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Biomedical subjects

Göran Hedenstierna

Publications and source records attributed to Göran Hedenstierna.

At least 19 recordsLinked to original sources
PubMed2007

Nitric oxide up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis.

OBJECTIVES: Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocorticoids inhibit similar transcription factors. We hypothesized that there may be an interaction between nitric oxide and glucocorticoids, with the potential to enhance the anti-inflammatory effect when administered simultaneously. DESIGN: Prospective, randomized, controlled study. SETTING: Animal research laboratory. SUBJECTS: A total of 45 anesthetized and mechanically ventilated pigs. INTERVENTIONS: Lung and systemic injury was induced by intravenous infusion of endotoxin (lipopolysaccharide) for 6 hrs. After 2.5 hrs, one group received 3.5 mg/kg hydrocortisone, another group inhaled nitric oxide (30 ppm), and still another group received both steroid and nitric oxide. Control groups of healthy and endotoxin-exposed piglets were also studied. MEASUREMENTS AND MAIN RESULTS: Central hemodynamics and gas exchange were measured. Detection of the glucocorticoid receptor and inflammatory markers in lung, liver, and kidney tissue were made by immunohistochemistry, and morphology was studied with light microscopy. Endotoxin infusion markedly reduced glucocorticoid receptor expression in lung, liver, and kidney and up-regulated activator protein-1 and the inflammatory markers nuclear factor-kappaB and tumor necrosis factor-alpha. When administered separately, steroids and nitric oxide had modest effect on the inflammatory response. However, nitric oxide up-regulated the glucocorticoid receptor expression. Simultaneous administration of steroids and nitric oxide attenuated the inflammatory response and almost preserved or restored normal histology of both lung and systemic organs. When the glucocorticoid receptor was blocked by a receptor antagonist (mifepristone, 600 mg) and inhaled nitric oxide was subsequently administered, no increase in the expression of the glucocorticoid receptor was seen. CONCLUSION: We suggest that up-regulation of glucocorticoid receptor expression by nitric oxide made steroid therapy more effective.

Administration, Inhalation↗
PubMed2007

Use of dynamic compliance for open lung positive end-expiratory pressure titration in an experimental study.

OBJECTIVE: We tested whether the continuous monitoring of dynamic compliance could become a useful bedside tool for detecting the beginning of collapse of a fully recruited lung. DESIGN: Prospective laboratory animal investigation. SETTING: Clinical physiology research laboratory, University of Uppsala, Sweden. SUBJECTS: Eight pigs submitted to repeated lung lavages. INTERVENTIONS: Lung recruitment maneuver, the effect of which was confirmed by predefined oxygenation, lung mechanics, and computed tomography scan criteria, was followed by a positive end-expiratory pressure (PEEP) reduction trial in a volume control mode with a tidal volume of 6 mL/kg. Every 10 mins, PEEP was reduced in steps of 2 cm H2O starting from 24 cm H2O. During PEEP reduction, lung collapse was defined by the maximum dynamic compliance value after which a first measurable decrease occurred. Open lung PEEP according to dynamic compliance was then defined as the level of PEEP before the point of collapse. This value was compared with oxygenation (Pao2) and CT scans. MEASUREMENTS AND MAIN RESULTS: Pao2 and dynamic compliance were monitored continuously, whereas computed tomography scans were obtained at the end of each pressure step. Collapse defined by dynamic compliance occurred at a PEEP of 14 cm H2O. This level coincided with the oxygenation-based collapse point when also shunt started to increase and occurred one step before the percentage of nonaerated tissue on the computed tomography exceeded 5%. Open lung PEEP was thus at 16 cm H2O, the level at which oxygenation and computed tomography scan confirmed a fully open, not yet collapsed lung condition. CONCLUSIONS: In this experimental model, the continuous monitoring of dynamic compliance identified the beginning of collapse after lung recruitment. These findings were confirmed by oxygenation and computed tomography scans. This method might become a valuable bedside tool for identifying the level of PEEP that prevents end-expiratory collapse.

Airway Resistance↗
PubMed2007

Lung aeration during sleep.

