1Centre for Equine Studies, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK. 2Kansas State University, Manhattan, Kansas, USA. 3Centre for Small Animal Studies, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK. 4Department of Veterinary Clinical Studies, R(D)SVS, Edinburgh, UK.*Corresponding author
Accepted for publication: August 29, 2000
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Abstract |
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Br J Anaesth 2001; 86: 12730
Keywords: horse; anaesthesia; pharmacology, nitric oxide; anaesthetics volatile, halothane
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Introduction |
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Methods and results |
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Measurements of pulmonary artery pressure (PPA) were made using a strain-gauge transducer mounted on the tip of a 150 cm, 8F, woven Dacron catheter (Gaeltec, Dunvegan, Isle of Skye, UK) interfaced to a pressure amplifier (Model 13461552; Gould, Essex, UK). The catheter was introduced via an 8F arterial sheath introducer (Haemaquet-Steri Lock; Bard, Crawley, UK) into the right jugular vein. Cardiac output (Q²) was measured using transoesophageal Doppler echocardiography. Arterial blood oxygen (PaO2) and carbon dioxide (PaCO2) tensions were measured at 37°C with a blood gas analyser (model 248; Chiron Diagnostics, Essex, UK).
Respiratory airflow was measured with a Fleisch No. 3 heated pneumotachometer connected to a differential pressure transducer (DP4114; Validyne, Northridge, CA, USA). The pneumotachometer was calibrated with a known volume (7 litres) from a calibrated volume syringe (Series 4900; Hans Rudolph, Kansas City, KA, USA). Respired gases (oxygen, nitrogen, carbon dioxide and halothane) were measured continuously with a respiratory mass spectrometer (MGA200; Morgan Medical Ltd, Rainham, UK). The mass spectrometer was calibrated with two certified gas mixtures representing the range to be encountered during the studies (BOC Speciality Gases, Guildford, UK). The sampling capillary was inserted into the circuit distal to the pneumotachometer to sample both inspired and expired gases.
Concentrations of NO (p.p.b.) in the inspired and expired limbs of the circuit approximately 15 cm on each side of the Y-piece were measured with a dedicated chemiluminescence analyser (270B; Sievers Instruments, Boulder, CO, USA). Measurements of both inhaled and exhaled NO were made over 30 s during periods of regular breathing to reduce the effect of variations throughout each breath in NO concentration and the inherent variation of the analyser, which in the HA procedure was operating near the manufacturers reported lower limit of sensitivity (5 p.p.b.). This approach was considered preferable to making single point measurements of NO concentration. As the gas in the expired limb continues to be sampled by the NO analyser during the subsequent period of inspiration, this approach could potentially bias the average exhaled NO concentration according to the NO concentration in the last portion of gas exhaled. In order to reduce this error, measurements were made only during periods of regular breathing, without periods of apnoea between breaths, which would have prolonged the period in which the end-tidal NO continued to be sampled. In addition, the exhaled NO concentration varied minimally throughout exhalation. Net NO production was estimated by subtracting inspired NO concentration from expired NO concentration. Before each measurement of inspired and expired NO, a two-point calibration was performed with zero (100% nitrogen) and mixtures made by volume dilution of a certified NO standard mixture (400 p.p.b.; BOC Speciality Gases).
To determine that halothane did not affect the NO analyser, the anaesthetic system was set up without being connected to a horse and the connection to the tracheal tube was capped. The system was filled and flushed with oxygen and, once the oxygen concentration was above 98%, the flow rate was adjusted to 10 litre min1. Nitric oxide from a cylinder at 1000 p.p.m. (BOC Speciality Gases) was metered into the circuit to achieve a concentration at the Y-piece of 5 p.p.m., as determined by the NO analyser. Halothane was then added to the circuit to a maximum concentration of 3%, as determined by a calibrated piezo-electric agent monitor (Lamtec 605; Pneupac, Luton, UK), with the sample line positioned at the Y-piece of the breathing circuit.
In order to express respired gas volumes according to BTPS (body temperature and pressure, saturated) convention, gas was drawn continuously from the inspiratory limb of the circuit by a vacuum pump (flow rate <3 litre min1) across a combined temperature and humidity sensor (HMP35B; Vaisala, Cambridge, UK). A second probe in the operating theatre recorded ambient temperature and humidity.
The voltage signals from the pressure amplifier, pneumotachometer and NO analyser were digitized at 500 Hz and analysed with a commercial data acquisition and analysis system (Po-Ne-Mah; Linton Instrumentation, Diss, UK). Measurements of diastolic (PPA DIA), systolic (PPA SYS) and mean pulmonary artery pressure (PPA MEAN), respiratory minute ventilation (V²E) and net NO production were made at 40 and 60 min of anaesthesia in both groups. Effects of time and treatment were investigated using analysis of variance and Tukeys test. Where data were not normally distributed (net exhaled NO concentration, V²NO, PaO2 and Q²), they were transformed by conversion to the natural logarithm before statistical analysis.
Net exhaled NO concentration, tidal volume, respiratory minute ventilation, NO production rate, fractional inspired oxygen, end-tidal carbon dioxide, partial pressures of oxygen and carbon dioxide in arterial blood, cardiac output and pulmonary artery pressures after 40 and 60 min of HA and IV anaesthesia are shown in Table 1. There was no significant within-group difference between the 40 and 60 min time points for any of the measurements with either technique.
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Comment |
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Reduced airway NO production has also been reported in association with increased inspired carbon dioxide, but in the present study there was no significant difference in arterial carbon dioxide between procedures. It has also been suggested that the degree of lung distension may effect NO production in anaesthetized rabbits8 and exercising horses.1 Tidal volume was not different between anaesthetic regimens, although minute ventilation was significantly higher with the IV procedure. A change in functional residual capacity could have occurred, but there is no reason to expect that this would have been different between procedures. Measured exhaled NO could have been reduced if removal of NO by the lower airways was enhanced, although how this might be mediated is unclear.
NO has been shown to be involved in the regulation of pulmonary vascular tone in both systemic and pulmonary circulations in many species, including the horse.2 3 A consequence of reduced NO production or increased removal during anaesthesia might therefore be expected to be manifested as an increase in pulmonary arterial pressure. In the present study, mean pulmonary artery pressure was greater in the HA group than in the IV group. Other mechanisms that could have resulted in a higher mean pulmonary artery pressure include increased cardiac output and arterial carbon dioxide tension, although in the present study these were not different between procedures. Alternatively, the lower pulmonary pressures in the IV procedure could have been due to the intravenous drug mixture per se, but romifidine, an 2-adrenoreceptor agonist, usually increases systemic vascular resistance and pulmonary artery pressures in conscious horses. In addition, with the IV procedure mean pulmonary artery pressures were similar to those in conscious, unsedated horses at rest.
In the present study we have shown that NO production is reduced in horses anaesthetized with halothane compared with an intravenous regimen, and that this is associated with an increase in mean pulmonary artery pressure. We have also shown in a separate study that administration of exogenous inhaled NO (10 p.p.m.) did not reduce pulmonary artery pressure during halothane anaesthesia.9 Therefore, the present study supports the hypothesis that halothane causes in vivo suppression of NOS. However, failure of exogenous inhaled NO to reduce pulmonary artery pressure during halothane anaesthesia implies either that NO is not important for the regulation of pulmonary vascular tone under these conditions or that there is inhibition of the action of NO, possibly through interference with cGMP-mediated relaxation.10 In conclusion, it is possible that the increased mean pulmonary artery pressure in these horses during halothane anaesthesia may be linked to the observed differences in NO production.
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Acknowledgements |
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References |
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