Effects of mercaptoethylguanidine during long-term hyperdynamic porcine endotoxemia

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Introduction

Excess NO production due to iNOS activation and cellular toxicity resulting from peroxynitrite (ONOO^-) may contribute to organ dysfunction in septic shock. Therefore, we studied the effect of the combined ONOO^-scavenger and selective iNOS-inhibitor mercaptoethylguanidine (MEG) [1] on hepato-splanchnic hemodynamics and energy metabolism during long-term hyperdynamic porcine endotoxemia [2].

Methods

12 h after starting continuous intravenous endotoxin, pigs received either no drug (CNT; n=9) or 3 mg/kg/h MEG (n=7). Hydroxyethyl starch was infused to maintain a sustained increase in cardiac output [2]. Before, as well as 12, 18, and 24 h after, the start of LPS we assessed expired NO formation (chemiluminescence), systemic (CO) and liver (Doppler ultrasound flow probes) blood flow, arterial-ileal mucosal PCO₂-gap (fiberoptic sensor), portal (pv) and hepatic venous (hv) lactate/pyruvate (L/P) ratios and hepatic lactate clearance.

Results

See Table.

Conclusion

MEG allowed for hemodynamic stabilization due to blunting of the progressive endotoxin-induced fall in MAP while maintaining CO but did not influence the parameters of hepato-splanchnic energy metabolism. Ongoing oxidative stress resulting from inadequate dosage of the compound may account for this result [3].

Table 1