Sage Journals: Discover world-class research

Abstract

The noble gas xenon seems to have minimal cardiovascular side-effects and so may be an ideal anaesthetic agent when investigating cardiovascular physiology. In comparison with standard modern anaesthetics, we investigated the haemodynamic and hormonal effects of xenon in Beagle dogs. After a 30 min baseline period, anaesthesia was induced with propofol and maintained with either (1) 1.2% isoflurane/70% nitrous oxide (N₂O), (2) 0.8% isoflurane/0.5 µg/kg/min remifentanil or (3) 63% xenon/0.5 µg/kg/min remifentanil (n = 6 per group). Haemodynamics were recorded and blood samples taken before and 60 min after induction. Mean arterial blood pressure (MAP) was higher in conscious dogs than during isoflurane/N₂O (86 ± 2 vs. 65 ± 2 mmHg, mean ± SEM) and isoflurane/remifentanil anaesthesia (95 ± 2 vs. 67 ± 3 mmHg), whereas MAP did not decrease significantly in response to xenon/remifentanil anaesthesia (96 ± 4 vs. 85 ± 6 mmHg). Bradycardia was present during isoflurane/remifentanil (54 ± 2/min) and xenon/remifentanil (40 ± 3/min), but not during isoflurane/N₂O anaesthesia (98 ± 3/min, P < 0.05). Xenon/remifentanil anaesthesia induced the highest reduction in cardiac output (CO) (–61%), and the highest increase in systemic vascular resistance (+120%) among all treatment groups (P < 0.05). A simultaneous increase in endogenous adrenaline and noradrenaline concentrations could only be observed in the xenon/remifentanil group, whereas angiotensin II and vasopressin concentrations increased in all groups. In conclusion, xenon/remifentanil anaesthesia maintains MAP but reduces heart rate and CO and is associated with a considerable stimulation of vasopressor hormones in Beagle dogs. Therefore, xenon/remifentanil exerts a new quality of adverse haemodynamic effects different from volatile anaesthetics and may not perform better during studies of cardiovascular physiology.

Keywords

Anaesthesia cardiovascular haemodynamic catecholamine xenon

It is generally agreed that cardiovascular physiological research should as far as possible be conducted on conscious individuals or animals in order to avoid anaesthesia-induced haemodynamic and hormonal side-effects (Burchardi & Kaczmarczyk 1994, Hettrick et al. 1996, Preckel et al. 2004). However, if the experimental protocol includes painful and stressful procedures general anaesthesia is essential. It is not yet clear what the optimal anaesthetic technique for this type of study is. A wide range of anaesthetic agents are now available and can be used especially in bigger animals like pigs and dogs as well as in humans. Xenon as an anaesthetic may prove to be superior to other anaesthetic agents (Lane et al. 1980, Lynch et al. 2000). It is of special interest to the physiologist because it is highly cardiostable. Blood pressure and left ventricular performance are not or minimally affected in dogs (Hettrick et al. 1998), pigs (Marx et al. 1997) and humans (Luttropp et al. 1993, Ishiguro 2001). Moreover, a randomized, controlled multicentre trial by Rossaint et al. (2003) has shown xenon anaesthesia to be clinically effective and safe.

However, there are reports that xenon may potentiate parasympathetic activity, depress heart rate (HR) variability and depress baroreflex sensitivity to a greater extent than isoflurane (Ishiguro et al. 2000). The literature on catecholamine release during xenon anaesthesia is equivocal. Some studies report a decrease of plasma catecholamine concentrations during anaesthesia in pigs (Marx et al. 1997), and unaltered or elevated catecholamine concentrations during xenon anaesthesia in human patients (Boomsma et al. 1990). Against this background of conflicting reports regarding the cardiovascular and hormonal effects of xenon, we performed this randomized controlled study in one of the most widely studied animal models of cardiac physiology – the Beagle dog. We compared a combination of xenon and remifentanil with two well-established regimens: isoflurane/remifentanil and isoflurane/N₂O. We hypothesized that a combination of xenon and remifentanil results in less cardiovascular and hormonal disturbance than two widely used isoflurane-based regimens.

Materials and methods

The study was approved by the local Governmental Animal Protection Committee (Permission No. G0424/99) and adheres to the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Research, Commission on Life Sciences, National Research Council 1996).

Animal maintenance and dietary regimen

Healthy, pure-bred female Beagle dogs (mean body weight: 13.4 ± 1.3 kg) of, on average, two years of age were kept under highly standardized environmental conditions (air-conditioning at 21°C and 55–60% humidity) and received a dietary regimen which was standardized for sodium (2.5 mmol/kg body weight per day) and water (91 mL/kg body weight per day) intake as described previously (Höhne et al. 2002, Francis et al. 2004). Daily check-ups on physical health included body weight and temperature measurement.

Eight days prior to the experiments, an aliquot (max. 80 mL) of each dog's own blood was collected and stored in a blood bag at 4°C (Biopack^®; Biotrans, Dreieich, Germany). The blood served to replace the blood withdrawn for analysis during the experiments. We maintained an interval of at least 14 days between experiments in the same dog in order to avoid possible interactions between the different anaesthetics. Six months after all experiments had been performed, the dogs were subject to a final veterinary examination for health and wellbeing, and were then removed from the laboratory to live with individual families in private housing. The families were all familiar with dog keeping and were aware of the dogs' past history.

Experimental protocols

A total of six dogs were investigated. During a training period of at least six weeks, the dogs were gradually familiarized with the laboratory environment, the staff of investigators and the experimental procedures. The training period has been described in detail previously (Höhne et al. 2002, Francis et al. 2004). The staff of investigators could provide a calming influence on the dogs by voice and petting. None of the dogs displayed noticeable problems regarding their psychological status in the training period, and there was no adverse social behaviour towards the staff of investigators nor towards the other dogs which were kept in close company. Each dog was subject to three different treatments in random order, which resulted in a total of 18 experiments. Only one experiment was performed per day. Preparation of the dogs started at 07:30 h. Body weight and temperature were recorded. The bladder was catheterized with a self-retaining transurethral Foley catheter and a venous cannula was placed into a foreleg vein.