BACKGROUND: During sleep, ventilation and functional residual capacity (FRC) decrease slightly. This study addresses regional lung aeration during wakefulness and sleep. METHODS: Ten healthy subjects underwent spirometry awake and with polysomnography, including pulse oximetry, and also CT when awake and during sleep. Lung aeration in different lung regions was analyzed. Another three subjects were studied awake to develop a protocol for dynamic CT scanning during breathing. RESULTS: Aeration in the dorsal, dependent lung region decreased from a mean of 1.14 +/- 0.34 mL (+/- SD) of gas per gram of lung tissue during wakefulness to 1.04 +/- 0.29 mL/g during non-rapid eye movement (NREM) sleep (- 9%) [p = 0.034]. In contrast, aeration increased in the most ventral, nondependent lung region, from 3.52 +/- 0.77 to 3.73 +/- 0.83 mL/g (+ 6%) [p = 0.007]. In one subject studied during rapid eye movement (REM) sleep, aeration decreased from 0.84 to 0.65 mL/g (- 23%). The fall in dorsal lung aeration during sleep correlated to awake FRC (R(2) = 0.60; p = 0.008). Airway closure, measured awake, occurred near and sometimes above the FRC level. Ventilation tended to be larger in dependent, dorsal lung regions, both awake and during sleep (upper region vs lower region, 3.8% vs 4.9% awake, p = 0.16, and 4.5% vs 5.5% asleep, p = 0.09, respectively). CONCLUSIONS: Aeration is reduced in dependent lung regions and increased in ventral regions during NREM and REM sleep. Ventilation was more uniformly distributed between upper and lower lung regions than has previously been reported in awake, upright subjects. Reduced respiratory muscle tone and airway closure are likely causative factors.

Adult↗
PubMed2006

Monitoring dead space during recruitment and PEEP titration in an experimental model.

OBJECTIVE: To test the usefulness of dead space for determining open-lung PEEP, the lowest PEEP that prevents lung collapse after a lung recruitment maneuver. DESIGN: Prospective animal study. SETTING: Department of Clinical Physiology, University of Uppsala, Sweden. SUBJECTS: Eight lung-lavaged pigs. INTERVENTIONS: Animals were ventilated using constant flow mode with VT of 6ml/kg, respiratory rate of 30bpm, inspiratory-to-expiratory ratio of 1:2, and FiO(2) of 1. Baseline measurements were performed at 6cmH(2)O of PEEP. PEEP was increased in steps of 6cmH(2)O from 6 to 24cmH(2)O. Recruitment maneuver was achieved within 2min at pressure levels of 60/30cmH(2)O for Peak/PEEP. PEEP was decreased from 24 to 6cmH(2)O in steps of 2cmH(2)O and then to 0cmH(2)O. Each PEEP step was maintained for 10min. MEASUREMENTS AND RESULTS: Alveolar dead space (VD(alv)), the ratio of alveolar dead space to alveolar tidal volume (VD(alv)/VT(alv)), and the arterial to end-tidal PCO(2) difference (Pa-ET: CO(2)) showed a good correlation with PaO(2), normally aerated areas, and non-aerated CT areas in all animals (minimum-maximum r(2)=0.83-0.99; p<0.01). Lung collapse (non-aerated tissue>5%) started at 12[Symbol: see text]cmH(2)O PEEP; hence, open-lung PEEP was established at 14cmH(2)O. The receiver operating characteristics curve demonstrated a high specificity and sensitivity of VD(alv) (0.89 and 0.90), VD(alv)/VT(alv) (0.82 and 1.00), and Pa-ET: CO(2) (0.93 and 0.95) for detecting lung collapse. CONCLUSIONS: Monitoring of dead space was useful for detecting lung collapse and for establishing open-lung PEEP after a recruitment maneuver.

Animals↗
PubMed2006

Central hemodynamics during lung recruitment maneuvers at hypovolemia, normovolemia and hypervolemia. A study by echocardiography and continuous pulmonary artery flow measurements in lung-injured pigs.

