The manipulation of stress gene expression by
heavy metals provides protection against the lethal effects of
endotoxemia in murine models of
septic shock. These findings suggest that the increased resistance to
endotoxin in vivo after
stress protein induction could be explained by an attenuation of hemodynamic alterations and an altered pattern of inflammatory mediator release. Therefore, we measured main hemodynamic variables such as systemic and pulmonary artery pressure, cardiac output, heart rate, central venous pressure, and pulmonary artery wedge pressure, as well as the time-course of thromboxane-B2,
6-keto-PGF1 alpha, and
interleukin 6 formation with and without induction of the stress response in an established porcine model of recurrent
endotoxemia (Circ
Shock 35:237-244, 1991). Induction of the stress response was carried out by a pretreatment with Zn2+ (25 mg/kg
zinc-bis-(DL-hydrogenaspartate) = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to
lipopolysaccharide (LPS) infusion induced an increased
heat shock protein 70 (HSP70) expression in the lungs, liver, and kidneys and significantly increased plasma levels of
interleukin 6,
6-keto-PGF1 alpha, and thromboxane-B2, compared with untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators compared with the untreated group. Hemodynamic data presented significantly decreased peak pulmonary artery pressure and pulmonary vascular resistance index values, significantly increased systemic artery pressure and systemic vascular resistance index values, and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of HSP70 by Zn2+ attenuates the liberation of inflammatory mediators, as well as the course of hemodynamic variables due to LPS.