Potentiated cardiodepressant effect of serum by endotoxin in adrenalectomized rats

We have previously shown that in intact rats (IT) a sublethal and nonhypotensive dose (2 mg/kg IV) of Escherichia coli endotoxin was able to induce the early and sustained release of a lipid-soluble cardiodepressant factor, decreasing contractility of cultured rat heart cells by about 35%. As a humoral mediation may also be envisaged in cardiac dysfunction observed by other investigators in adrenal insufficiency, this study was designed to assess serum cardiodepressant effects of endotoxin in 6-10-day, saline-maintained, adrenalectomized rats (ADX). In ADX 2 mg/kg endotoxin caused severe hypotension and 100% lethality within the first 90 min. To obtain in ADX a depressant effect of serum on cultured heart cells fairly similar to that observed in IT, it was necessary to reduce the endotoxin dose by about 200 times (0.01 mg/kg). The latter proved sublethal and nonhypotensive in ADX and was without depressant effect of serum in IT. Serum from ADX (no endotoxin) induced a slight but significant decrease by about 9% in cultured heart cell contractility when compared to serum from IT or sham-operated controls. These data show that adrenalectomy confers a cardiodepressant effect on rat serum and potentiates the release of endotoxin-induced cardiodepressant substance(s) without relation to systemic hypotension.