OBJECTIVE: The impact of lung-recruitment maneuvers on heart function at different volemic levels has not been studied in detail. We therefore investigated the effect on central hemodynamics of lung recruitment maneuvers at hypovolemia, normovolemia and hypervolemia in experimental lung injury. DESIGN: Randomized, controlled, cross-over experimental study. SETTING: Animal laboratory at a university hospital. PARTICIPANTS: Eleven anesthetized and lung-lavaged pigs. INTERVENTION: The animals were randomized to 10-s lung recruitment maneuvers followed by 30-s maneuvers (40 cm H(2)O airway pressure) or vice versa, performed under hypovolemia, normovolemia and hypervolemia. MEASUREMENTS AND MAIN RESULTS: Left-ventricular end-diastolic diameter and cardiac output were measured before, during, and 1 min and 5 min after the lung recruitment maneuver and left-ventricular eccentricity index was calculated for before and during the maneuver. Cardiac output and left-ventricular end-diastolic diameter (within parentheses) decreased significantly during both the 10-s and 30-s lung recruitment maneuvers at hypovolemia, by a mean of 89% (35) and 92% (33), at normovolemia by 75% (33) and 86% (32), and at hypervolemia by 56% (32) and 64% (43), respectively. At hypovolemia, cardiac output was increased above baseline 1-5 min following the 30-s maneuver. Left-ventricular eccentricity index increased significantly during the maneuver, indicating right ventricular dysfunction. CONCLUSIONS: In this animal lung injury model, lung recruitment maneuvers significantly decreased left-ventricular end-diastolic volume and cardiac output at hypovolemia. Hypervolemia did partly counteract this compromise. In addition, a marked right-ventricular dysfunction during the maneuver was found.

Animals↗
PubMed2006

Abdominal lymph flow in an endotoxin sepsis model: influence of spontaneous breathing and mechanical ventilation.

OBJECTIVE: Lymph flow from the abdomen was investigated in a sepsis model. We also compared the effect on thoracic duct lymph flow of mechanical ventilation with different levels of positive end-expiratory pressure (PEEP) and spontaneous breathing with continuous positive airway pressure (CPAP). DESIGN: Experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Thirty-two pigs. INTERVENTIONS: Animals were anesthetized. In study 1 (n = 18), an ultrasonic flow probe was put around the intact thoracic duct just caudal to the diaphragm, and animals were randomized to receive mechanical ventilation with a PEEP of 5 cm H2O or 15 cm H2O or breathed spontaneously in CPAP with a PEEP of 5 cm H2O. In study 2 (n = 6), the thoracic duct was cannulated and the cannula externalized through the abdominal wall for lymph collection; animals were then ventilated as in study 1. In all animals, endotoxin was infused at 15 microg/kg/hr for 2.5 hrs and then continued at 5 microg/kg/hr. In study 3, healthy (n = 4) and endotoxin-exposed (n = 4) pigs had intra-abdominal pressure increased to 27 cm H2O for 2 hrs by pneumoperitoneum. Lymph flow was measured as in study 1. MEASUREMENTS AND MAIN RESULTS: Lymph flow (mean +/- SE) was 2.5 +/- 0.4 mL/min at baseline and increased to 3.9 +/- 0.8 mL/min after 90 mins and 6.3 +/- 1.6 mL/min after 150 mins (p < .005) of endotoxin exposure. PEEP 15 cm H2O decreased lymph flow in pigs with intact thoracic duct (flow probe recording) and in pigs with cannulated lymph duct when drained against the central venous pressure. However, when drained against atmospheric pressure, PEEP increased flow. Spontaneous breathing increased flow both in intact and in cannulated animals. CONCLUSIONS: Endotoxin increases lymph flow from the abdomen. Mechanical ventilation with high PEEP impedes lymph drainage and could increase lymph production. Spontaneous breathing increases flow and improves drainage of abdominal edema.

Abdomen↗
PubMed2006

Acoustic effects of positive end-expiratory pressure on normal lung sounds in mechanically ventilated pigs.

