The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Dec 1984
Porcine systemic and regional organ blood flow during 1.0 and 1.5 minimum alveolar concentrations of sevoflurane anesthesia without and with 50% nitrous oxide.
Effects of sevoflurane anesthesia on organ blood flow were examined in nine healthy isocapnic pigs using 15-mumol diameter radionuclide-labeled microspheres that were injected into the left atrium. Minimum alveolar concentration (MAC) of sevoflurane required to prevent 50% of the pigs from responding by gross purposeful movement to a noxious stimulus was found to be 2.66 +/- 0.20%. Hemodynamic measurements were made on each pig during the following five conditions: awake (control); 1.0 MAC of sevoflurane anesthesia; 2.66% (1.0 MAC) sevoflurane + 50% N2O anesthesia; 1.5 MAC of sevoflurane anesthesia; and 3.99% (1.5 MAC) sevoflurane + 50% N2O anesthesia. ⋯ However, during 3.99% sevoflurane anesthesia, brain-stem blood flow exceeded that at 2.66% sevoflurane anesthesia. Addition of N2O to pre-established concentrations of sevoflurane increased regional brain blood flow but cerebral and brain-stem blood flow exceeded awake value only during 2.66% sevoflurane + 50% N2O anesthesia. Transmural myocardial blood flow decreased in a dose-dependent manner during sevoflurane anesthesia but the subendocardial/subepicardial perfusion ratio remained at control value.(ABSTRACT TRUNCATED AT 250 WORDS)
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J. Pharmacol. Exp. Ther. · Nov 1984
Treatment of ventricular tachyarrhythmias resulting from amitriptyline toxicity in dogs.
This study was designed to analyze the effects of lidocaine and sodium bicarbonate on ventricular arrhythmias resulting from amitriptyline infusion in dogs. Amitriptyline was infused i.v. at 0.5 mg/kg/min for 30 min, followed by 1 mg/kg/min to dogs anesthetized with morphine and alpha-chloralose. When arrhythmia occurred, the infusion rate was reduced by one-third and the effect of various interventions studied. ⋯ Administration of hypertonic sodium chloride in equimolar quantities to sodium bicarbonate failed to affect amitriptyline-induced ventricular arrhythmias significantly, but hyperventilation to a pH similar to that produced by sodium bicarbonate (7.48) significantly reduced the frequency of amitriptyline-induced ventricular ectopy. When amitriptyline was infused into dogs ventilated with various respiratory rates, ventricular arrhythmia resulted in 18 of 18 (100%) dogs with pH less than 7.42, 2 of 4 (50%) dogs with pH between 7.48 and 7.51 and 0 of 8 (0%) dogs with a pH between 7.59 and 7.65 (P less than or equal to .001). These results suggest that sodium bicarbonate is effective treatment for amitriptyline-induced cardiac arrhythmias with beneficial effects largely due to alkalinization.(ABSTRACT TRUNCATED AT 250 WORDS)
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J. Pharmacol. Exp. Ther. · Aug 1984
Roles of mu, delta and kappa opioid receptors in spinal and supraspinal mediation of gastrointestinal transit effects and hot-plate analgesia in the mouse.
The opioid receptors involved in the mediation of thermal analgesia (55 degrees C hot-plate) and inhibition of gastrointestinal transit at the spinal and supraspinal levels were studied in unanesthetized mice. Five receptor-selective compounds were evaluated for effectiveness in eliciting analgesia and inhibiting transit after both i.c.v. and intrathecal administration; these included the proposed mu agonist, [D-Ala2, N-methyl-Phe4, Gly5-ol]enkephalin (DAGO), the proposed delta agonists, [D-Pen2, L-Pen5]enkephalin (DPLPE), [D-Pen2, D-Pen5]enkephalin (DPDPE) (conformationally constrained delta selective enkephalin analogs) and [D-Thr2, Thr6, Leu5]enkephalin (DTTLE), and the proposed kappa agonist, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate (U-50,488H), as well as the nonselective mu-acting agonist, morphine. ⋯ Similarly, all the compounds produced analgesic responses after intrathecal administration, with the rank order of potency by this route being DTTLE greater than morphine greater than DAGO greater than DPLPE greater than DPDPE greater than U-50,488H, and all compounds (except U-50,488H) had durations of action of up to 20 to 40 min. These agonists also inhibited gastrointestinal transit after intrathecal administration, with a rank order of potency of DAGO greater than DTTLE greater than DPLPE greater than morphine greater than DPDPE greater than U-50,488H.(ABSTRACT TRUNCATED AT 250 WORDS)
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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)