Isoflurane and halothane cause electroencephalographic (EEG) depression and neuronal depression in the reticular formation, a site critical to consciousness. We hypothesized that isoflurane, more than halothane, would depress EEG activation elicited by electrical microstimulation of the reticular formation. Rats were anesthetized with either halothane or isoflurane and stimulating electrodes were positioned in the reticular formation. In a crossover design, anesthetic concentration was adjusted to 0.8 and 1.2 minimum alveolar concentration (MAC) of halothane or isoflurane and electrical microstimulation was performed and the EEG responses were recorded. Microstimulation increased the spectral edge and median edge frequencies 2-2.5 Hz at 0.8 MAC for halothane and isoflurane and 1.2 MAC halothane. At 1.2 MAC isoflurane, burst suppression occurred and microstimulation decreased the period of isoelectricity (24% +/- 19% to 8% +/- 7%; P < 0.05), whereas the spectral edge and median edge frequencies were unchanged. At anesthetic concentrations required to produce immobility, the cortex remains responsive to electrical microstimulation of the reticular formation, although the EEG response is depressed in the transition from 0.8 to 1.2 MAC. These data indicate that cortical neurons remain responsive to synaptic input during isoflurane and halothane anesthesia.

Left ventricular failure is a condition that is characterized by chronic pulmonary venous congestion interspersed by episodes of acute pulmonary alveolar oedema. Previous investigations from this laboratory have demonstrated that the activity of rapidly adapting receptors (RARs) are influenced by fluid fluxes from microvasculature of the airways (Hargreaves et al. 1991). RARs have been shown to respond to acute pulmonary venous congestion with a sustained increase in activity. In those experiments, pulmonary venous congestion was caused by partial obstruction of the mitral valve to raise the left atrial pressure (LAP) by 5-10 mmHg. Since left ventricular failure usually presents as acute exacerbation of a chronic condition, it is of interest to determine whether the functions of the RARs are modified by persistent mild pulmonary venous congestion. The experiments reported in this paper were undertaken to test the hypothesis that the increase in RAR activity resulting from small acute increments of LAP (5 and 10 mmHg) was attenuated in animals maintained in a state of chronic pulmonary venous congestion. Chronic pulmonary venous congestion was produced surgically by partial destruction of the mitral valve. The experiments were undertaken in anaesthetized New Zealand White rabbits. The data from these animals were compared with intact control animals and sham-operated animals. METHODSExperiments were performed on forty-five male New Zealand White rabbits weighing 3·28 ± 0·05 kg (range 2·7-3·8 kg). The protocol was approved by the Animal Use and Care Committee of the University of California, Davis. Two groups of rabbits were studied: intact (control) rabbits and those with surgically induced mitral regurgitation. They were pre-medicated with ketamine HCl (50 mg kg¢, Mallinckrodt Veterinary Inc., Mundelein, IL, USA) and xylazine (5 mg kg¢, Bayer, Shawnee Mission, KA, USA) i.m., and then anaesthetized with pentobarbitone sodium (5 mg kg¢, Veterinary Laboratories Inc., Lenexa, KA, USA) given through an ear vein. Anaesthesia was maintained with pentobarbitone sodium (4 mg kg¢, Veterinary Laboratories Inc.) i.v. every half an hour. After induction of anaesthesia an uncuffed endotracheal tube (i.d. 3 mm and length 5 cm) was introduced through a tracheostomy and was tied in place. The rabbits were artificially ventilated (Model 55- 1. The effects of acute pulmonary venous congestion on the activity of rapidly adapting receptors (RARs) were determined in intact (control and sham-operated) rabbits and in rabbits 6 and 12 weeks after surgical destruction of the mitral valve. 2. Destruction of the mitral valve increased the mean left atrial pressure (LAP) by approximately 2·6 and 3·8 mmHg, 6 and 12 weeks after surgery, respectively. These changes were accompanied by significant increases in left ventricular weight. The effect of acute increments in LAP on RAR activity was examined against this background of chronic pulmonary venous congestion. 3. In intact control and sham-operated animals RAR activity increased from 48·8 ± ...

These data suggest that HFB, like halothane, produces immobility, predominantly by a spinal cord action, and that HFB differs from ODFB with respect to brain versus spinal sites of action. Nonetheless, although ODFB can produce immobility via a cerebral action, it also can do this via an independent action in the spinal cord. Thus, our results continue to support the spinal cord as the primary site at which inhaled anesthetics, and perhaps propofol, produce immobility.

