Timing of endothelin and nitric oxide inhibition is crucial for survival in septic shock. BJS 2000; 87: 937-937.
Published: 6th December 2002
Authors: A. B. Iskit, M. O. Guc
The effect of endothelin and nitric oxide inhibition on survival from septic shock was investigated in mice, with particular emphasis on the timing of the administration of their blockers after an endotoxin (lipopolysaccharide; LPS) challenge.
Male Swiss albino mice (20–40 g) received LPS (Escherichia coli 055: B5; 60 mg kg−1 intraperitoneally) followed by intraperitoneal injection of the endothelin receptor antagonist bosentan 30 mg kg−1, either 2 or 12 h after LPS, alone or in addition to intraperitoneal nitric oxide synthase blockers
At 24 h, the survival rate was 10 per cent in controls, but 30 per cent (P not significant) and 70 per cent (P < 0·05) in animals that received bosentan only at 2 and 12 h respectively, indicating a relatively ‘late’ involvement of endothelin. In contrast, these values were 70 per cent (P < 0·05) and 80 per cent (P < 0·05) at 12 h for L‐NAME and
Nitric oxide plays a significantly deleterious role during the early phases of septic shock, in contrast to a relatively late involvement of endothelin peptides. This should be taken into consideration when devising treatment strategies. © 2000 British Journal of Surgery Society LtdFull text