Insertion of intravascular catheters was performed under local anaesthesia (lidocaine 1%). An arterial line (20 gauge, No. 4235-8; Ohmeda, Erlangen, Germany) was positioned in the abdominal aorta via the femoral artery and was used for pressure monitoring and blood sampling. A pulmonary artery catheter (5 French, No. 132F5; Baxter, Unterschließheim, Germany) was then inserted via the right external jugular vein for monitoring of mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), determination of cardiac output (CO) (using the transpulmonary thermodilution method) and blood sampling. The arterial line and the pulmonary artery catheter were connected to pressure transducers (Viggo Spectramed, DF-XX, Spectramed GmbH, Düsseldorf, Germany) which were attached to a vertical upright centimetre scale on the table. The transducers were levelled at the right atrium of the dogs (on the centimetre scale this is about 10–11 cm above the table) who were lying on their right side throughout the experiment. The transducer position was recorded and used for all further experiments in the respective dog. Following this, the conscious dogs were allowed to adjust for at least 30 min before the experiment was started at 09:30 h.

After a baseline period of 30 min in the conscious state, anaesthesia was induced with propofol 8–10 mg/kg (Disoprivan^® 1% lipid emulsion; AstraZeneca GmbH, Wedel, Germany) and the dogs were intubated with a cuffed Woodbridge tube (34–36 Charrière) and mechanically ventilated on a closed circuit system (PhysioFlex^TM, Dräger Medical, Lübeck, Germany) in a volume-controlled mode with an I/E ratio of 1:2. The respiratory rate was set to 12 breaths/min, the positive end-expiratory pressure to 4 mmHg and the tidal volume was adjusted to keep the arterial carbon dioxide tension between 35 and 40 mmHg. General anaesthesia was then maintained by one out of three different anaesthetic regimens (described below).

Isoflurane/N₂O

The inspired concentration of isoflurane was adjusted to maintain an end-tidal concentration of 1.2 ± 0.03 vol% in a mixture of 30% oxygen and 70% N₂O. This was equivalent to 1.3 times the minimal anaesthetic concentration (MAC) in dogs (5), because 1 MAC is 1.28 vol% for isoflurane and 188 vol% for N₂O in dogs. These two MAC values are additive (Cullen 1986).

MAC of an inhaled anaesthetic is defined as that concentration at 1 atmosphere that prevents skeletal muscle movement in response to a supramaximal painful stimulus (e.g. tail clamp or surgical incision) in 50% of patients. A MAC of 1.3 prevents response in 95% of subjects.

Isoflurane/remifentanil

The inspired concentration of isoflurane was adjusted to an end-tidal concentration of 0.8 ± 0.01 vol% in a mixture of oxygen and air (inspiratory oxygen concentration 26 ± 1%). Remifentanil was simultaneously infused at 0.5 µg/kg/min. This dosage of remifentanil has been shown to reduce the MAC of enflurane by about 50% in dogs (Michelsen et al. 1996). We were unable to locate any data on the effect of remifentanil on the MAC of isoflurane in dogs. It is known that remifentanil at a whole blood concentration of 1.37 ng/mL reduces the MAC of isoflurane in humans by 50% (Lang et al. 1996). We therefore presumed that in dogs the MAC of isoflurane should be reduced by approximately 50% when combined with a similar dosage of remifentanil and so targeted an end-tidal isoflurane concentration of 0.8 vol%, which we estimated to be equivalent to a MAC of 1.3.

Xenon/remifentanil

We maintained an end-tidal concentration of xenon of 63 ± 1 vol% with an inspiratory oxygen concentration of 29 ± 1%. Remifentanil was infused at 0.5 µg/kg/min. The MAC of xenon in dogs is 120% (Eger et al. 1965a) and so is impossible to apply under normobaric conditions. We therefore decided to use the highest concentration of xenon possible without risking hypoxia combined with the same dosage of remifentanil (0.5 µg/kg/min) as desribed above.

Depth of anaesthesia was assessed by eyelash reflex testing and by standardized tail-clamping (Eger et al. 1965b) and observation for signs such as tail wagging, eyelash reflex or movement of the limbs. Depth of anaesthesia was determined to be adequate in all cases. Animals were unrestrained and no neuromuscular blockade was used.

Measurements and calculations

HR, mean arterial blood pressure (MAP) and central venous pressure (CVP) were measured continuously, and data were stored on a computer. Measurements were begun before induction of anaesthesia and continued for 60 min during anaesthesia. CO was determined by transpulmonary thermodilution (5 mL injection volume at 5–10°C; Vigilance^®, Baxter, Unterschleißheim, Germany). Five consecutive measurements were performed, the highest and the lowest values were rejected and the mean CO was calculated from the three remaining values (Jansen et al. 1990). Systemic (SVR) and pulmonary vascular resistance (PVR) and stroke volume (SV) were calculated by standard formulas: SVR = (MAP–CVP) × 80/CO; PVR = (MPAP−PCWP) × 80/CO; SV = CO/HR. Blood samples were taken to determine plasma hormones, plasma osmolarity (Osmometer 2, Fa. Roebling, Berlin, Germany), plasma electrolytes (flame photometry, AFM 5052, Eppendorf GmbH, Hamburg, Germany), arterial and mixed venous blood gases and base excess (ABL 505 analyser, Radiometer, Copenhagen, Denmark). Systemic oxygen consumption and delivery were calculated by standard formulas:

D˙O₂(mL/min) = CO(SaO₂[%] × Hb[g/dL] × 1.34[mL/g] + PaO₂ [mmHg] × 0.003)

V˙O₂(mL/min) = CO(Hb [g/dL] × 1.34 [mL/g] × (SaO₂ [%]–SvO₂ [%]) + 0.003 (PaO₂ [mmHg]–PvO₂ [mmHg])).

The blood withdrawn for analysis was immediately replaced with an equal amount of each dog's own blood precollected eight days previously. Blood samples were cooled and centrifuged at 4°C. Plasma was then stored at –20°C until analysis of plasma renin activity (New England Nuclear, North Billerica, MA, USA), angiotensin II (Eurodiagnostika, Arnhem, The Netherlands), atrial natriuretic peptide (Eurodiagnostika), aldosterone (DiaSorin GmbH, Düsseldorf, Germany) or vasopressin (Vasopressin-RIA, Biermann GmbH, Bad Nauheim, Germany) with radioimmunoassays, or with enzyme-linked immunosorbent assay as for plasma endothelin-1 (Biomedica, Austria). Adrenaline and noradrenaline were determined by high-performance liquid chromatography (Chromosystems, Munich, Germany) in serum that had been stored at –80°C.

Statistical analysis

All values are quoted as means ± SEM. A general linear model of analysis of variance (GLM ANOVA) for repeated measures was applied. Based on the ANOVA results, post hoc testing was performed with Student's t-test. The level of significance for first-order error was adjusted according to Holm's procedure (Schaffer 1986). Statistical significance was assumed at P < 0.05.

