Peripheral Macro- and Microcirculation

Abstract

The association of profound systemic hypotension with the presence of gram-negative Escherichia coli endotoxin in the blood of mammals has been recognized for more than 35 years (Gilbert 1960; Weil et al. 1956). As early as 1943 Homer Smith reported that sublethal concentrations of bacterial pyrogens in humans produce a delayed peripheral vasodilation in the kidney and rise in cardiac output. Since this early report of Smith many investigators have confirmed that this endotoxin-induced systemic hypotension is linked to an inappropriate decrease in total peripheral vascular resistance (Abel and Beck 1988; Bond 1983; Breslow et al. 1987; Nelson et al. 1991; Rackow et al. 1988). Hinshaw described the occurrence of both hyper-dynamic (high cardiac output and low resistance) and hypodynamic (low cardiac output and high resistance) endotoxic/septic shock (Hinshaw 1985). He suggested that the initial response to endotoxin/sepsis was hyperdynamic and that the patient had a good chance of survival if the condition did not progress into a hypodynamic state. In spite of intensive nursing care, patients who do progress to the hypodynamic state of septic shock have a mortality rate as high as 65% (Shubin et al. 1965). This high mortality figure has not changed significantly over the past 35 years (Rackow et al. 1988; Parrillo 1989). Consequently, the severe loss of peripheral vascular tone during endotoxemia represents a prelude to a major clinical problem that has not yet been solved.