Bolus administration of 5 mg epinephrine as a treatment of last resort for cardiac arrest.

There is some evidence that the dose of epinephrine currently recommended for resuscitation is low. This study examines the effect of bolus administration of 5 mg of epinephrine when given as an agent of last resort for cardiac arrest. The experimental design called for the administration of high-dose epinephrine at the point where resuscitative efforts would have ordinarily been stopped. Resuscitation was then continued for a minimum of five minutes so that any changes in rhythm or return of spontaneous circulation could be noted. Eighty-five consecutive patients undergoing resuscitation in our Emergency Department were enrolled in this study. Twenty-eight (33 percent) exhibited a change in cardiac rhythm. Of these 28 patients, seven (8 percent) developed pulses. Of these seven patients, four expired in the Emergency Department, one survived to admission but expired two days later, and two patients survived to discharge. We conclude that bolus administration of 5 mg of epinephrine may be useful in treating cardiac arrest refractory to conventional therapy.

Adrenocortical hormones and lactation: metabolism of 3H-corticosterone and 3H-aldosterone by rat mammary gland minces and by the nuclear fraction of the homogenates.

3H-Corticosterone undergoes extensive metabolism on incubation with mammary acini and minced mammary glands from lactating rats; 3H-corticosterone-21-oleate was the major radiometabolite formed. In a similar study with 3H-aldosterone, 3H-aldosterone-21-oleate was one of the two major radiometabolites formed. In the present study, an enzyme system highly active in the biosynthesis of 21-acyl-3H-corticosterone was demonstrated to be present chiefly in the nuclear fraction of mammary gland homogenates. The enzyme system comprises: a fatty acid thiokinase (or fatty acyl-CoA synthetase); a fatty acyl transferase. The methods entailed incubation of 3H-corticosterone with the nuclear fraction in the presence and absence of: the cofactors, CoA, ATP, and Mg2+; oleoyl-CoA and other fatty acyl-CoA donors. The results of the present investigation support the view that the major cellular site for the acylation of adrenocortical hormones is the nucleus. It has been suggested that the acylation serves to modulate the biological action of the hormones on the mammary glands by interaction with the glucocorticoid receptor.

In vitro metabolism of adrenocortical hormones by mammary glands of lactating rats. A comparative study.

A comparative study was made of the metabolism of tritium-labeled corticosterone, cortisol and aldosterone on incubation with minced mammary glands of lactating rats. The yield of total nonpolar (acylated) radiometabolites was highest for [3H]corticosterone, lowest for [3H]cortisol and intermediate for [3H]aldosterone. Unlike [3H]corticosterone, [3H]aldosterone yielded two 21-acyl derivatives (Metabolites I and II) in comparable amounts. Metabolite I (39%) was identified as [3H]aldosterone 21-oleate by isotope dilution analysis. Metabolite II (54%) could not be identified: it is intermediate in polarity between corticosterone 21-oleate and the less polar, corticosterone 21-stearate, and is distinctly less polar than the 21-palmityl, linoleoyl (and presumably also less polar than the arachidonyl) derivatives of aldosterone. The [3H]cortisol metabolites were not further investigated.

In vitro metabolism of [3H] corticosterone by mammary glands from lactating rats. Isolation and identification of 21-acyl[3H]corticosterone.

[3H] Corticosterone undergoes extensive 21-acylation on incubation with minced mammary glands from lactating rats. A purified 21-acyl [3H] corticosterone fraction was obtained by subjecting extracts of the incubated tissues to Sephadex LH-20 column chromatography followed by partitioning between n-heptane/methanol. The methanol extracts were chromatographed consecutively on columns of silica gel and C18-silanized (reverse-phase) silica gel. The radioactive product was methoximated and re-chromatographed on the reverse-phase column. Mass spectral analysis of the 21-acyl [3H] corticosterone 3,20-dimethoxime and synthetic corticosterone 21-oleate 3,20-dimethoxime suggested identity. Confirmation of the precise nature of the 21-acyl moiety was obtained by isotope dilution analysis of the underivatized radiometabolite with corticosterone 21-oleate. The composition of the 21-acyl [3H] corticosterone fraction (i.e. before extensive purification) was ascertained by isotope dilution analysis with various corticosterone esters. It appears that [3H] corticosterone 21-oleate is a major component of this fraction, representing 80% of the radioactivity; [3H] corticosterone 21-linoleate is a minor component, i.e. 8.6%. [3H] Corticosterone 21-palmitate, [3H] corticosterone 21-arachidonate, and [3H] corticosterone 21-stearate, if indeed present, constitute considerably less than 14, 6, and 2%, respectively, of the radiometabolite fraction. It is suggested that bioacylation of corticosterone serves to modulate the biological action of the glucocorticoid hormone on the mammary glands during lactation.