Results

Haemodynamics

From its baseline awake level, MAP decreased upon the induction and maintenance of anaesthesia in both the isoflurane/N₂O and the isoflurane/remifentanil groups. During xenon/remifentanil anaesthesia, however, MAP remained constant (Table 1). HR (Table 1) increased during isoflurane/N₂O but decreased during isoflurane/remifentanil and xenon/remifentanil anaesthesia. CO (Table 1) was between 2.2 and 2.3 L/min in awake dogs and decreased by 27 ± 0.04% (isoflurane/N₂O), 47 ± 0.04% (isoflurane/remifentanil) and 61 ± 0.04% (xenon/remifentanil). A decrease in SV (Table 1) was present in all protocols. Simultaneously, SVR remained stable during isoflurane/N₂O (+4%, n.s.), but increased by 30% during isoflurane/remifentanil and by 120% during xenon/remifentanil anaesthesia (Table 1). CVP ranged between 1 and 3 cmH₂O in awake dogs, and rose during isoflurane/remifentanil and xenon/remifentanil anaesthesia. CVP was highest during xenon/remifentanil anaesthesia (8 ± 1 cmH₂O). Likewise, the increase in PCWP was exaggerated during xenon/remifentanil anaesthesia (Table 1). MPAP was 12 ± 1 mmHg and PVR was similar in conscious dogs of all treatment groups. MPAP increased during xenon/remifentanil anaesthesia, whereas it remained constant during the other protocols (Table 1).
Table 1
Haemodynamic parameters

Awake Anaesthesia

Heart rate, beats/min

Isoflurane/N₂O 88 ± 3 98 ± 3^†

Isoflurane/remifentanil 77 ± 5 54 ± 2^†

Xenon/remifentanil 86 ± 4 40 ± 3

Cardiac output, L/min

Isoflurane/N₂O 2.2 ± 0.1 1.6 ± 0.1^†

Isoflurane/remifentanil 2.3 ± 0.2 1.2 ± 0.1^†

Xenon/remifentanil 2.3 ± 0.2 0.9 ± 0.1*

Stroke volume, mL

Isoflurane/N₂O 26 ± 2 17 ± 1*

Isoflurane/remifentanil 29 ± 2 23 ± 2*

Xenon/remifentanil 27 ± 2 23 ± 2*

MAP, mmHg

Isoflurane/N₂O 86 ± 2 65 ± 2^†

Isoflurane/remifentanil 95 ± 2 67 ± 3^†

Xenon/remifentanil 96 ± 4 85 ± 6

Systemic vascular resistance, dyn seconds/cm⁵

Isoflurane/N₂O 3025 ± 211 3148 ± 121^†

Isoflurane/remifentanil 3387 ± 309 4443 ± 369^†

Xenon/remifentanil 3282 ± 281 7231 ± 803

Mean pulmonary artery pressure, mmHg

Isoflurane/N₂O 12 ± 1 13 ± 1^†

Isoflurane/remifentanil 12 ± 1 11 ± 1^†

Xenon/remifentanil 12 ± 1 16 ± 1*

Pulmonary vascular resistance, dyn seconds/cm⁵

Isoflurane/N₂O 350 ± 20 452 ± 32^†

Isoflurane/remifentanil 376 ± 52 557 ± 24

Xenon/remifentanil 365 ± 54 652 ± 55*

Central venous pressure, cmH₂O

Isoflurane/N₂O 2 ± 0.2 2 ± 0.2^†

Isoflurane/remifentanil 1 ± 1 3 ± 1^†

Xenon/remifentanil 3 ± 1 8 ± 1

Pulmonary capillary wedge pressure, cmH₂O

Isoflurane/N₂O 2 ± 0.3 4 ± 0.4^†

Isoflurane/remifentanil 1 ± 0.3 3 ± 0.4^†

Xenon/remifentanil 2 ± 0.7 9 ± 0.9*

Values are presented as means ± SEM; n = 6. Values were measured after 30 min awake and after 60 min of anaesthesia

P < 0.05 versus awake

^† P < 0.05 versus xenon/remifentanil

N₂O: nitrous oxide; MAP: mean arterial blood pressure

Plasma hormones

Plasma hormone concentrations were similar in awake dogs (Table 2, Figures 1 and 2). Plasma renin activity increased up to 10-fold during anaesthesia with no significant differences between protocols. Simultaneously, angiotensin II levels (Figure 1) increased during all types of anaesthesia, but this increase was attenuated during isoflurane/N₂O anaesthesia. Angiotensin II plasma concentrations were parallelled by plasma concentrations of aldosterone (Table 2). Vasopressin concentrations increased during all anaesthesia regimens, but were highest during xenon/remifentanil anaesthesia (Figure 1). Interestingly, adrenaline and noradrenaline concentrations (Figure 2) rose only during xenon/remifentanil anaesthesia, but did not rise during both the isoflurane protocols. No substantial changes in plasma endothelin concentrations could be observed during the experiments. Only small variations were found for atrial natriuretic peptide during anaesthesia (Table 2).
Figure 1
Plasma concentrations of angiotensin II (a) and vasopressin (b) in awake dogs and after 60 min of anaesthesia. Values are presented as means ± SEM; n = 6. P < 0.05 versus awake; ^† P < 0.05 versus xenon/remifentanil. N₂O: nitrous oxide. Error bars may not be visible when SEM is smaller than symbol size

Figure 2
Plasma concentrations of adrenaline (a) and noradrenaline (b) in awake dogs and after 60 min of anaesthesia. Values are presented as means ± SEM; n = 6. P < 0.05 versus awake; ^† P < 0.05 versus xenon/remifentanil. N₂O: nitrous oxide. Error bars may not be visible when SEM is smaller than symbol size

Table 2
Plasma hormones

Awake Anaesthesia

Renin activity, ngAngI/mL/h

Isoflurane/N₂O 3.4 ± 0.6 24.9 ± 2.9

Isoflurane/remifentanil 3.1 ± 0.6 31.8 ± 5.7*

Xenon/remifentanil 3.7 ± 0.9 20.2 ± 3.2*

Aldosterone, pg/mL

Isoflurane/N₂O 78 ± 14 672 ± 52*

Isoflurane/remifentanil 100 ± 22 1114 ± 57^†

Xenon/remifentanil 89 ± 20 700 ± 140

Endothelin-1, pg/mL

Isoflurane/N₂O 1.0 ± 0.1 1.1 ± 0.1

Isoflurane/remifentanil 1.0 ± 0.2 1.1 ± 0.2

Xenon/remifentanil 0.9 ± 0.1 1.2 ± 0.1*

Atrial natriuretic peptide, pg/mL

Isoflurane/N₂O 60 ± 8 42 ± 7^†

Isoflurane/remifentanil 68 ± 7 73 ± 7

Xenon/remifentanil 57 ± 6 63 ± 3

Values are presented as means ± SEM; n = 6. Values were measured after 30 min awake and after 60 min of anaesthesia

