Anesth Analg 2003;96:1035-1041
© 2003 International Anesthesia Research Society
ANESTHETIC PHARMACOLOGY
The Effects of Propofol and Etomidate on Airway Contractility in Chronically Hypoxic Rats
Nazinigouba Ouédraogo, MD*,
,
Roger Marthan, MD PhD*, and
and Etienne Roux, DMV PhD*
*Laboratoire de Physiologie Cellulaire Respiratoire, INSERM EMI9937, Université Victor Segalen, Bordeaux, France; and
UFR/SDS Université de Ouagadougou, Burkina Faso, Africa
Address correspondence and reprint requests to Etienne Roux, Laboratoire de Physiologie cellulaire respiratoire, EMI 9937, Université Victor Segalen Bordeaux 2, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France. Address e-mail to etienne.roux{at}u-bordeaux2.fr
 |
Abstract
|
|---|
We investigated the effect of two IV anesthetics, propofol and etomidate, on airway responsiveness in a rat model of chronic hypoxia (CH) in comparison with normoxic rats. CH rats were obtained using a hypobaric chamber (14 days at a barometric pressure of 380 mm Hg). The ability of both anesthetics to relax and prevent agonist-induced contraction was assessed in isolated tracheal rings precontracted with the muscarinic agonist carbachol (CCh) and the depolarizing agent KCl. Cumulative concentrations of both compounds relaxed tracheal rings precontracted with CCh or KCl with a similar amplitude in CH and normoxic rats. In tracheal rings precontracted with CCh, the negative logarithm of anesthetics that reduced the maximal contraction by 30%, i.e., -log half-maximal inhibitory concentration, for propofol and etomidate were 4.10 ± 0.09 and 4.12 ± 0.15 in normoxic rats and 4.20 ± 0.22 and 3.61 ± 0.19 in CH rats, respectively. At a fixed concentration, propofol (3 x 10-4 M) or etomidate (10-4 M) also inhibited CH tracheal rings contraction in response to cumulative concentrations of CCh and KCl. However, in contrast with the equivalent relaxant effect of both anesthetics, etomidate was two-fold less effective than propofol for inhibiting the subsequent contraction to CCh and KCl. These results indicate that propofol and etomidate retain their relaxant properties in CH rat airways by acting on the pharmaco- and electromechanical coupling.
IMPLICATIONS: Anesthesia may cause airway constriction or bronchospasm in patients with normal or pathological airways. This study investigated the ability of propofol and etomidate to both reverse precontraction and inhibit contraction of tracheal rings isolated from chronically hypoxic rats.
|
Introduction
|
|---|
The induction of anesthesia and intubation of the trachea may cause airway constriction, and perioperative bronchospasm may occur in patients with normal or pathological airways (1). The effect of IV anesthetics on airway responsiveness is thus important to consider, in particular their ability to reverse bronchoconstriction. Various studies have been performed to assess the effects of compounds such as ketamine, propofol, and, to a lesser degree, etomidate on airway smooth muscle and bronchoconstriction (2–5) . These studies have shown that these anesthetics reduce airway reactivity by an indirect action on airway neural control or by a direct action on the airway smooth muscle cell. In particular, propofol and etomidate have been shown to decrease both pharmaco- and electromechanical coupling (6). Acting on pharmacomechanical coupling, they reduce the Ca2+ response to muscarinic agonists, likely by inhibition of InsP3 production (7). They also act on the electromechanical coupling because they inhibit calcium influx after cell depolarization (6). In this connection, various authors have demonstrated that propofol inhibits L-type voltage-dependent Ca2+ channels (8).
Most of these experimental studies have been performed on normal airways. However, in several pathological conditions, stimulation-contraction coupling and hence airways reactivity may be altered. In a rat model, we have shown that chronic hypoxia (CH), a condition often associated with chronic obstructive pulmonary disease, increased airway sensitivity and decreased the maximal response to muscarinic stimulation without significant changes in airway histology. Hypersensitivity, but not maximal contraction decrease, correlated with changes in the characteristics of the calcium response, i.e., the amplitude of the Ca2+ peak and the frequency of Ca2+ oscillations (9,10) . The effect of anesthetics may then differ in normoxic versus hypoxic airways. Few studies have been performed on the effect of anesthetics under hypoxic conditions. In vitro experiments on pig tracheal rings have shown that volatile anesthetics inhibit carbachol (CCh)-induced contraction (11) under acute hypoxia, but no experimental studies have been performed to assess the effect of IV anesthetics in chronically hypoxic airways.
