Failure of indomethacin to prevent or ameliorate oleic acid pulmonary edema in the dog.

The possibility that prostaglandin synthesis inhibition might favorably inhibit the development of animal adult respiratory distress syndrome models was investigated in two groups of dogs; one group was pretreated with indomethacin 3 mg/kg. Both groups received oleic acid 0.15 mg/kg. Measurements of gas exchange and hemodynamics were performed every hour for 5 hours following embolization. Severe pulmonary edema developed in both groups. The indomethacin pretreated group responded similarly to the control group; there was no difference in the 5 hour course of Pa02 (p = .34), P(A-a)02 (p = .21) or QS/QT (p = .99). Prostaglandin synthesis inhibition did not favorably influence the immediate development of acute respiratory failure following oleic acid.

Pharmacokinetics of naloxone and naltrexone in the dog.

The serum kinetics of 5 mg/kg of i. v. naloxone or naltrexone were studied in each of two groups of five dogs; serum samples were obtained from 2 min to 2 hr after injection. Serum concentrations were determined by radioimmunoassay. Serum levels of both naloxone and naltrexone fell rapidly; serum half-life during the elimination phase was 71.2 +/- 8.9 min (mean +/- S.E.) for naloxone and 85.1 +/- 9.0 min (mean +/- S.E.) for naltrexone. Although human and dog kinetics are similar for naloxone, naltrexone is long-acting in man, but is quickly dissipated in the dog.

Acute and chronic changes in intra- and extracellular potassium and responses to neuromuscular blocking agents.

The effects of acutely induced metabolic and respiratory alkalosis with reduction of serum potassium concentration as well as chronic total body potassium depletion induced by furosemide treatment were evaluated and correlated with alteration of neuromuscular blockade induced by d-tubocurarine, pancuronium, and succinylcholine in 12 mongrel dogs. Acute respiratory and metabolic alkalosis significantly reduced serum potassium by about 26%, while chronic furosemide treatment (1 mg/kg IV daily for 14 +/- 4 days) significantly reduced both serum potassium concentration (4.16 +/- 0.31 to 3.27 +/- 0.14 mEq/L) and skeletal muscle potassium content (80.9 +/- 5.6 to 58.7 +/- 4.1 mEq/kg). Succinylcholine neuromuscular blockages was essentially unchanged by acute respiratory or metabolic alkalosis or by chronic furosemide treatment, except for more rapid onset of blockade when 0.1 mg/kg succinylcholine was administered during metabolic alkalosis. Acute respiratory alkalosis shortened the duration of neuromuscular blockade induced by d-tubocurarine and pancuronium while acute metabolic alkalosis shortened the duration of pancuronium only and had no effect on d-tubocurarine. Chronic furosemide treatment had no effect on either d-tubocurarine or pancuronium neuromuscular blockage. Potassium concentration gradients between the intracellular and the extracellular compartments may be more important than cellular potassium depletion per se in affecting responses to neuromuscular blocking agents such as succinylcholine, d-tubocurarine, or pancuronium. Serum alkalemia and hypokalemia antagonize the duration of the neuromuscular blocking action of d-tubocurarine and pancuronium but not that of succinylcholine.

Effects of anesthetic doses of morphine on renal function in the dog.

Renal effects of anesthetic doses of morphine (2 mg./kg.) administered intravenously (I.V.) were determined in 15 mongrel dogs before and after addition of 50 percent nitrous oxide (N2O). Morphine significantly increased urine osmolarity and decreased urine output, free-water clearance, and arterial blood pressure, but did not affect inulin or para-aminohippurate (PAH) clearances. Addition of N2O did not significantly change arterial blood pressure and inulin clearance but did decrease urine osmolarity and osmolar and PAH clearances. These data demonstrate that, in contrast to man, anesthetic doses of morphine have significant antidiuretic properties in the dog.