Azepexole, a potent alpha 2-agonist with anaesthetic effects, does not affect cerebral energy consumption in dogs given isoflurane.

The effects of the alpha 2-agonist azepexole on the cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) were studied by a sagittal sinus outflow technique in dogs. Azepexole, 1 mg kg-1 (reported to decrease the anaesthetic requirement for isoflurane by almost 90%), caused no change in CMRO2 when given during 1.4% isoflurane anaesthesia. CBF was reduced by 26%. When the concentration of isoflurane was reduced to 0.2%, CMRO2 increased by 26% as would have been expected for the change in isoflurane concentration alone. Concomitantly CBF increased to a level not significantly different from control. Azepexole might be a useful adjunct to inhalational anaesthetics, and combined with a low dose of isoflurane it should be an excellent background anaesthetic when studying the effect of other drugs on CMRO2 in dogs as the combination seems to have little effect on the CMRO2.

Cerebral effects of nitrous oxide when added to low and high concentrations of isoflurane in the dog.

The purpose of this canine study was to examine the cerebral vascular and metabolic effects of adding nitrous oxide to isoflurane from 1.4% expired (1 MAC) up to a concentration giving an isoelectric electroencephalogram (EEG). Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) were determined using a sagittal sinus outflow technique. At 1.4% expired isoflurane, 70% nitrous oxide increased CBF but had no effect on CMRO2. At 3.1% expired isoflurane, 70% nitrous oxide had no effect on either CBF or CMRO2. The latter concentration of isoflurane rendered the EEG isoelectric, but when nitrous oxide was added, EEG activity reappeared. To again produce an isoelectric EEG required an increase in the isoflurane concentration to 3.5% +/- 0.2% (with no further effect on CMRO2). The authors also found that at 1.4% isoflurane, 0.9 micrograms.kg-1.min-1 of angiotensin significantly decreased CMRO2 without any effect on CBF. It is concluded that nitrous oxide, when added to isoflurane concentrations ranging from 1.4% to 3.5% in the dog, increases CBF at the low but not the high isoflurane concentrations although it has no effect on CMRO2.

Partial reversal of the cerebral effects of isoflurane in the dog by theophylline.

The cerebral effects of adding theophylline to 1.4% isoflurane anaesthesia were studied in five dogs by a sagittal sinus outflow technique with direct measurement of the cerebral blood flow (CBF) and calculation of the cerebral metabolic rate for oxygen (CMRo2). Three 3 mg.kg-1 doses of theophylline were given with intervals of 10 min. Five min after the second and third dose, when the mean theophylline plasma concentration was 41 and 65 mumols.1(-1), respectively, CMRo2 had increased significantly with a mean value varying between 15% and 13%, and the EEG had changed from a sleep pattern to a more awake pattern in the four dogs with evaluable recordings. There were no significant changes in CBF or mean arterial blood pressure (MABP). It is concluded that the adenosine receptor antagonist theophylline in this study partially reversed the cerebral effects of isoflurane.

Effect of dexmedetomidine, a selective and potent alpha 2-agonist, on cerebral blood flow and oxygen consumption during halothane anesthesia in dogs.

The effect of the alpha 2-agonist dexmedetomidine on the cerebral blood flow (CBF) and the metabolic rate for oxygen was studied by a sagittal sinus outflow technique in dogs during halothane anesthesia. Dexmedetomidine was given in a dose (10 micrograms/kg) reported to reduce the anesthetic requirement of halothane by 90%. During 0.9% halothane anesthesia dexmedetomidine caused a significant reduction in CBF without influencing the metabolic rate for oxygen. Reducing the halothane concentration to 0.1% caused no further change in CBF, but increased the metabolic rate for oxygen 19%. The cerebral vasoconstrictive effect, combined with the 90% reduction in MAC for halothane, indicates that dexmedetomidine might be a useful adjunct to inhalation anesthetics during neurosurgery in situations where an increase in CBF should be avoided.

Bilateral involvement and the effect of sympathetic blockade on skin microcirculation in the sympathetic dystrophies.

In a recent study we found skin capillary blood cell velocity (CBV) at rest, laser Doppler flux (LDF), and its response to lowering of the hand to be reduced in the dystrophic hand of patients suffering from sympathetic dystrophies. This study confirms these previous findings. Four of the 12 patients investigated felt intermittent pain in the "healthy" hand. Basal CBV, LDF, and reaction during dependency were not impaired in the asymptomatic hand compared with controls. However, during cooling of the contralateral hand CBV and LDF decreased significantly (median 44 and 37.5%) in the control group but neither in the affected nor in the asymptomatic hand among patients. Sympathetic blockade significantly increased both CBV and LDF in the dystrophic hand (median 58 and 20%), but no obvious beneficial symptomatic effect was noted. The lack of response to contralateral cooling in both hands indicates a disturbance of a central nervous mechanism in patients with unilateral sympathetic dystrophies.

The effects of prolonged isoflurane anaesthesia on cerebral blood flow and metabolism in the dog.