The aim of the present study was thus to assess the effect of propofol and etomidate on airway responsiveness of chronically hypoxic rats. Because the mechanisms implicated in the development of force may differ from those involved during sustained contraction in smooth muscle (12,13) , we investigated the ability of these compounds to both reverse airway precontraction and inhibit airway contraction.
|
Materials and Methods
|
|---|
The rats used in this study were treated and killed in accordance with national guidelines, and the protocol was approved by a local committee for animal care. Male Wistar rats, 8–10 wk old, were exposed to a simulated altitude of 5500 m (barometric pressure 380 mm Hg) in a well-ventilated, temperature-controlled hypobaric chamber for 14 days, as previously described (9). Such a protocol generates CH, which in turn provokes pulmonary artery hypertension and right ventricular hypertrophy evidenced by an increase in the ratio of right ventricle to left ventricle + septum weight (9,10) . Normoxic rats were kept under similar conditions but not in the hypobaric chamber. For each experiment, a rat was killed by cervical dislocation. The heart and lungs were removed en-bloc, and the trachea was rapidly dissected out. For isometric contraction experiments, each trachea was cut into six rings of similar diameter, i.e., approximately 4 mm, and approximately 3 mm in length. To avoid possible biases because of variations in ring size, contraction was normalized to a reference functional response (see below).
Isometric tension was measured in intact tracheal rings that were mounted between 2 stainless steel clips in vertical 20-mL organ baths of a computerized isolated organ bath system (IOX, EMKA Technologies, Paris, France), as previously described (6,9) . Baths were filled with Krebs-Henseleit (KH) solution (composition given below) maintained at 37°C and bubbled with a 95% O2:5% CO2 gas mixture. The upper stainless clip was connected to an isometric force transducer (EMKA Technologies). Tissues were set at optimal length by equilibration against a passive load of 1.5 g, as previously determined for these types of preparation (10).
The relaxant effect of cumulative concentrations of etomidate and propofol on precontraction to CCh and KCl was assessed as follows. At the beginning of each experiment, before exposure to anesthetics, a contraction was elicited by the muscarinic agonist CCh (10-3 M) or KCl (80 mM). According to the Nernst equation, this concentration of KCl depolarizes the membrane potential close to -10 mV, which opens the voltage-operated Ca2+ channels and thus activates the electromechanical coupling. When the maximal contraction was obtained, propofol or etomidate was added to the tracheal rings in cumulative half-log increments from 10-6 to 10-3 M. In each trachea, duplicate rings were studied for each anesthetic, and two rings were used as time control to assess for the temporal changes in the tension elicited by CCh or KCl. The ring tension was measured when the response stabilized, i.e., after an equilibration time of approximately 15 min and expressed as a percentage of the maximal initial contraction of that ring.
The effect of fixed concentrations of etomidate and propofol on the subsequent cumulative concentration-response curve (CCRC) to CCh (10-8 to 10-4 M) and KCl (2 x 10-3 to 10-1 M) was assessed as follows. At the beginning of each experiment, supramaximal stimulation with acetylcholine (ACh) (10-3 M final concentration in the bath) was administered to each of the rings to elicit a reference response that was used to normalize the subsequent contractile responses. After washing the rings with fresh KH solution to eliminate the ACh response, propofol (3 x 10-4 M) and etomidate (10-4 M) were added 20 min before the beginning of the CCRC. These fixed concentrations of anesthetics have been chosen according to our previous studies in normoxic rat tracheae and human isolated bronchi (6).
ACh and carbamylcholine chloride were purchased from Sigma (Saint Quentin Fallavier, France). Propofol (Diprivan®, Zenecca laboratories, Cergy, France) and etomidate (Hypnomidate®, Janssen laboratories, Boulogne Billancourt, France) were obtained from their clinically used presentations. We verified that the vehicle of each of the drugs had no effect per se on contractile responses. In particular, the solvent for propofol (Ivelip® 10%, Clintec nutrition clinique, Amiely, France) was without effect up to the maximal concentration used in the present experiments (i.e., 1.5%). Composition of KH solution was (in mM): NaCl 118.4, KCl 4.7, CaCl2 2.5, MgSO4 1.2, KH2PO4 1.2, NaHCO3 25.0, and D-glucose 11.1, with a pH value of 7.4. For KCl-induced contraction, KCl was substituted for NaCl for the desired concentrations to keep the osmotic pressure constant.
