CSF, sagittal sinus, and jugular venous pressures during desflurane or isoflurane anesthesia in dogs.

Previous studies to determine whether desflurane increases cerebrospinal fluid (CSF) pressure are inconclusive because none have included all of the following: multiple doses of desflurane, administration for at least several hours, examination at normo- and hypocapnia, a concurrent comparison group, direct measurement of both intra- and extracranial CSF pressures, and measurement of venous pressures that influence CSF pressure. The present study was designed to determine whether CSF pressure increases during 4.0 h desflurane anesthesia using a study design that included the above elements. Catheters were placed in the lateral cerebral ventricle, cisterna magna, sagittal sinus, and jugular vein of 12 dogs anesthetized with thiopental 12 mg.kg-1.h-1 and halothane 0.5 to 0.8%. Catheter pressures were measured, and the CSF-sagittal sinus pressure gradient and slope of the gradient to CSF pressure relationship were determined during control conditions. Then, 6 dogs were anesthetized with desflurane and 6 dogs were anesthetized with isoflurane, and the same values were determined for 1.0 h at each of four experimental conditions: 0.5 and 1.0 minimum alveolar concentration (MAC) during normocapnia (PaCO2 35-39 mm Hg) and 0.5 and 1.0 MAC during hypocapnia (PaCO2 20-24 mm Hg). CSF and sagittal sinus pressures, but not jugular venous pressure, increased with both desflurane and isoflurane. The greater increase of CSF pressure with 4.0 h desflurane (to 40.2 +/- 12.7 cm H2O) than with 4.0 h isoflurane (to 26.2 +/- 11.5 cm H2O) was attributable to an increase of CSF pressure that was greater during 2.0 h desflurane and normocapnia than during 2.0 h isoflurane and normocapnia, and to an increase of CSF pressure during 2.0 h desflurane and hypocapnia that was similar to that during 2.0 h isoflurane and hypocapnia. The greater increase of CSF pressure during desflurane may have resulted, in part, from increased CSF volume as indicated by a positive CSF-sagittal sinus pressure gradient (in contrast, there was little or no CSF-sagittal sinus pressure gradient during isoflurane) and a steeper slope of the gradient to CSF pressure relationship.

The type III phosphodiesterase inhibitor milrinone and type V PDE inhibitor dipyridamole individually and synergistically reduce elevated pulmonary vascular resistance.

The effects of the phosphodiesterase (PDE) inhibitors milrinone and dipyridamole were studied in an in situ perfused rabbit lung model in which the pulmonary vascular resistance (PVR) was elevated by infusion of the thromboxane-A2 mimetic U46619. Dose-response curves for reduction of elevated PVR were generated for each of these drugs. The EC50 for milrinone was approximately 2 microM. The EC50 for dipyridamole was approximately 0.2 microM. In separate experiments, 0.1 microM milrinone was found to reduce elevated PVR by 4.6 +/- 2.4%, 0.06 microM dipyridamole reduced elevated PVR by 8.2 +/- 2.8%, whereas the combination of 0.1 microM milrinone and 0.06 microM dipyridamole reduced elevated PVR by 41.9 +/- 7.3%. In more limited experiments, it was determined that the PDE type V inhibitor zaprinast also caused a synergistic reduction of PVR when used with milrinone. We concluded that both the type III PDE inhibitor milrinone and the type V PDE inhibitors dipyridamole or zaprinast are effectively able to reduce elevated PVR and that the combination of PDE type III and type V inhibitors is synergistic in the ability to reduce elevated PVR. We speculate that type V PDE may play a more important role than type III PDE in the regulation of pulmonary vascular tone. It is proposed that the combination of milrinone and dipyridamole has the potential to be useful in the clinical treatment of elevated PVR.