P < 0.05 versus awake

^† P < 0.05 versus xenon/remifentanil

N₂O: nitrous oxide

Blood gases and oxygen consumption

Arterial oxygen tension increased after induction of anaesthesia as a result of the elevated fraction of inspired oxygen supplied via the ventilator (F_iO₂; see Table 3). Slight differences in arterial oxygen tension (P_aO₂) between protocols match slight differences in F_iO₂. Arterial carbon dioxide tension (P_aCO₂) indicated normoventilation in all protocols. Arterial pH was within normal limits in all protocols, but decreased slightly during xenon/remifentanil anaesthesia. Arterial base excess decreased in all protocols during anaesthesia with no difference between protocols. Mixed venous oxygen saturation was constant only during isoflurane/N₂O anaesthesia, but decreased in the other protocols, parallelled by simultaneous changes in mixed venous oxygen tension. Systemic oxygen delivery (Table 4) was reduced during anaesthesia in all protocols. Systemic oxygen consumption (Table 4) declined during isoflurane/N₂O and xenon/remifentanil anaesthesia. Arterial to mixed venous difference in oxygen content (Table 4) increased during xenon/remifentanil and isoflurane/remifentanil anaesthesia but remained constant during isoflurane/N₂O anaesthesia.
Table 3
Inspired fraction of oxygen, blood gases, pH and base excess

Awake Anaesthesia

F_iO₂

Isoflurane/N₂O Ambient air 0.33 ± 0.01^†

Isoflurane/remifentanil Ambient air 0.26 ± 0.01^†

Xenon/remifentanil Ambient air 0.29 ± 0.01

P_aO₂, mmHg

Isoflurane/N₂O 95 ± 1 181 ± 3^†

Isoflurane/remifentanil 99 ± 2 138 ± 15

Xenon/remifentanil 98 ± 1 143 ± 6*

P_vO₂, mmHg

Isoflurane/N₂O 44 ± 1 47 ± 1^†

Isoflurane/remifentanil 48 ± 2 38 ± 1*

Xenon/remifentanil 46 ± 2 39 ± 1*

P_aCO₂, mmHg

Isoflurane/N₂O 35 ± 1 35 ± 1

Isoflurane/remifentanil 35 ± 1 38 ± 1

Xenon/remifentanil 37 ± 1 37 ± 1

pH_a

Isoflurane/N₂O 7.39 ± 0.01 7.38 ± 0.01

Isoflurane/remifentanil 7.39 ± 0.01 7.38 ± 0.01

Xenon/remifentanil 7.39 ± 0.01 7.35 ± 0.01*

BE_a, mmol/L

Isoflurane/N₂O −2.2 ± 0.7 −4.2 ± 0.3*

Isoflurane/remifentanil −2.4 ± 0.5 −3.7 ± 0.5*

Xenon/remifentanil −2.5 ± 0.5 −5.0 ± 0.6*

S_aO₂, %

Isoflurane/N₂O 98 ± 0.2 100 ± 0.1*

Isoflurane/remifentanil 99 ± 0.2 100 ± 0.1

Xenon/remifentanil 99 ± 0.4 100 ± 0.2

S_vO₂, %

Isoflurane/N₂O 80 ± 3 82 ± 1^†

Isoflurane/remifentanil 83 ± 2 69 ± 2*

Xenon/remifentanil 81 ± 2 67 ± 2*

Values are presented as means ± SEM; n = 6. Values were measured after 30 min awake and after 60 min of anaesthesia

P < 0.05 versus awake

^† P < 0.05 versus xenon/remifentanil

N₂O: nitrous oxide; F_iO₂: inspired fraction of oxygen; P_aO₂: arterial oxygen tension; P_vO₂: mixed venous oxygen tension; P_aCO₂: arterial carbon dioxide tension; pH_a: arterial pH; BE_a: arterial base excess; S_aO₂: arterial haemoglobin oxygen saturation; S_vO₂: mixed venous haemoglobin oxygen saturation

Table 4
Oxygen delivery, consumption and extraction

Awake Anaesthesia

D˙O₂, mL/min

Isoflurane/N₂O 381 ± 39 238 ± 22

Isoflurane/remifentanil 412 ± 52 196 ± 18*

Xenon/remifentanil 426 ± 43 179 ± 14*

V˙O₂, mL/min

Isoflurane/N₂O 68 ± 2 48 ± 4*

Isoflurane/remifentanil 68 ± 5 61 ± 3

Xenon/remifentanil 76 ± 3 58 ± 3*

C_(a−v)O₂, mL/dL

Isoflurane/N₂O 3.1 ± 0.3 2.9 ± 0.3^†

Isoflurane/remifentanil 2.8 ± 0.3 5.2 ± 0.2^†

Xenon/remifentanil 3.4 ± 0.2 6.7 ± 0.4

Values are presented as means ± SEM; n = 6. Values were measured after 30 min awake and after 60 min of anaesthesia

P < 0.05 versus awake

^† P < 0.05 versus xenon/remifentanil

N₂O: nitrous oxide; D˙O₂: total body oxygen delivery; V˙O₂: total body oxygen consumption; C_(a−v)O₂: arterial to mixed venous oxygen content difference

Plasma electrolytes and osmolarity

Plasma osmolarity and plasma concentrations of sodium and potassium did not differ between protocols and were not substantially changed by any anaesthesia regimen.

Ventilatory parameters

Ventilatory parameters did not differ between protocols. Tidal volume was 195 ± 18 mL during isoflurane/N₂O, 221 ± 6 mL during isoflurane/remifentanil, and 216 ± 8 mL during xenon/remifentanil anaesthesia. Respectively, minute volume amounted to 2.4 ± 0.2, 2.6 ± 0.1 and 2.5 ± 0.1/L/min, with a respiratory rate of 13 ± 1, 12 ± 1 and 12 ± 1/min, a mean airway pressure of 13 ± 1, 14 ± 1 and 14 ± 1 mmHg, and an end-tidal carbon dioxide tension of 35 ± 1, 37 ± 1 and 36 ± 1 mmHg, during the respective anaesthesia regimen.

Discussion

The objective of this study was to determine whether xenon/remifentanil has less cardiovascular and hormonal adverse effects than isoflurane/remifentanil or isoflurane/N₂O anaesthesia. It was found that:
Xenon/remifentanil appears to reduce CO and HR to a greater extent than either isoflurane/remifentanil or isoflurane/N₂O anaesthesia.