Pulmonary rapidly adapting receptors (RARs) in anaesthetized intact rabbits are activated by small changes in the extravascular fluid spaces of the major airways where they are located (Hargreaves et al. 1991). It has also been shown that stimulation of RARs in this manner causes reflex increases in respiratory rate (Kappagoda et al. 1989), tracheal tone (Kappagoda et al. 1988) and mucus production by the respiratory epithelium (Yu et al. 1989). All these reflex effects collectively form the syndrome of cardiac asthma which is characterized by wheezing, an increased respiratory rate and increased mucus production. Therefore, it was suggested that in chronic left ventricular dysfunction, intermittent, small acute elevations of left atrial pressure (LAP) cause these exacerbations in symptoms through activation of RARs (Hargreaves et al. 1991). However, in a recent study from our laboratory performed on rabbits maintained in a state of chronic pulmonary venous congestion (PVC) secondary to surgically induced mitral regurgitation (MR), acute small elevations (+10 mmHg) of LAP failed to activate RARs (Gunawardena et al. 1998). It was speculated that in these animals this lack of response of RARs could be due to a change either in the receptor per se, or in the extravascular space surrounding the receptor. These issues were addressed in the present study by testing the following hypotheses: (i) shrinking the extravascular space by an intravenous infusion of hypertonic albumin restores the sensitivity of previously insensitive RARs (to small, acute elevations of LAP) in rabbits with chronic PVC, (ii) the increase in extravascular fluid volume in major airways resulting from small elevations of LAP is less in animals with chronic PVC than in age-matched control animals, and (iii) enhancing the stimulus to RARs by increasing the LAP above 25 mmHg stimulates previously insensitive RARs in rabbits with chronic PVC. As in the 1. Unlike in normal rabbits, pulmonary rapidly adapting receptors (RARs) in rabbits with chronic mitral regurgitation (MR) do not respond to small changes in extravascular fluid (EVF) volume in major airways. The present study examined the effect of shrinking the EVF volume in rabbits with chronic MR by infusing hypertonic albumin, to see whether this response of RARs is restored. The effect of raising the left atrial pressure (LAP) acutely above 25 mmHg (to cause pulmonary oedema) on RARs was also investigated. 2. Mean RAR activities in rabbits with MR (n = 6) at initial control, LAP +5 mmHg, LAP +10 mmHg and final control periods were 20·9 ± 9·5, 18·8 ± 11·3, 27·0 ± 11·2 and 17·2 ± 9·8 action potentials min¢, respectively (P > 0·05, ANOVA). After infusion of 35% bovine serum albumin i.v. these values were 9·4 ± 3·2, 30·6 ± 14·6, 48·9 ± 10·1 and 18·4 ± 7·3 action potentials min¢, respectively (P < 0·01, ANOVA). In rabbits with chronic MR (n = 7) raising the LAP above 25 mmHg stimulated RARs. 3. EVF content of the airways and lungs was measured in rabbits with MR and in control rabbits, at baseline and...

The role of adrenergic receptors in the reflex diuresis in response to pulmonary lymphatic drainage was examined in anaesthetized, artificially ventilated New Zealand White rabbits. Pulmonary lymphatic drainage was obstructed by raising the pressure in a pouch created from the right external jugular vein. This pulmonary lymphatic obstruction results in a reflex increase in urine flow and sodium excretion. This reflex is abolished by renal denervation and by administration of L-NAME, a non-selective inhibitor of nitric oxide synthase. Also, infusion of the relatively selective neuronal nitric oxide synthase blocker, 7-nitroindazole sodium salt, into the renal medulla abolished the reflex diuresis. In this study the effects of adrenergic receptor antagonists on the reflex increase in urine were observed. Both ureters were cannulated in order to determine urine flow from both kidneys separately. Prazosin, an α 1 adrenergic receptor antagonist, was infused into the renal medulla of the right kidney, while the left kidney acted as control. Administration of prazosin in this manner did not block the reflex diuresis in response to pulmonary lymphatic obstruction in either kidney. However, rauwolscine, an α 2 adrenergic receptor antagonist, abolished the reflex increase in urine and sodium excretion in the ipsilateral kidney while preserving it in the contralateral kidney. These findings suggest that the increase in urine flow in rabbits caused by pulmonary lymphatic obstruction is dependent upon activation of α 2 adrenergic receptors within the renal medulla.