Computerized lung sounds analysis offers a new technique to monitor regional ventilation during spontaneous breathing. The purpose of the present study was to assess the acoustic behaviour of the respiratory system in healthy pigs during mechanical ventilation when a positive end-expiratory pressure (PEEP) is applied. Lung sounds were recorded during mechanical ventilation and different PEEP levels of 0, 5, 10, 15 and 20 cm H(2)O were applied. The increase in end-expiratory lung volume (EELV) related to the PEEP application was also measured and the correlation between changes in EELV (DeltaEELV) and sound amplitude (DeltaA) was examined. The amplitude of normal lung sounds was reduced by application of PEEP >or=10 cm H(2)O (P<0.05). The increase in PEEP from 0 to 20 cm H(2)O reduced the acoustic energy of lung sounds recorded at ZEEP by 0.3 dB (PEEP 5), 2 dB (PEEP 10), 5 dB (PEEP 15) and 7 dB (PEEP 20), which corresponds to 1%, 6%, 14% and 21% in acoustic attenuation, respectively. The variations in DeltaA correlated with changes in lung volume (P<0.05) and with changes in compliance of the respiratory system (P<0.05), but were not correlated with changes of the resistance of respiratory system. The frequency analysis showed a downward shifting of the spectra at frequencies between 150 and 600 Hz for PEEP levels >or=10 cm H(2)O and frequencies between 75 and 600 Hz for PEEP levels >or=15 cm H(2)O. The application of increasing levels of PEEP reduced the amplitude and changed the spectral characteristics of normal lung sounds.

Acoustics↗
PubMed2006

The central circulation in congestive heart failure non-invasively evaluated with dynamic positron emission tomography.

BACKGROUND: Positron emission tomography (PET) with [15O]-H2O-PET (WAT-PET) or [11C]-acetate (AC-PET) quantifies myocardial perfusion and oxidative metabolism, but routine clinical use is hampered by the need for additional investigations to assess cardiac performance. OBJECTIVE: To apply classical tracer kinetics to dynamic PET could provide important haemodynamic parameters. METHODS: First-pass PET data were used with indicator dilution techniques to measure stroke volume index (SVI). Early pulmonary retention of [11C]-acetate was converted to standard uptake values (SUV) (Lung(AC-SUV)). Regional lung water (rLW) content was computed from the WAT-PET scan at equilibrium. PET was compared with radionuclide angiography and echocardiography in patients with ischaemic cardiomyopathy with New York Heart Association class II (n = 10) or III (n = 18) congestive heart failure. Elderly male volunteers without heart disease (n = 11) underwent AC-PET as controls. RESULTS: SVI with both tracers correlated in patients (r = 0.91, P<0.001, estimated standard error = 4 ml m(-2)) and with left ventricular ejection fraction (both tracers r>0.6, P<0.001). SVI was significantly different between all groups (ANOVA: P<0.001). Lung(AC-SUV) correlated with rLW (r = 0.78, P<0.001) and both were elevated in severe heart failure (P<0.05 for both). Elevated Lung(AC-SUV) was associated with a restrictive left ventricular (LV) filling pattern by Doppler echocardiography. CONCLUSION: Dynamic PET with first-pass analysis and tracers of myocardial perfusion enables quantification of the haemodynamic consequences of LV systolic and diastolic dysfunctions in ischaemic cardiomyopathy and could be useful in the evaluation of the central circulation in heart failure.

Acetates↗
PubMed2006

Change in expiratory flow detects partial endotracheal tube obstruction in pressure-controlled ventilation.

Only extreme degrees of endotracheal tube (ETT) narrowing can be detected with monitoring of tidal volume (V(T)) during pressure-controlled ventilation (PCV). To assess the degree of ETT obstruction in PCV and to compare it to V(T) monitoring, we produced 3 levels of partial ETT obstruction in 11 healthy anesthetized piglets using ETTs of 4 different inner diameters (IDs 9.0, 8.0, 7.0, and 6.0 mm). An expiratory flow over volume ((e)-V) curve was plotted and the time constant (tau(e)) at 15% of expiration time (T(e)) was calculated. We also calculated the fractional volume expired during the first 15% of T(e) (V(ex fract,15)) and compared those variables to full expiratory V(T) for each of the 3 obstructions. V(T) monitoring failed to detect ETT narrowing. By contrast, V(ex fract,15) decreased and tau(e) increased significantly with increasing ETT narrowing (for IDs 9.0, 8.0, 7.0, and 6.0, mean V(ex fract,15) was 195, 180, 146, and 134 mL respectively and mean tau(e) was 380, 491, 635, 794 ms for IDs 9.0, 8.0, 7.0, and 6.0 respectively). We conclude that when the elastic recoil that drives (e) is appropriately considered, analysis of (e) and V(ex fract,15) detects partial ETT obstruction during PCV.