MAP was unaffected by xenon/remifentanil anaesthesia, but decreased during isoflurane/N₂O and isoflurane/remifentanil anaesthesia.

Compared with the two isoflurane regimens, xenon/remifentanil anaesthesia produced higher plasma concentrations of adrenaline, noradrenaline and vasopressin resulting in excessively high SVR values in this group.

Systemic oxygen consumption was unaffected by isoflurane/remifentanil anaesthesia, but reduced by isoflurane/N₂O and xenon/remifentanil anaesthesia.

Haemodynamics

During isoflurane/N₂O anaesthesia we found an increase in HR which is consistent with previous studies in dogs (Picker et al. 2001), and has been associated with reduced cardiac vagal activity. When isoflurane was combined with remifentanil we found a decrease in HR, as a result of the dose-dependent bradycardic effect of remifentanil in dogs (Michelsen et al. 1996). However, bradycardia was more pronounced when remifentanil was combined with xenon rather than isoflurane (Table 1). It therefore seems reasonable to conclude that in xenon/remifentanil anesthetized dogs bradycardia cannot be attributed to remifentanil alone. Indeed, a certain degree of bradycardia has also been described during xenon anaesthesia in pigs (Vagts et al. 2004) and humans (Rossaint et al. 2003, Coburn et al. 2005).

CO decreased during all anaesthesia regimens tested in our study. The decrease in CO was most pronounced during xenon/remifentanil anaesthesia (Table 1). As SV was only moderately reduced during xenon/remifentanil anaesthesia, the reduced CO is likely to be a consequence of bradycardia.

Vascular resistance was calculated from MAP and CO. For this reason, one cannot readily conclude that the high SVR observed in the xenon/remifentanil group was a response to the decrease in CO, e.g. due to direct myocardial effects. It could likely be reflective of neuro-hormonally mediated constriction of peripheral vessels (see below) elevating left ventricular afterload and thereby impairing CO.

Hormones

Activation of the renin–angiotensin–aldosterone system can be caused either by intrarenal stimuli of renin release (renal barostat and macula densa mechanisms) or by extrarenal stimuli (renal nerves or elevated plasma adrenaline and noradrenaline concentrations) (Davis & Freeman 1976). During xenon/remifentanil anaesthesia, the renin–angiotensin system was activated in the face of unaltered arterial blood pressure. Consequently, extrarenal factors such as plasma catecholamines would seem to be the important stimuli of the renin–angiotensin system when xenon is used. Indeed, xenon anaesthesia resulted in a four-fold increase in adrenaline and a 12-fold increase in noradrenaline concentrations (Figure 2). Since remifentanil has been shown to leave catecholamine concentrations unaltered and to suppress rather than to stimulate the sympathetic nervous system (Myre et al. 2003), we think that the increase of the catecholamines can be attributed to xenon rather than to remifentanil in the xenon/remifentanil protocol.

Vasopressin increased to vasopressor concentrations under all three regimens. We assume that the relatively higher levels of vasopressin, which were observed during xenon/remifentanil anaesthesia when compared with isoflurane/N₂O or isoflurane/remifentanil anaesthesia, were most likely due to the xenon-induced adjustments of the sympathetic nervous system and release of adrenaline and noradrenaline (Figure 2). Other factors that might stimulate vasopressin release are linked either to a barostat and/or volustat mechanism that depends on left ventricular, aortic and carotid sinus receptors (Wang et al. 1988), or to changes in plasma osmolarity. None of these factors were present during the application of xenon in this study.

In summary, our results seem to suggest that the increase in SVR following xenon/remifentanil anaesthesia is a result of a neuro-hormonal compensatory response to the negative chronotropic effects of xenon. It could also be argued that the prominent increase in afterload is the cause of rather than the response to decreased CO. However, in this case one would have expected a more pronounced reduction of SV, which was only minimally affected. This might reflect a catecholamine-related positive inotropic effect to prevent a major reduction of SV in the face of increased afterload.

It was not possible to measure the effect of the various regimens used on myocardial function directly (e.g. by echocardiography). It is, however, known that xenon does not share the inhibitory effects of volatile anaesthetics on myocardial calcium channels and contractility of isolated muscle bundles (Hüneke et al. 2001, Schroth et al. 2002). Further it has not been shown to have any influence on left ventricular performance in dogs (Hettrick et al. 1998) or on fractional area change in transoesophageal echocardiography in humans (Luttropp et al. 1993).

Catecholamines during xenon anaesthesia

The increase in circulating catecholamines as encountered during xenon/remifentanil anaesthesia in our study has not previously been described. Existing studies have reported decreased or slightly increased catecholamine levels during xenon anaesthesia in pigs (Marx et al. 1997) and humans (Boomsma et al. 1990). In an acutely instrumented pig model (Vagts et al. 2004) xenon was associated with stable arterial blood pressure along with a distinct reduction in CO and intestinal perfusion. In that study, adrenaline concentrations of 3.35 nmol/L (∼615 pg/mL) and noradrenaline concentrations of 3.41 nmol/L (∼578 pg/mL) were measured in plasma when no xenon was added to a baseline intravenous anaesthesia, and no increase in catecholamines was observed upon the addition of up to 65 vol% of xenon (Vagts et al. 2004). That is, their catecholamine concentrations without* xenon were already in a range found only after an increase during xenon/remifentanil anaesthesia in our study (Figure 2). Apart from species differences, this might reflect a certain degree of stress being put on the pigs during instrumentation as compared with our dogs that have been accustomed to the experimental situation through weeks of training (Francis et al. 2004). Beyond this, xenon was used on top of an established intravenous anaesthesia with ketamine and flunitrazepam. Both ketamine and xenon do inhibit the N-methyl-D-aspartate (NMDA) receptor (de Sousa et al. 2000, Gruss et al. 2004, Hüneke et al. 2004), and by this means, ketamine is involved in the release, metabolism and reuptake of adrenaline and noradrenaline (Kienbaum et al. 2000). Therefore, the high baseline catecholamine concentrations observed in the instrumented pig model may be caused by the ketamine masking or even abolishing a xenon-related increase of catecholamine concentrations. In contrast to volatile anaesthetics, xenon has been shown to be an NMDA receptor ligand (Yamakura & Harris 2000) and to increase catecholamine release in the brain (Yoshida et al. 2001). Stimulation of noradrenergic neurons in the hypothalamus may be one mechanism contributing to the sympathotonic effects of xenon (Preckel et al. 2006). Therefore, the release of catecholamines during xenon anaesthesia in our study might be related to an NMDA receptor-mediated effect in a ketamine-like fashion. Our study was not however designed to elucidate in detail by what means xenon leads to the increase of plasma catecholamines.