In relaxation experiments, to take into account the time-dependent change in contraction in control conditions, the relaxation induced by each concentration of anesthetic was expressed as a percentage of the contractile response of the paired temporal control. The resulting concentration-dependent relaxation curves were fitted by a nonlinear Boltzmann equation to determine the concentrations of anesthetics that reduced the maximal contraction by 50% (IC50) and by 30% (IC30), reported as a negative logarithm (pIC50 and pIC30, respectively), according to Lovren and Triggle (14). Rmax refers to the maximal relaxation obtained at the maximal anesthetic concentration (10-3 M), where 100% denotes a complete reversal of initial contraction.
In contraction experiments, the variables derived from each CCRC were the maximal contractile force (Fmax) and the potency of the contractile agonist characterized as the 50% effective concentration (EC50), which were calculated by fitting curves using a nonlinear regression equation writing:
|
where F is the force, Fmax the maximal force, C the concentration, EC50 the concentration producing half-maximal force (pEC50 = -logEC50), and n the Hill coefficient. Change in airway reactivity induced by anesthetics was defined as 
Fmax, the difference between Fmax in exposed and unexposed tissues expressed as the percentage of Fmax in the control rings. In relaxation as well as in contraction experiments, overall cumulative concentration-response curves and the derived variables were compared using analysis of variance for repeated measures followed, when needed, by Student’s t-test with Bonferroni correction as post hoc tests using the SPSS® statistical software (SPSS Inc, Chicago, IL). Experiments were performed on duplicate rings, and each experimental condition was repeated on six different rat tracheae. Data are given as mean ± SEM. Differences were considered significant when P < 0.05.
|
Results
|
|---|
Figure 1A shows the CCRC along with the paired temporal control. Etomidate fully relaxed CCh-induced contraction in tissues from both normoxic and CH rats, whereas propofol was less effective in both conditions. However, overall comparison of the curves indicated that the difference in the efficacy of etomidate and propofol was significant in CH tissues only. Values of Rmax, pIC50, and pIC30 are given in Table 1. Because in clinical practice etomidate and propofol are not used at similar concentrations, we also compared the relaxant effect of etomidate at 10-4 M and propofol 3 x 10-4 M, i.e., the fixed concentrations used in contraction experiments and previously determined in normoxic rat tracheae and human bronchi (6). At these concentrations, both etomidate and propofol significantly relaxed normoxic and CH tracheae, but there was no statistical difference in the effect of propofol versus etomidate or on normoxic versus CH tissues for any compound. Amplitudes of relaxation are given in Figure 4, A and B, left panels.
View larger version (14K):
[in this window]
[in a new window]
|
Figure 1. Relaxant effect of cumulative concentrations of etomidate and propofol in normoxic and chronically hypoxic (CH) rat tracheal rings precontracted with carbachol (CCh; 10-3 M). Abscissa = log concentration of anesthetics (M); Ordinate = isometric contraction (percentage of the initial contraction to 10-3 M of CCh); Open circles = unexposed temporal control; Full squares = rings exposed to etomidate; Full down triangles = rings exposed to propofol. (A) Normoxic tissues. (B) CH tissues. Each symbol is the mean value from six specimens. Vertical bars are SEM. *P < 0.05 versus control.  P < 0.05 etomidate versus propofol.