Airway Obstruction↗
PubMed2005

Spontaneous breathing with airway pressure release ventilation favors ventilation in dependent lung regions and counters cyclic alveolar collapse in oleic-acid-induced lung injury: a randomized controlled computed tomography trial.

INTRODUCTION: Experimental and clinical studies have shown a reduction in intrapulmonary shunt with spontaneous breathing during airway pressure release ventilation (APRV) in acute lung injury. This reduction was related to reduced atelectasis and increased aeration. We hypothesized that spontaneous breathing will result in better ventilation and aeration of dependent lung areas and in less cyclic collapse during the tidal breath. METHODS: In this randomized controlled experimental trial, 22 pigs with oleic-acid-induced lung injury were randomly assigned to receive APRV with or without spontaneous breathing at comparable airway pressures. Four hours after randomization, dynamic computed tomography scans of the lung were obtained in an apical slice and in a juxtadiaphragmatic transverse slice. Analyses of regional attenuation were performed separately in nondependent and dependent halves of the lungs on end-expiratory scans and end-inspiratory scans. Tidal changes were assessed as differences between inspiration and expiration of the mechanical breaths. RESULTS: Whereas no differences were observed in the apical slices, spontaneous breathing resulted in improved tidal ventilation of dependent lung regions (P < 0.05) and less cyclic collapse (P < 0.05) in the juxtadiaphragmatic slices. In addition, with spontaneous breathing, the end-expiratory aeration increased and nonaerated tissue decreased in dependent lung regions close to the diaphragm (P < 0.05 for the interaction ventilator mode and lung region). CONCLUSION: Spontaneous breathing during APRV redistributes ventilation and aeration to dependent, usually well-perfused, lung regions close to the diaphragm, and may thereby contribute to improved arterial oxygenation. Spontaneous breathing also counters cyclic collapse, which is a risk factor for ventilation-associated lung injury.

Animals↗
PubMed2005

The effects of anesthesia and muscle paralysis on the respiratory system.

BACKGROUND: Oxygenation is impaired in almost all subjects during anesthesia, and hypoxemia for shorter or longer periods is a common finding. Moreover, postoperative lung complications occur in 3-10% after elective abdominal surgery and more in emergency operations. DISCUSSION: Rapid collapse of alveoli on induction of anesthesia and more widespread closure of airways seem to explain the oxygenation impairment and may also contribute to postoperative pulmonary infection. Causative mechanisms to atelectasis and airway closure seem to be loss of respiratory muscle tone and gas resorption. CONCLUSION: Avoiding high inspired oxygen fractions during both induction and maintenance of anesthesia prevents or reduces atelectasis, while intermittent "vital capacity" maneuvers recruit atelectatic lung regions.

Anesthesia↗
PubMed2005

Effects of hyperosmolarity and airway epithelial ion transport inhibitors on sodium nitroprusside-induced relaxation of guinea pig trachea.

Increased airway surface osmolarity has been shown to abolish the airway relaxant effects of inhaled nitric oxide. We have investigated the effects of increased airway surface osmolarity on airway relaxation induced by nitric oxide. The physiological responses, obtained by a guinea pig tracheal perfusion method, were compared to the ion content of the tracheal tissues, and the effects of amiloride or furosemide were studied. Hyperosmolarity decreased the ability of sodium nitroprusside (SNP) to relax carbachol-constricted trachea. Light microscopy showed shrinkage of the epithelial cells and X-ray microanalysis showed increased epithelial ion content under conditions of intraluminal hyperosmolarity, suggesting dehydration of the epithelium. Amiloride treatment reduced the increase in epithelial ion content but had no effect on shrinkage or SNP-induced relaxation. Furosemide had no effect on the altered ion content, shrinkage, or on SNP-induced relaxation. In conclusion, neither amiloride nor furosemide can counteract the shrinkage of the airway wall induced by increased osmolarity in the lumen of guinea pig trachea in vitro, nor can they affect the reduction in relaxing response to the NO-donor SNP.