Depth of anaesthesia

It might be argued that high plasma catecholamine concentrations during xenon/remifentanil anaesthesia could reflect inadequate depth of anaesthesia. Indeed, our vol% dose of administered xenon was 63 ± 1%, whereas the MAC of xenon is actually 120% in dogs (Eger et al. 1965a). However, had the depth of anaesthesia been inadequate one would have expected to see a certain degree of stress response with its consequent pronounced activation of the renin–angiotensin system and tachycardia. This was not the case, however. To test the depth of anaesthesia, a tail-clamping technique was used. The tail-clamp (Eger et al. 1965a) is the equivalent of a skin incision in humans and is a recognized ‘golden standard’ in the assessment of MAC. MAC is defined as the anaesthetic concentration required to prevent 50% of patients from responding to a painful stimulus (skin incision, tail-clamp) with gross purposeful movements. The tail-clamp was firmly placed for 5 min immediately after induction and then at every 20 min interval during anaesthesia. We did not observe an increase in HR or blood pressure, withdrawal reactions, movement of the tail or limbs, wide pupils or the return of the eyelash reflex during any of the cases. The tail-clamp results were negative for all anaesthetic methods. Electrophysiological brain monitoring with bispectral index (BIS) has been used to monitor the degree of CNS depression in the anaesthetized dog (Greene et al. 2003) but it does not correlate with haemodynamic changes upon nociceptive stimuli (Nakayama et al. 2003, Carrasco-Jimenez et al. 2004) or MAC values and consequently cannot replace the tail-clamp in the assessment of adequate depth of anaesthesia.

Oxygen metabolism

Due to both the reduction in CO and the depth of anaesthesia, oxygen delivery declined during all protocols. During xenon/remifentanil anaesthesia oxygen consumption decreased along with a prominent decrease (61%) in CO. As a consequence, peripheral oxygen extraction, as expressed by c_(a-v)O₂, increased and was greater than during both isoflurane protocols (Table 4)

In contrast, Picker et al. (2002) have reported that xenon, when added to an established isoflurane anaesthesia, induces an increase in oxygen consumption without significantly altering CO. However, as isoflurane was used as an anaesthetic in combination with xenon their results are not comparable with our study.

Regarding metabolic changes (Table 3), base excess was not significantly different between protocols. Mixed venous oxygen saturation remained unchanged during isoflurane/N₂O, where CO was reduced least, but decreased during isoflurane/remifentanil and xenon/remifentanil anaesthesia where CO was impaired most.

In summary, in our experimental dog model, xenon/remifentanil does not reduce anaesthesia-related cardiovascular and hormonal effects but actually produces its own unique set of haemodynamic and hormonal disturbances. Specifically, xenon/remifentanil does not alter MAP but nevertheless reduces CO to a greater extent than isoflurane-based anaesthesia. This is attributable to bradycardia along with extraordinarily high SVR and an exaggerated release of vasopressor hormones.

While xenon is well reputed in numerous investigations on haemodynamics that emphasize its haemodynamic neutrality, we demonstrated that the maintenance of MAP alone in the context of examining cardiovascular physiology is almost meaningless unless hormonal alterations and other haemodynamic parameters are taken into account.

These findings should be considered in the planning, performance and interpretation of investigations on cardiovascular and hormonal physiology in anaesthetized dogs and humans. They should encourage further research with emphasis on cardiovascular hormones during xenon anaesthesia in patients to evaluate in more detail whether xenon exerts potentially adverse haemodynamic or hormonal effects in humans.

	Awake	Anaesthesia
Heart rate, beats/min
Isoflurane/N₂O	88 ± 3	98 ± 3^†
Isoflurane/remifentanil	77 ± 5	54 ± 2*^†
Xenon/remifentanil	86 ± 4	40 ± 3*
Cardiac output, L/min
Isoflurane/N₂O	2.2 ± 0.1	1.6 ± 0.1*^†
Isoflurane/remifentanil	2.3 ± 0.2	1.2 ± 0.1*^†
Xenon/remifentanil	2.3 ± 0.2	0.9 ± 0.1*
Stroke volume, mL
Isoflurane/N₂O	26 ± 2	17 ± 1*
Isoflurane/remifentanil	29 ± 2	23 ± 2*
Xenon/remifentanil	27 ± 2	23 ± 2*
MAP, mmHg
Isoflurane/N₂O	86 ± 2	65 ± 2*^†
Isoflurane/remifentanil	95 ± 2	67 ± 3*^†
Xenon/remifentanil	96 ± 4	85 ± 6
Systemic vascular resistance, dyn seconds/cm⁵
Isoflurane/N₂O	3025 ± 211	3148 ± 121^†
Isoflurane/remifentanil	3387 ± 309	4443 ± 369*^†
Xenon/remifentanil	3282 ± 281	7231 ± 803*
Mean pulmonary artery pressure, mmHg
Isoflurane/N₂O	12 ± 1	13 ± 1^†
Isoflurane/remifentanil	12 ± 1	11 ± 1^†
Xenon/remifentanil	12 ± 1	16 ± 1*
Pulmonary vascular resistance, dyn seconds/cm⁵
Isoflurane/N₂O	350 ± 20	452 ± 32*^†
Isoflurane/remifentanil	376 ± 52	557 ± 24*
Xenon/remifentanil	365 ± 54	652 ± 55*
Central venous pressure, cmH₂O
Isoflurane/N₂O	2 ± 0.2	2 ± 0.2^†
Isoflurane/remifentanil	1 ± 1	3 ± 1*^†
Xenon/remifentanil	3 ± 1	8 ± 1*
Pulmonary capillary wedge pressure, cmH₂O
Isoflurane/N₂O	2 ± 0.3	4 ± 0.4*^†
Isoflurane/remifentanil	1 ± 0.3	3 ± 0.4*^†
Xenon/remifentanil	2 ± 0.7	9 ± 0.9*

