THE INFLUENCE OF HEAT-SHOCK-PROTEIN-70 INDUCTION ON HEMODYNAMIC VARIABLES IN A PORCINE MODEL OF RECURRENT ENDOTOXEMIA

The manipulation of stress gene expression by heavy metals provides pr otection 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 b y 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 out put, heart rate, central venous pressure, and pulmonary artery wedge p ressure, as well as the time-course of thromboxane-B-2, 6-keto-PGF(1 a lpha), and interleukin 6 formation with and without induction of the s tress response in an established porcine model of recurrent endotoxemi a (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-hydroge naspartate) = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolys accharide (LPS) infusion induced an increased heat shock protein 70 (H SP70) expression in the lungs, liver, and kidneys and significantly in creased plasma levels of interleukin 6, 6-keto-PGF(1 alpha), and throm boxane-B-2, compared with untreated controls. After LPS infusion, howe ver, pretreated animals showed significantly decreased peak plasma lev els of all mediators compared with the untreated group. Hemodynamic da ta presented significantly decreased peak pulmonary artery pressure an d pulmonary vascular resistance index values, significantly increased systemic artery pressure and systemic vascular resistance index values , and significantly altered hypodynamic/hyperdynamic cardiac output le vels in the pretreated group. In conclusion, the data show that the in duction of HSP70 by Zn2+ attenuates the liberation of inflammatory med iators, as well as the course of hemodynamic variables due to LPS.