|
|
View this table:
[in this window]
[in a new window]
|
Table 1. The Relaxant Effect of Etomidate and Propofol on Rat Isolated Tracheal Rings Precontracted with 10-3 M of Carbachol
|
|
View larger version (27K):
[in this window]
[in a new window]
|
Figure 4. Effect of 10-4 M of etomidate and 3 x 10-4 M of propofol on agonist-induced airway contraction. (A) Relaxant effect of etomidate and propofol on normoxic tracheal rings precontracted with 10-3 M of carbachol (CCh) (closed columns) and 80 mM of KCl (open columns). (B) Relaxant effect of etomidate and propofol on chronically hypoxic (CH) tracheal rings precontracted with 10-3 M of CCh (closed columns) and 80 mM of KCl (open columns). (C) Effect of etomidate and propofol on the maximal response to cumulative concentrations of CCh (crosshatched columns) and KCl (hatched columns) in CH tracheal rings. Data are the mean values from six specimens. Vertical bars are SEM. P < 0.05 etomidate versus propofol.
|
|
In control rings, there was a slight time-dependent decrease in the contraction. Both compounds fully relaxed KCl-induced contraction. At equivalent concentrations, the effect of etomidate and propofol was identical and was similar in normoxic and in CH rings (Fig. 2). Values of Rmax, pIC50, and pIC30 are given in Table 2. The amplitude of relaxation induced by 10-4 M of etomidate and 3 x 10-4 M of propofol was larger than that obtained in rings precontracted with CCh. At these concentrations, there was no statistical difference in the effect of propofol versus etomidate or on normoxic versus CH tissues for any compound. Results are illustrated in Figure 4, A and B, right panels.
View larger version (14K):
[in this window]
[in a new window]
|
Figure 2. Relaxant effect of cumulative concentrations of etomidate and propofol in normoxic and chronically hypoxic (CH) rat tracheal rings precontracted with KCl (80 mM). Abscissa = log concentration of anesthetics (M); Ordinate = isometric contraction (percentage of the initial contraction to 80 mM KCl); Open circles = unexposed temporal control; Full squares = rings exposed to etomidate; Full down triangles = rings exposed to propofol. (A) Normoxic tissues. (B) CH tissues. Each symbol is the mean value from six specimens. Vertical bars are SEM. *P < 0.05 versus control.
|
|
View this table:
[in this window]
[in a new window]
|
Table 2. The Relaxant Effect of Etomidate and Propofol on Rat Isolated Tracheal Rings Precontracted with 80 mM of KCl.
|
|
In these series of experiments, we assessed the effect of a fixed concentration of propofol (3 x 10-4 M) and etomidate (10-4 M). Because the effect of both compounds had already been assessed in normoxic tissues using a similar protocol, the present experiments were restricted to CH airways.
In the absence of anesthetics, the maximal response was 126.1% ± 10.2% of the ACh reference response, and pEC50 was 6.47 ± 0.4. Overall comparison of the CCRC showed that both propofol (3 x 10-4 M) and etomidate (10-4 M) significantly inhibited muscarinic contraction (Fig. 3A). However, in contrast with the results obtained regarding the relaxant properties at these concentrations, propofol was more potent than etomidate to inhibit contraction, as shown in Figure 3A. The Fmax was significantly reduced in the presence of propofol (67.9% ± 9.9% of the ACh reference response; P < 0.05) and of etomidate, although to a lesser degree (101.9% ± 4.0% of the ACh reference response; P < 0.05). The comparison in the decrease of the maximal response is illustrated in Figure 4C, left panel. Both propofol and etomidate significantly shifted the CCRC to the right, the pEC50 being 5.69 ± 0.13 (P < 0.05) and 6.15 ± 0.12 (P < 0.05), respectively.
View larger version (15K):
[in this window]
[in a new window]
|
Figure 3. Effect of etomidate and propofol on cumulative concentration response curve (CCRC) to contractile drugs in chronically hypoxic (CH) rat trachea rings. Abscissa = cumulative concentrations of contractile drug (logM); Ordinate = mean contractile response, expressed as percentage of acetylcholine (ACh) reference response in the absence of anesthetics (open circles) and in the presence of 10-4 M of etomidate (full squares) and 3 x 10-4 M of propofol (full down triangles). (A) CCRC to carbachol (CCh). (B) CCRC to KCl. Each symbol is the mean value from six specimens. Vertical bars are SEM. *P < 0.05 versus control; P < 0.05 etomidate versus propofol.
|
|
Effect on CCRC to KCl
In control tissues, maximal contraction to 80 mM of KCl was 86.3% ± 5.6% of the ACh reference response. As shown in Figure 3B and 4C, both anesthetics inhibited the KCl-induced contraction. Etomidate reduced the maximal contractile response to 46.3% ± 5.2% of the ACh reference response (P < 0.05), and propofol nearly completely abolished it (10.6% ± 7.0%; P < 0.05).
