The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Jul 1984
Efficacy and mechanism of action of sodium bicarbonate in the treatment of desipramine toxicity in rats.
Alkalinization of the blood by administration of sodium bicarbonate or hyperventilation is widely recommended for treatment of cardiac toxicity due to tricyclic antidepressant overdose, yet its efficacy and mechanism of action are poorly defined. We studied the effects and possible mechanism of action of 1 M NaHCO3 on desipramine (DMI) toxicity in anesthetized, paralyzed rats. Administration of DMI (45 mg/kg i.p.) produced a mean increase in QRS duration of 142% and a mean decrease in mean arterial pressure of 46%. ⋯ Acidosis produced by ventilation with 10% CO2 exacerbated QRS prolongation due to DMI. In acidotic animals, NaHCO3 and NaCl were equally effective in reversing QRS prolongation and hypotension. Correction of respiratory acidosis by discontinuation of inhaled CO2 did not improve QRS duration or mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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J. Pharmacol. Exp. Ther. · Jul 1984
Cardiac autonomic receptors: effect of long-term experimental diabetes.
The present study was undertaken to study the effects of long-term streptozotocin-induced diabetes on ventricular autonomic receptors. Left ventricle and lungs were removed from animals sacrificed either 3 or 6 months after streptozotocin administration (65 mg/kg). Diabetic rats were significantly smaller and had elevated serum glucose and reduced serum insulin values as compared with their age-matched controls. ⋯ As in the 3-month study, the KD values were not affected by the induction of diabetes in any of the receptor systems studied. Inhibition (competition) studies performed in ventricular membranes from the 6-month study demonstrated inhibitory constants (Ki) consistent with labeling alpha-1, beta and muscarinic receptors. Ki values were similar in control and diabetic tissues with one exception: ventricular alpha-1 receptors were found to have a higher affinity for phenylephrine in the diabetic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)