	Awake	Anaesthesia
Renin activity, ngAngI/mL/h
Isoflurane/N₂O	3.4 ± 0.6	24.9 ± 2.9*
Isoflurane/remifentanil	3.1 ± 0.6	31.8 ± 5.7*
Xenon/remifentanil	3.7 ± 0.9	20.2 ± 3.2*
Aldosterone, pg/mL
Isoflurane/N₂O	78 ± 14	672 ± 52*
Isoflurane/remifentanil	100 ± 22	1114 ± 57*^†
Xenon/remifentanil	89 ± 20	700 ± 140*
Endothelin-1, pg/mL
Isoflurane/N₂O	1.0 ± 0.1	1.1 ± 0.1
Isoflurane/remifentanil	1.0 ± 0.2	1.1 ± 0.2
Xenon/remifentanil	0.9 ± 0.1	1.2 ± 0.1*
Atrial natriuretic peptide, pg/mL
Isoflurane/N₂O	60 ± 8	42 ± 7*^†
Isoflurane/remifentanil	68 ± 7	73 ± 7
Xenon/remifentanil	57 ± 6	63 ± 3

	Awake	Anaesthesia
F_iO₂
Isoflurane/N₂O	Ambient air	0.33 ± 0.01^†
Isoflurane/remifentanil	Ambient air	0.26 ± 0.01^†
Xenon/remifentanil	Ambient air	0.29 ± 0.01
P_aO₂, mmHg
Isoflurane/N₂O	95 ± 1	181 ± 3*^†
Isoflurane/remifentanil	99 ± 2	138 ± 15*
Xenon/remifentanil	98 ± 1	143 ± 6*
P_vO₂, mmHg
Isoflurane/N₂O	44 ± 1	47 ± 1^†
Isoflurane/remifentanil	48 ± 2	38 ± 1*
Xenon/remifentanil	46 ± 2	39 ± 1*
P_aCO₂, mmHg
Isoflurane/N₂O	35 ± 1	35 ± 1
Isoflurane/remifentanil	35 ± 1	38 ± 1
Xenon/remifentanil	37 ± 1	37 ± 1
pH_a
Isoflurane/N₂O	7.39 ± 0.01	7.38 ± 0.01
Isoflurane/remifentanil	7.39 ± 0.01	7.38 ± 0.01
Xenon/remifentanil	7.39 ± 0.01	7.35 ± 0.01*
BE_a, mmol/L
Isoflurane/N₂O	−2.2 ± 0.7	−4.2 ± 0.3*
Isoflurane/remifentanil	−2.4 ± 0.5	−3.7 ± 0.5*
Xenon/remifentanil	−2.5 ± 0.5	−5.0 ± 0.6*
S_aO₂, %
Isoflurane/N₂O	98 ± 0.2	100 ± 0.1*
Isoflurane/remifentanil	99 ± 0.2	100 ± 0.1
Xenon/remifentanil	99 ± 0.4	100 ± 0.2
S_vO₂, %
Isoflurane/N₂O	80 ± 3	82 ± 1^†
Isoflurane/remifentanil	83 ± 2	69 ± 2*
Xenon/remifentanil	81 ± 2	67 ± 2*

	Awake	Anaesthesia
D˙O₂, mL/min
Isoflurane/N₂O	381 ± 39	238 ± 22*
Isoflurane/remifentanil	412 ± 52	196 ± 18*
Xenon/remifentanil	426 ± 43	179 ± 14*
V˙O₂, mL/min
Isoflurane/N₂O	68 ± 2	48 ± 4*
Isoflurane/remifentanil	68 ± 5	61 ± 3
Xenon/remifentanil	76 ± 3	58 ± 3*
C_(a−v)O₂, mL/dL
Isoflurane/N₂O	3.1 ± 0.3	2.9 ± 0.3^†
Isoflurane/remifentanil	2.8 ± 0.3	5.2 ± 0.2*^†
Xenon/remifentanil	3.4 ± 0.2	6.7 ± 0.4*

Footnotes

Acknowledgements

We thank Rainer Mohnhaupt (Research Engineer), Daniela Bayerl and Birgit Brandt (Research Laboratory Technicians) for their valuable assistance during the experiments, and Martin McGuill for editorial assistance. The PhysioFlex™ ventilator was generously supplied by Dräger Medical AG, Lübeck, Germany, and xenon was provided by Air Liquide Deutschland GmbH, Germany.

References

Boomsma

, Rupreht

, Man in 't Veld

, de Jong

, Dzoljic

, Lachmann

(1990) Haemodynamic and neurohumoral effects of xenon anaesthesia. A comparison with nitrous oxide. Anaesthesia 45, 273–8

Burchardi

, Kaczmarczyk

(1994) The effect of anaesthesia on renal function. European Journal of Anaesthesiology 11, 163–8

Carrasco-Jimenez

, Martin Cancho

, Lima

, Crisostomo

, Uson-Gargallo

, Ezquerra

(2004) Relationships between a proprietary index, bispectral index, and hemodynamic variables as a means for evaluating depth of anesthesia in dogs anesthetized with sevoflurane. American Journal of Veterinary Research 65, 1128–35

Coburn

, Kunitz

, Baumert

, (2005) Randomized controlled trial of the haemodynamic and recovery effects of xenon or propofol anaesthesia. British Journal of Anaesthesia 94, 198–202

Cullen

(1986) Anesthetic depth and MAC. In: Anesthesia ( Miller

, ed). New York: Churchill Livingstone, 553–80

Davis

, Freeman

(1976) Mechanisms regulating renin release. Physiological Reviews 56, 1–56

de Sousa

, Dickinson

, Lieb

, Franks

(2000) Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon. Anesthesiology 92, 1055–66

Eger

II , Brandstater

, Saidman

, Regan

, Severinghaus

, Munson

(1965a) Equipotent alveolar concentrations of methoxyflurane, halothane, diethyl ether, fluroxene, cyclopropane, xenon and nitrous oxide in the dog. Anesthesiology 26, 771–7

Eger

II , Saidman

, Brandstater

(1965b) Minimum alveolar anesthetic concentration: a standard of anesthetic potency. Anesthesiology 26, 756–63

10.

Francis

, Höhne

, Kaczmarczyk

, Boemke

(2004) Effect of angiotensin II and endothelin-1 receptor blockade on the haemodynamic and hormonal changes after acute blood loss and after retransfusion in conscious dogs. Acta Physiologica Scandinavica 180, 319–28

11.

Greene

, Tranquilli

, Benson

, Grimm

(2003) Effect of medetomidine administration on bispectral index measurements in dogs during anesthesia with isoflurane. American Journal of Veterinary Research 64, 316–20

12.

Gruss

, Bushell

, Bright

, Lieb

, Mathie

, Franks

(2004) Two-pore-domain cK+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Molecular Pharmacology 65, 443–52

13.

Hettrick

, Pagel

, Warltier

(1996) Desflurane, sevoflurane, and isoflurane impair canine left ventricular-arterial coupling and mechanical efficiency. Anesthesiology 85, 403–13

14.