Amiloride↗
PubMed2005

Suctioning through a double-lumen endotracheal tube helps to prevent alveolar collapse and to preserve ventilation.

OBJECTIVE: Endotracheal suctioning can cause alveolar collapse and impede ventilation. One reason is the gas flow through a single-lumen endotracheal tube (ETT) provoking a gradient between airway opening and tracheal (P(tr)) pressures. Separately extending the patient tubing limbs of a suitable ventilator into the trachea via a double-lumen ETT should maintain P(tr). Can this technique reduce the side effects? DESIGN AND SETTING: Bench and animal studies in a university hospital laboratory. INTERVENTIONS: A lung model was ventilated via single and double-lumen ETTs. Closed-system suctioning was applied with catheters introduced into the single-lumen ETT or the expiratory lumen of the double-lumen ETT via swivel adapter. Seven anesthetized pigs (lungs lavaged) underwent three runs of ventilation and suctioning through (a, b) an 8.0-mm ID single-lumen ETT, (c) a double-lumen ETT (41Ch outer diameter, OD). In (a) the single-lumen ETT was disconnected for suctioning, in (b) and (c) ventilator mode was set to continuous positive airway pressure mode, and the ETTs remained connected. MEASUREMENTS AND RESULTS: Bench: Suction through single-lumen ETTs impaired ventilation and led to strongly negative P(tr) (common: -10 to -20 mbar); the double-lumen ETT technique maintained ventilation and pressures. ANIMALS: Lung gas content (computed tomography, n=4) and arterial oxygen partial pressure, initially 1462+/-65 ml/532+/-76 mmHg, were significantly reduced by suctioning through single-lumen ETT: to 302+/-79 ml/62+/-6 mmHg with disconnection and to 851+/-211 ml/158+/-107 mmHg with closed suction. With double-lumen ETT they remained at 1377+/-95 ml/521+/-56 mmHg. CONCLUSIONS: The double-lumen ETT technique minimizes side effects of suctioning by maintaining P(tr).

Animals↗
PubMed2005

The lung during and after thoracic anaesthesia.

PURPOSE OF REVIEW: Increased awareness of widespread atelectasis and deoxygenation after cardiac surgery, and in the ventilated lung during one-lung anaesthesia, has prompted many studies on recruitment of collapsed tissue and other methods to treat hypoxia in the perioperative period. It is therefore time to summarize what benefits might come from such manoeuvres. RECENT FINDINGS: Major findings are that recruitment by different, often vigorous inflation of the lungs improves oxygenation and that this can also be seen when a recruitment manoeuvre is done of the ventilated lung in one-lung anaesthesia. The inspired oxygen fraction seems to be an important determinant of how long the recruitment persists. SUMMARY: Recruitment manoeuvres are highly efficient in improving oxygenation but often for a limited period. So they have to be repeated. To what extent they may affect hospital stay and other variables of outcome, remains to be shown.

Journal Article↗
PubMed2005

Spontaneous breathing affects the spatial ventilation and perfusion distribution during mechanical ventilatory support.