|
Discussion
|
|---|
The results of the present study indicate that the IV anesthetics etomidate and propofol relax precontracted airways. The efficacy of etomidate and propofol to reverse contraction is rather similar and is of equivalent amplitude in tissues from normoxic versus CH rats. Exposure to etomidate and propofol also reduces the subsequent contraction to cumulative concentrations of both the muscarinic agonist CCh and the depolarizing agent KCl in airways from CH rats. However, etomidate was less effective than propofol in inhibiting contraction in contrast with its relaxant properties. Propofol and etomidate thus retain their relaxing properties in airways from CH rats.
Both etomidate and propofol relaxed airways precontracted by the muscarinic drug CCh. These results are in accordance with those obtained in dog airways (5), where 10-4 M of propofol induced relaxation in isolated tracheal rings precontracted with ACh, without any effect at 10-5 M. It should be noticed that, in our experiments, a relaxation was observed for smaller propofol concentrations. Propofol concentrations that induced 30% relaxation in normoxic and CH tissues were approximately 6 to 8 x 10-5 M, a value in the range of plasma concentrations calculated in in vivo experiments in dogs (15) and sheep (16), as well as in clinical studies on ventilated patients (17). For identical concentrations, etomidate seemed to have a greater effect than that of propofol, in particular in tissues from CH animals. However, because clinically used doses of etomidate are usually smaller than those of propofol (18–20) , clinically relevant comparison, i.e., a comparison taking into account a half-log difference between etomidate and propofol concentrations, suggests that the effect of both compounds is similar.
As previously observed in airways from normoxic rats (4,6) , etomidate and propofol administered at a fixed concentration inhibited the subsequent contraction of isolated rings from CH rats. The amplitude of the effect of propofol observed in rings from CH rats was similar to that previously observed in normoxic-isolated tracheae (6). In contrast, etomidate seems to have a smaller effect on tissues from CH rats, especially on the CCh-induced contraction. In our previous experiments, the decrease in maximal contraction induced by 10-4 M of etomidate was approximately 25%, whereas it was <15% in the present study on CH rats.
Muscarinic stimulation induces contraction mainly via InsP3 production and Ca2+ release from the sarcoplasmic reticulum, the so-called pharmacomechanical coupling (21). Both propofol and etomidate have been shown to act on this coupling. Propofol and etomidate inhibited Ca2+ release from the sarcoplasmic reticulum in airway myocytes (6,7) , an effect that was likely caused by the inhibition of inositol-phosphate production (7). This effect on calcium signaling in airway myocytes may account for the relaxant as well as the anticontractant effects of these anesthetics in both normoxic and CH airways. To further investigate the mechanisms of action of etomidate and propofol, we assessed their effect on airways stimulated by the depolarizing agent KCl. The fact that both anesthetics abolished the KCl-induced contraction indicates that they also act on the electromechanical coupling. Such an effect has been demonstrated in normoxic cells (6–8) and seems to be also operative in tissues from CH rats.
Because, in smooth muscle, the mechanisms implicated in the development of force may differ from those that are involved during sustained contraction (12,13) , we have compared the ability of both compounds to induce relaxation and to inhibit airway contraction at identical concentrations, i.e., 10-4 M of etomidate and 3 x 10-4 M of propofol. The present results obtained from CH rats indicate that the ability of propofol at inhibiting and at reversing contraction was similar. By contrast, whereas the ability of etomidate at reversing contraction was similar to that of propofol, it was two-fold less efficient at inhibiting a subsequent contraction. Such a difference was observed for contractions induced by muscarinic stimulation as well as by the depolarizing agent KCl. In tonic smooth muscles, such as in airways, the sustained contraction is associated with an increase in the sensitivity of the contractile apparatus to calcium (12). A possible explanation for the differential effect of etomidate on contraction inhibition and reversion may be that etomidate increases myofilament Ca2+ sensitivity. Such an effect has been demonstrated for volatile anesthetics (22) but does not seem to be involved in the mechanisms of action of propofol on airway smooth muscle (23). This hypothesis about the effect of etomidate requires further examination.
