Endotoxin cardiovascular shock

Heneka, M.T. Loschmann, P.-A. Osswald, H. Polymerized hemoglobin restores cardiovascular and kidney function in endotoxin-induced shock in the rat. J. Clin. Invest. 1997, 99, 47-54. 

Natanson C, Eichenholz PW, Danner RL, Eichacker PQ, Hoffman WD, Kuo GC, Banks SM, MacVittie TJ, Parrillo JE. Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med 1989 169(3) 823-832. 

TNF is a primary mediator of circulatory shock (Tracey et ai, 1986, 1987 for a review see Billiau and Vandekerchove, 1991). Administration of TNF alone or in combination with low (otherwise ineffective) doses of endotoxin, produces effects that, mimic several cardiovascular features of circulatory shock, including hypotension, peripheral vasodilatation, and organ damage (for a review see Billiau and Vandekerchove, 1991). Elevated plasma concentrations of TNF are found in endotoxemia (Beutler et al., 1985 Waage, 1987 Michieeta/., 1988 Feuerstein etal., 1990 Klosterhafen et ai, 1992). In addition, antibodies directed against TNF (Tracey et al., 1987 Mathison etal., 1988 Hinshaw etal., 1990 Silva etal., 1990 Walsh et al., 1992) or agents that inhibit the release of TNF, such as pentoxifylline (Schade, 1990), exert protective effects in animal models of endotoxin shock. 

Thus, there is strong experimental evidence suggesting that (1) TNF and IL-1 are key mediators of endotoxin shock, (2) TNF and IL-1 can induce iNOS in vitro, and (3) iNOS and the resulting enhanced formation of NO contribute to cardiovascular failure in endotoxin shock. 

Although the prevention of the endotoxin-induced circulatory failure with the above agents appears to be an important approach for the therapy of a variety of diseases, it should be stressed that the beneficial effects of these agents—when administered in animal models of circulatory shock after the initiation of endotoxemia—are limited (Tracey etal., 1987 Mathison et al., 1988 Hinshaw et al., 1990 Silva et al., 1990). For example, inhibition of iNOS induction with corticosteroids (Radomski et al., 1990 Knowles et al., 1990b) prevents the cardiovascular failure caused by endotoxin, but does not exert beneficial cardiovascular effects once iNOS induction has occurred (Wright et al., 1992 Paya et al., 1993). 

McKechnie, K., Furman, B.L. and Parratt, J.R. (1985). Metabolic and cardiovascular effects of endotoxin infusion in conscious unrestrained rats Effects of Methylprednisolone and BW755C. Circ. Shock, 15, 205-215... 

Yao T, Xiao YF, Sun XY, Tong HH et al., 1984 Effects of anisodamine on cardiovascular activities in endotoxin-shocked dogs. Chin Med J pp. 871-876... 

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