OBJECTIVE: In acute respiratory failure, gas exchange improves with spontaneous breathing during airway pressure release ventilation (APRV). The mechanisms for this improvement are not fully clear. We have shown that APRV with spontaneous breathing reopens nonaerated lung tissue in dorsal juxtadiaphragmatic regions. We hypothesized that spontaneous breathing during APRV may redistribute ventilation and perfusion toward these reopened regions. DESIGN: Prospective, randomized, controlled study. SETTING: Animal research laboratory SUBJECTS: Twenty controlled mechanically ventilated pigs. INTERVENTIONS: Lung injury was induced by injection of oleic acid into the central circulation; thereafter, pigs were randomized to APRV with or without spontaneous breathing. To induce spontaneous breathing during APRV with spontaneous breathing, the mechanical respiratory rate was decreased by 50% in this group. MEASUREMENTS AND MAIN RESULTS: We measured respiratory mechanics, hemodynamics, gas exchange including the multiple inert gas elimination technique, and the spatial ventilation and perfusion distribution using single photon emission tomography. At similar minute ventilation and airway pressures, shunt remained stable during APRV with spontaneous breathing, whereas it increased during APRV without spontaneous breathing during the 2-hr study period (p = .006). Single photon emission tomography showed more ventilation (p < .001) and pulmonary blood (p < .025) flow in dorsal, juxtadiaphragmatic lung regions when spontaneous breathing was present. CONCLUSIONS: The beneficial effects of spontaneous breathing on intrapulmonary shunt and oxygenation are explained both by increased ventilation of aerated dependent lung tissue and by opening up nonaerated tissue so that ventilation is distributed to a larger share of the lung. Redistribution of perfusion is possibly secondary to the altered ventilation. The overall effect is a more efficient use of available lung tissue for gas exchange.

Animals↗
PubMed2005

Effects of acepromazine on pulmonary gas exchange and circulation during sedation and dissociative anaesthesia in horses.

OBJECTIVE: To study pulmonary gas exchange and cardiovascular responses to sedation achieved with romifidine and butorphanol (RB) alone, or combined with acepromazine, and during subsequent tiletamine-zolazepam anaesthesia in horses. ANIMALS: Six (four males and two females) healthy Standardbred trotters aged 3-12 years; mass 423-520 kg. STUDY DESIGN: Randomized, cross-over, experimental study. MATERIALS AND METHODS: Horses were anaesthetized on two occasions (with a minimum interval of 1 week) with intravenous (IV) tiletamine-zolazepam (Z; 1.4 mg kg(-1)) after pre-anaesthetic medication with IV romifidine (R; 0.1 mg kg(-1)) and butorphanol (B; 25 microg kg(-1) IV). At the first trial, horses were randomly allocated to receive (protocol ARBZ) or not to receive (protocol RBZ) acepromazine (A; 35 microg kg(-1)) intramuscularly (IM) 35 minutes before induction of anaesthesia. Each horse was placed in left lateral recumbency and, after tracheal intubation, allowed to breathe room air spontaneously. Respiratory and haemodynamic variables and ventilation-perfusion (; multiple inert gas elimination technique) ratios were determined in the conscious horse, after sedation and during anaesthesia. One- and two-way repeated-measures anova were used to identify within- and between-technique differences, respectively. RESULTS: During sedation with RB, arterial oxygen tension (PaO(2)) decreased compared to baseline and increased mismatch was evident; there was no O(2) diffusion limitation or increase in intrapulmonary shunt fraction identified. With ARB, PaO(2) and remained unaffected. During anaesthesia, intrapulmonary shunt occurred to the same extent in both protocols, and mismatching increased. This was less in the ARBZ group. Arterial O(2) tension decreased in both protocols, but was lower at 25 and 35 minutes of anaesthesia in RBZ than in ARBZ. During sedation, heart rate (HR) and cardiac output (Qt) were lower while arterial-mixed venous oxygen content differences and haemoglobin concentrations were higher in RBZ compared with ARBZ. Total systemic vascular resistance, mean systemic, and mean pulmonary arterial pressures were higher during anaesthesia with RBZ compared to ARBZ. CONCLUSIONS AND CLINICAL RELEVANCE: Acepromazine added to RB generally improved haemodynamic variables and arterial oxygenation during sedation and anaesthesia. Arterial oxygenation was impaired as a result of increased shunt and mismatch during anaesthesia, although acepromazine treatment reduced disturbances and falls in PaO(2) to some extent. Haemodynamic variables were closer to baseline during sedation and anaesthesia when horses received acepromazine. Acepromazine may confer advantages in healthy normovolaemic horses.

Acepromazine↗