In our experimental design, trachea was used as a model of airway smooth muscle, assuming that the mechanisms involved in airway contraction and relaxation are basically similar in proximal and distal airways. This tracheal model has been widely used to investigate the effect of volatile and IV anesthetics on airway reactivity both in normoxia (2,4,7,8,22,23) and acute hypoxia (11). However, trachea is not the anatomic site of bronchospasm, which corresponds to distal intrapulmonary bronchi. Though the main mechanisms involved in airway reactivity are thought to be similar in trachea and bronchi, there are differences in the sensitivity to anesthetics along the respiratory track. In dog airways, the relaxant effects of ketamine, midazolam, and propofol are more pronounced in distal versus proximal airway smooth muscle (5). Similarly, in porcine airways, the inhibitory effects of the volatile anesthetics isoflurane and sevoflurane on tension, intracellular calcium, and Ca2+ currents were greater in bronchial versus tracheal smooth muscle (24). The effect of propofol and etomidate evidenced in this study on tracheal rings may then vary in amplitude along the site in the airways.
The fact that the relaxant effect of etomidate and propofol is observed for concentrations that are in the range of clinically used doses, as discussed above, may be of clinical interest. The IC30 of propofol, for example, was one log less than the calculated bronchial artery plasma concentration in sheep anesthetized with clinically relevant propofol doses (16). However, one should be cautious in extrapolating ex vivo data to in vivo conditions, in particular because of the high protein binding of these compounds that decreases their free concentrations and hence their biological effect (25).
In conclusion, our study has demonstrated that propofol and etomidate inhibit and reverse contraction in airways from CH rats, acting both on the pharmaco- and electromechanical coupling. The ability of both compounds at reversing contraction is similar, whereas propofol is more effective than etomidate for inhibiting contraction. The effect of propofol is similar in tissues from normoxic and CH rats. In contrast, etomidate is less efficient in inhibiting contraction in CH rats. The clinical relevance of these observations requires further investigations.
|
Acknowledgments
|
|---|
Supported, in part, by Institut National de la Santé et de la Recherche Médicale (INSERM) and Agence pour le Développement et la Maîtrise de l’Énergie (ADEME).
The authors are grateful to Mrs Hugette Crevel and Mr Pierre Téchoueyres for technical assistance.
|
References
|
|---|
- Hirshman CA, Bergman NA. Factors influencing intrapulmonary airway calibre during anaesthesia. Br J Anaesth 1990; 65: 30–42.[Free Full Text]
- Pedersen CM, Thirstrup S, Nielsen-Kudsk JE. Smooth muscle relaxant effects of propofol and ketamine in isolated guinea-pig trachea. Eur J Pharmacol 1993; 238: 75–80.[ISI][Medline]
- Wilson LE, Hatch DJ, Rehder K. Mechanisms of the relaxant action of ketamine on isolated porcine trachealis muscle. Br J Anaesth 1993; 71: 544–50.[Abstract/Free Full Text]
- Hashiba E, Sato T, Hirota K, et al. The relaxant effect of propofol on guinea pig tracheal muscle is independent of airway epithelial function and beta-adrenoceptor activity. Anesth Analg 1999; 89: 191–6.[Abstract/Free Full Text]
- Cheng EY, Mazzeo AJ, Bosnjak ZJ, et al. Direct relaxant effects of intravenous anesthetics on airway smooth muscle. Anesth Analg 1996; 83: 162–8.[Abstract]
- Ouedraogo N, Roux E, Forestier F, et al. Effects of intravenous anesthetics on normal and passively sensitized human isolated airway smooth muscle. Anesthesiology 1998; 88: 317–26.[ISI][Medline]
- Lin CC, Shyr MH, Tan PP, et al. Mechanisms underlying the inhibitory effect of propofol on the contraction of canine airway smooth muscle. Anesthesiology 1999; 91: 750–9.[ISI][Medline]
