Effects of phentolamine on hepatic PO2 in endotoxemia.
The effect of phentolamine, an alpha-adrenergic blocker, on hepatic oxygen supply, plasma glucose, and lactate, and survival in fasted male rats administered Echerichia coli endotoxin (25 mg/kg, ip) has been studied. Survival at 24 h was 8% in untreated endotoxic rats, 83% in rats receiving phentolamine (5 mg/kg, ip) and endotoxin, and 100% in phentolamine controls. Measurements during the initial 8 h postendotoxin recorded transiently lower systemic arterial pressure in the phentolamine-endotoxic rats. Arterial PO2 and increases of pH and heart rate were similar in both endotoxic groups. Lactacidemia, present by 4 h in untreated endotoxic rats, did not develop in the phentolamine group and plasma glucose was significantly higher at 8 h (98 +/- 2.5 vs. 77 +/- 5.6 mg%, mean +/- SE). Mean hepatic PO2 at 6 h in phentolamine-endotoxic rats was 9.6 mmHg with 28% of the values below 5 mmHg. By contrast, the mean in untreated endotoxic rats was 1.9 mmHg with 88% of values below 5 mmHg. Phentolamine controls were stable over 8 h; mean hepatic PO2 was 17.7 mmHg. The differences in plasma glucose and lactate suggest protection of hepatic metabolism in phentolamine-treated endotoxic rats by prevention of excessive hepatic hypoxia.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D006339:Heart Rate / Q000187:drug effects; D007773:Lactates / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects
D001786:Blood Glucose; D004731:Endotoxins; D007773:Lactates; D011942:Receptors, Adrenergic, alpha; D010100:Oxygen; D010646:Phentolamine