Effects of progressively increased doses of theophylline and of S 9795 on hemodynamics, blood gases and lung mechanics in dogs.
We investigated the effects of progressively increased i.v. doses of theophylline and of the newly introduced methylxanthine derivative S 9795 on hemodynamics, blood gases and lung mechanics in 2 groups each of 8 pentobarbital sodium-anesthetized dogs. The maximum plasma levels that were attained were 56.6 +/- 3.4 micrograms/ml (mean +/- S.E.) for theophylline and 12 +/- 1.2 micrograms/ml for S 9795. Theophylline increased heart rate and cardiac output, decreased arterial PO2, increased O2 consumption and did not affect lung mechanics. S 9795 decreased heart rate, increased systemic arterial pressure, O2 consumption (slightly) and pulmonary capillary wedge pressure (the latter only at the highest dose) and decreased lung compliance without change in lung resistance. The evolutions of heart rate, O2 consumption and pulmonary capillary wedge pressure differed significantly after theophylline compared to S 9795. These results show that in dogs, theophylline acts as a positive chronotrope, while S 9795 either has no such effect or acts as a negative chronotrope at high doses. None of the 2 methylxanthines appears to reduce normal bronchomotor tone.
Lejeune
P
P
Laboratory of Cardiovascular and Respiratory Physiology, Erasmus University Hospital, Brussels, Belgium.
Naeije
R
R
D000818:Animals; D001784:Blood Gas Analysis; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology*
D014970:Xanthines; C055633:S 9795; D013806:Theophylline