Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat

Effects of the dual endothelin receptor antagonist tezosentan and hypertonic saline/dextran on porcine endotoxin shock

“…Earlier experiences from mixed endothelin receptor antagonism in rat endotoxin models have shown contradictory effects on early survival (Ruetten et al 1996, Ishimaru et al 2001. Conclusions regarding survival should however be made cautiously, as the groups are small.…”

“…In experimental endotoxaemia, dual endothelin receptor antagonists, including bosentan, have improved haemodynamics with increased cardiac index (Oldner et al 1998, Ishimaru et al 2001, attenuated pulmonary hypertension and reduced lung injury (Wanecek et al 1997), as well as improved regional perfusion in the splanchnic region (Oldner et al 1998). So far, the results with non-selective endothelin receptor antagonism and its effects on perfusion pressure have been contradictory (Gardiner et al 1995, Ruetten et al 1996, Oldner et al 1998, Ishimaru et al 2001, Kuklin et al 2004). The few reports on tezosentan in sepsis and endotoxaemia suggest positive effects on cardiac performance (Chin et al 2002, Kuklin et al 2004, lung injury (Kuklin et al 2004, 2005a, renal function (Chin et al 2002) and hepatic injury (Urbanowicz et al 2004).…”

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“…Restoration of splanchnic oxygen delivery in response to bosentan treatment was not associated with an increase in oxygen consumption, suggesting that oxygen consumption was not dependent on oxygen delivery in the gut. However, that study contrasts with others conducted over longer periods of time in that, although splanchnic perfusion per se was not investigated, endothelin antagonists exacerbated endotoxic mediated hypotension [165] and increased mortality [166]. As illustrated by quantative assessments of NO and vasopressin during prolonged exposure to endotoxin or bacteria, cellular function may be profoundly altered, thereby producing a markedly different, and therefore incomparable, picture to the early response.…”

The Influence of Endotoxemia on the Pharmacokinetics and the Electroencephalographic Effect of Propofol in the Rat

“…The degree of metabolic acidosis was also assessed by measuring base excess because this was shown to be a useful marker of the severity of insult 14. Metabolic acidosis observed during endotoxemia is attributable to increased lactate production reflecting tissue hypoxia 15,16. Changes of pH and blood gas values observed during our experiments are similar to those described by others 14,15,17,18.…”