To determine whether cerebral blood flow (CBF) changed with time under isoflurane anaesthesia, as has been reported for halothane, CBF and cerebral metabolic rate for oxygen (CMRO2) were studied in five dogs under prolonged isoflurane anaesthesia. CBF was measured with a modified sagittal sinus technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Maintaining this experimental dog model with 1% isoflurane in oxygen and nitrogen for 3 h in five dogs and for 4 h in three dogs did not cause any significant changes in CMRO2 or CBF. Cerebral metabolite levels were consistent with earlier reports from short-time studies and the EEG recordings showed a continuous sleep pattern with no pathological changes. It is concluded that there is no change in CBF or CMRO2 in our modified sagittal outflow model during 3-4 h of 1% isoflurane anaesthesia.

Partial reversal of the cerebral effects of isoflurane in the dog by the benzodiazepine antagonist flumazenil.

Six dogs initially anaesthetized with isoflurane-N2O-O2 for surgery with cannulation of the sinus sagittalis for direct measurement of cerebral blood flow (CBF) and maintained with 1% isoflurane-N2-O2 anaesthesia, were given two 2-mg doses of the benzodiazepine antagonist flumazenil with an interval of 10 min. This was accompanied by a significant increase in the cerebral metabolic rate for oxygen (CMRO2) 10 min after the first 2-mg dose, and 5, 10 and 15 min after the second 2-mg dose, the increase varying in mean value from 9% to 14%. EEG was recorded in five of the six dogs and administration of flumazenil converted the EEG from a sleep pattern to an awake pattern in two of them. There were no significant changes in the CBF or mean arterial blood pressure (MABP) values. In the brain biopsies taken at the end of the study there were no significant changes in the adenylate energy charge (EC) and the lactate/pyruvate ratio (L/P) when compared to five other dogs not given flumazenil. It is concluded that flumazenil in this study demonstrated a partial antagonism of the cerebral effects of isoflurane.

Reversal of the cerebral effects of diazepam in the dog by the benzodiazepine antagonist Ro15-1788.

In six dogs initially anesthetized with halothane-N2O-O2 for surgery and maintained during the experiment with high spinal anesthesia and local infiltration, diazepam 3.0 mg X kg-1 converted the EEG from an awake to a sleep pattern. This was accompanied by a significant 21% reduction in cerebral metabolic rate for oxygen (CMRO2) and a 15% reduction in cerebral blood flow (CBF). Substituting nitrous oxide 70% for nitrogen had no additional cerebral effects. The benzodiazepine antagonist Ro15-1788, 2 mg, completely reversed the effects of diazepam on the EEG, CMRO2 and CBF. Cerebral biopsies taken at the end of the study revealed modest but significant decreases in ATP and the energy charge along with increases in AMP, lactate and lactate/pyruvate (L/P) ratio. These changes are unexplained and suggest a possible disturbance in oxidative phosphorylation produced by Ro15-1788 preceded by diazepam.

The effects of triazolam on cerebral blood flow and metabolism in the dog.

The new benzodiazepine triazolam was given to six initially awake dogs maintained with spinal anaesthesia and mechanical ventilation. Both cerebral blood flow (CBF) and cerebral metabolic rate for O2 (CMRO2) were significantly reduced after the initial dose of 0.1 mg X kg-1 triazolam, and the EEG changed from an awake to a sleep pattern in less than 20 s. CMRO2 was gradually reduced with increasing doses of triazolam (0.3, 1.0, 10.0 and 30.0 mg X kg-1) to 76% of control after the final 30 mg X kg-1 dose. CBF did not decrease further after the initial dose, and the addition of N2O after the final dose did not cause any significant change in CBF or CMRO2. The dogs were hemodynamically stable during the study. Small increases in brain lactate and pyruvate levels, but not in the L/P ratio were the only significant changes in brain metabolite levels. Triazolam appears to be a safe and rapidly acting induction agent in the dog.

Treatment of Raynaud's phenomenon with ketanserin in patients with connective tissue disorders.

The serotonin receptor blocker ketanserin was given orally in a double blind crossover study to 10 patients with connective tissue disorders and Raynaud's phenomenon. Eight of the 10 patients improved clinically on ketanserin and none on placebo. Digital blood flow was assessed with laser Doppler flowmetry (LDF), photoplethysmography, and skin temperature measurements. Laser Doppler flowmetry was the most useful method, showing a significant reduction in recovery time after a standard cold provocation. Although the resting flow was not significantly improved, digital ulcers healed in four out of five patients, providing evidence of increased nutritive flow. The results of this study suggest that orally administered ketanserin may be an effective and well tolerated treatment for Raynaud's phenomenon associated with connective tissue disorders, especially scleroderma.

Treatment of Raynaud's phenomenon with the 5-HT2-receptor antagonist ketanserin.

The selective 5-hydroxytryptamine2-(5-HT2)-receptor-blocking agent ketanserin was given in a dose of 10 mg intravenously to nine patients with Raynaud's phenomenon. The effect on blood flow was assessed by photopletysmography and measurments of skin temperature. Digital blood flow and skin temperature increased significantly after ketanserin injection, whereas the placebo (saline 9 g/l) had no such effect. This study suggests that ketanserin may be useful in the treatment of Raynaud's phenomenon.