- Yamakage M, Hirshman CA, Croxton TL. Inhibitory effects of thiopental, ketamine, and propofol on voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells. Anesthesiology 1995; 83: 1274–82.[ISI][Medline]
- Belouchi NE, Roux E, Savineau JP, Marthan R. Effect of chronic hypoxia on calcium signalling in airway smooth muscle cells. Eur Respir J 1999; 14: 74–9.[Abstract]
- Roux E, Duvert M, Marthan R, Combined effect of chronic hypoxia an in vitro exposure to gas pollutants on airway reactivity. Am J Physiol (Lung Cell Mol Physiol) 2002; 283: L628–35.[Abstract/Free Full Text]
- Chen X, Yamakage M, Tsujiguchi N, et al. Interaction between volatile anesthetics and hypoxia in porcine tracheal smooth muscle. Anesth Analg 2000; 91: 996–1002.[Abstract/Free Full Text]
- Horowitz A, Menice CB, Laporte R, Morgan KG. Mechanisms of smooth muscle contraction. Physiol Rev 1996; 76: 967–1003.[Abstract/Free Full Text]
- Somlyo AP, Wu X, Walker LA, Somlyo AV. Pharmacomechanical coupling: the role of calcium, G-proteins, kinases and phosphatases. Rev Physiol Biochem Pharmacol 1999; 134: 201–34.[Medline]
- Lovren F, Triggle C. Nitric oxide and sodium nitroprusside-induced relaxation of the human umbilical artery. Br J Pharmacol 2000; 131: 521–9.[ISI][Medline]
- Mehr EH, Lindeman KS. Effect of halothane, propofol and thiopental on peripheral airway reactivity. Anesthesiology 1993; 79: 290–8.[ISI][Medline]
- Brown RH, Wagner EM. Mechanisms of bronchoprotection by anesthetic induction agents: propofol versus ketamine. Anesthesiology 1999; 90: 822–8.[ISI][Medline]
- Conti G, Dell’Utri D, Vilardi V, et al. Propofol induces bronchodilation in mechanically ventilated chronic obstructive pulmonary disease (COPD) patients. Acta Anaesthesiol Scand 1993; 37: 105–9.[ISI][Medline]
- Gin T, Gregory MA, Chan K, Oh TE. Maternal and fetal levels of propofol at caesarean section. Anaesth Intensive Care 1990; 18: 180–4.[ISI][Medline]
- Esener Z, Sarihasan B, Guven H, Ustun E. Thiopentone and etomidate concentrations in maternal and umbilical plasma, and in colostrum. Br J Anaesth 1992; 69: 586–8.[Abstract/Free Full Text]
- Gregory MA, Davidson DG. Plasma etomidate levels in mother and fetus. Anaesthesia 1991; 46: 716–8.[ISI][Medline]
- Roux E, Guibert C, Savineau JP, Marthan R. [Ca2+]i oscillations induced by muscarinic stimulation in airway smooth muscle cells: receptor subtypes and correlation with the mechanical activity. Br J Pharmacol 1997; 120: 1294–301.[ISI][Medline]
- Kai T, Bremerich DH, Jones KA, Warner DO. Drug-specific effects of volatile anesthetics on Ca2+ sensitization in airway smooth muscle. Anesth Analg 1998; 87: 425–9.[Abstract/Free Full Text]
- Hanazaki M, Jones KA, Warner DO. Effects of intravenous anesthetics on Ca2+ sensitivity in canine tracheal smooth muscle. Anesthesiology 2000; 92: 133–9.[ISI][Medline]
- Yamakage M, Chen X, Tsujiguchi N, et al. Different inhibitory effects of volatile anesthetics on T- and L-type voltage-dependent Ca2+ channels in porcine tracheal and bronchial smooth muscles. Anesthesiology 2001; 94: 683–93.[ISI][Medline]
- Belouchi NE, Roux E, Savineau JP, Marthan R. Interaction of extracellular albumin and intravenous anaesthetics, etomidate and propofol, on calcium signalling in rat airway smooth muscle cells. Fundam Clin Pharmacol 2000; 14: 395–400.[ISI][Medline]
Accepted for publication December 5, 2002.
This article has been cited by other articles:
|
|
|
|
 
M. Yamaguchi, O. Shibata, K. Nishioka, T. Makita, and K. Sumikawa
Propofol attenuates ovalbumin-induced smooth muscle contraction of the sensitized rat trachea: inhibition of serotonergic and cholinergic signaling.
Anesth. Analg.,
September 1, 2006;
103(3):
594 - 600.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
