes were consistent with a pooling of blood in the peripheral vascular beds and seemed to resemble cardiovascular responses reported to occur in monkeys during shock due to bacterial endotoxin. Epinephrine, administered in the late stages of shock, caused arterial pressure to increase almost immediately and cardiac output to return to normal about 1 min later. Although life could occasionally be prolonged for several hours by continuous or intermittent epinephrine infusions, this therapy never succeeded in reversing the lethal effects of high doses of SEB.

The Effect of Intravenous Staphylococcal Enterotoxin B Intoxication on Physiological Parameters in Rhesus Macaques As Measured By Telemetry

“…SEB intoxication has been shown to cause a wide spectrum of symptoms, dependent on the route of exposure. The rhesus macaque has been used as a model for inhalational and intravascular SEB intoxication [15][16][17][18][19][20][21][22][23][24][25]. While initial results have been promising, particularly for the inhalational model, the data collected has focused on hematological values, tissue pathology, and clinical signs observed.…”

“…SEB is classified by the Center for Disease Control (CDC) as a select agent under the Federal Select Agent Program, and as such is often used in animal studies for the development of therapeutic countermeasures. SEB has been previously modeled in the rhesus macaque (Macacamulatta) with success for intoxication [15][16][17][18][19][20][21][22] and is the best model for lung pathology following inhalational exposure [23][24][25]. However, not much is known about the physiological parameters in the rhesus macaque model to evaluate the similarities compared to human intoxication.…”

Cardiovascular and Vomiting Responses to a Lethal Intravenous Dose of Staphyloenterotoxin A in Rhesus Monkeys

“…In addition to gastrointestinal disturbances, hypotension, pallor, shock, compensatory tachycardia, and terminal bradycardia were common findings in monkeys given either intravenous SEA or SEB [5,11]. Another common sign shared by monkeys with SEA or SEB toxemia was the gradually decreased blood pressure which persisted until shortly before death [8]. If the shocks induced by SEA and SEB are caused by the same mechanisms, then pulmonary edema [7], severe vasoconstriction, dehydration, and decreases in plasma volume, blood volume, and cardiac output may play significant roles in causing death during SEA enterotoxemia [11,12].…”

“…The lethal physiological responses to intravenous SEB have been studied most extensively in the rhesus monkey [5,6,8,Il,12], but the intravenous effects of highly purified SEA have been reported only in cats [3]. Further, SEA is known to have important immunochemical dissimilarities from SEB [15].…”