Hettrick

, Pagel

, Kersten

, (1998) Cardiovascular effects of xenon in isoflurane-anesthetized dogs with dilated cardiomyopathy. Anesthesiology 89, 1166–73

15.

Höhne

, Francis

RCE

, Kaczmarczyk

, Boemke

(2002) Haemodynamic and hormonal changes during haemorrhage in conscious dogs treated with an endothelin-A receptor antagonist. Clinical Science 103(suppl. 48), 336–339S

16.

Hüneke

, Jungling

, Skasa

, Rossaint

, Luckhoff

(2001) Effects of the anesthetic gases xenon, halothane, and isoflurane on calcium and potassium currents in human atrial cardiomyocytes. Anesthesiology 95, 999–1006

17.

Hüneke

, Fassl

, Rossaint

, Luckhoff

(2004) Effects of volatile anesthetics on cardiac ion channels. Acta Anaesthesiologica Scandinavica 48, 547–61

18.

Institute of Laboratory Animal Research, Commission on Life Sciences, National Research Council (1996) Guide for the Care and Use of Laboratory Animals. 7th edn. Washington, DC: The National Academies Press

19.

Ishiguro

(2001) Cardiovascular effects of xenon. International Anesthesiology Clinics 39, 77–84

20.

Ishiguro

, Goto

, Nakata

, Terui

, Niimi

, Morita

(2000) Effect of xenon on autonomic cardiovascular control – comparison with isoflurane and nitrous oxide. Journal of Clinical Anesthesia 12, 196–201

21.

Jansen

JRC

, Schreuder

, Settels

, Kloek

, Versprille

(1990) An adequate strategy for the thermodilution technique in patients during mechanical ventilation. Intensive Care Medicine 16, 422–5

22.

Kienbaum

, Heuter

, Michel

, Peters

(2000) Racemic ketamine decreases muscle sympathetic activity but maintains the neural response to hypotensive challenges in humans. Anesthesiology 92, 94–101

23.

Lane

, Nahrwold

, Tait

, Taylor-Busch

, Cohen

, Beaudoin

(1980) Anesthetics as teratogens: nitrous oxide is fetotoxic, xenon is not. Science 210, 899–901

24.

Lang

, Kapila

, Shlugman

, Hoke

, Sebel

, Glass

(1996) Reduction of isoflurane minimal alveolar concentration by remifentanil. Anesthesiology 85, 721–8

25.

Luttropp

, Romner

, Perhag

, Eskilsson

, Fredriksen

, Werner

(1993) Left ventricular performance and cerebral haemodynamics during xenon anaesthesia. A transoesophageal echocardiography and transcranial Doppler sonography study. Anaesthesia 48, 1045–9

26.

Lynch

III , Baum

, Tenbrinck

(2000) Xenon anesthesia. Anesthesiology 92, 865–8

27.

Marx

, Froeba

, Wagner

, Baeder

, Goertz

, Georgieff

(1997) Effects on haemodynamics and catecholamine release of xenon anaesthesia compared with total i.v. anaesthesia in the pig. British Journal of Anaesthesia 78, 326–7

28.

Michelsen

, Salmenpera

, Hug

Jr , Szlam

, VanderMeer

(1996) Anesthetic potency of remifentanil in dogs. Anesthesiology 84, 865–72

29.

Myre

, Raeder

, Rostrup

, Buanes

, Stokland

(2003) Catecholamine release during laparoscopic fundoplication with high and low doses of remifentanil. Acta Anaesthesiologica Scandinavica 47, 267–73

30.

Nakayama

, Kanaya

, Edanaga

, Namiki

(2003) Hemodynamic and bispectral index responses to tracheal intubation during isoflurane or sevoflurane anesthesia. Journal of Anesthesia 17, 223–6

31.

Picker

, Scheeren

, Arndt

(2001) Inhalation anaesthetics increase heart rate by decreasing cardiac vagal activity in dogs. British Journal of Anaesthesia 87, 748–54

32.

Picker

, Schindler

, Schwarte

, (2002) Xenon increases total body oxygen consumption during isoflurane anaesthesia in dogs. British Journal of Anaesthesia 88, 546–54

33.

Preckel

, Mullenheim

, Hoff

, (2004) Haemodynamic changes during halothane, sevoflurane and desflurane anaesthesia in dogs before and after the induction of severe heart failure. European Journal of Anaesthesiology 21, 797–806

34.

Preckel

, Weber

, Sanders

, Maze

, Schlack

(2006) Molecular mechanisms transducing the anesthetic, analgesic, and organ-protective actions of xenon. Anesthesiology 105, 187–97

35.

Rossaint

, Reyle-Hahn

, Schulte Am Esch

, (2003) Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery. Anesthesiology 98, 6–13

36.

Schaffer

(1986) Modified sequentially rejective multiple test procedures. Journal of the American Statistical Association 81, 826–31

37.

Schroth

, Schotten

, Alkanoglu

, Reyle-Hahn

, Hanrath

, Rossaint

(2002) Xenon does not impair the responsiveness of cardiac muscle bundles to positive inotropic and chronotropic stimulation. Anesthesiology 96, 422–7

38.

Vagts

, Hecker

, Iber

, (2004) Effects of xenon anaesthesia on intestinal oxygenation in acutely instrumented pigs. British Journal of Anaesthesia 93, 833–41

39.

Wang

, Flora-Ginter

, Leadley

Jr , Goetz

(1988) Ventricular receptors stimulate vasopressin release during hemorrhage. American Journal of Physiology 254, R204–11

40.

Yamakura

, Harris

(2000) Effects of gaseous anesthetics nitrous oxide and xenon on ligand-gated ion channels. Comparison with isoflurane and ethanol. Anesthesiology 93, 1095–101

41.

Yoshida

, Kushikata

, Kubota

, Hirota

, Ishihara

, Matsuki

(2001) Xenon inhalation increases norepinephrine release from the anterior and posterior hypothalamus in rats. Canadian Journal of Anaesthesia 48, 651–5

The haemodynamic and catecholamine response to xenon/remifentanil anaesthesia in Beagle dogs

Abstract

Keywords

Materials and methods

Animal maintenance and dietary regimen

Experimental protocols

Isoflurane/N2O

Isoflurane/remifentanil

Xenon/remifentanil

Measurements and calculations

Statistical analysis

Results

Haemodynamics

Plasma hormones

Blood gases and oxygen consumption

Plasma electrolytes and osmolarity

Ventilatory parameters

Discussion

Haemodynamics

Hormones

Catecholamines during xenon anaesthesia

Depth of anaesthesia

Oxygen metabolism

Footnotes

Acknowledgements

References

Isoflurane/N₂O