The protective effects of volatile anesthestics against the bronchoconstriction induced by an allergic reaction in sensitized rabbit pups.

BACKGROUND: Volatile inhaled anesthetics exert a differential protective effect against bronchospasm development after cholinergic stimulation. However, their ability to inhibit the adverse respiratory consequences of an anaphylactic reaction after exposure to an allergen has not been characterized. We therefore compared the abilities of isoflurane, sevoflurane, and desflurane to prevent the lung constriction induced by an allergic reaction in a pediatric model of an anaphylactic reaction. METHODS: Low-frequency respiratory input impedance (Zrs) was measured in 4 groups of ovalbumin (OVA)-sensitized 5-week-old rabbit pups anesthetized with midazolam (group IV) and with inhaled isoflurane (group ISO), sevoflurane (group SEVO), or desflurane (group DES) at 1 minimum alveolar concentration. Zrs was measured under baseline conditions and after an anaphylactic lung response provoked by IV allergen injection (OVA 1 mg), during which the changes in airway resistance (Raw), tissue damping (G), and elastance obtained from Zrs were followed for 15 minutes. RESULTS: Allergen provocation generated immediate severe bronchoconstriction, with no statistically significant difference in Raw increase among the groups in the first 3 minutes. Conversely, the inhalation of volatile anesthetics accelerated the recovery from the allergen-induced bronchoconstriction, particularly in group SEVO where the Raw was significantly lower than that in group IV 4 minutes after the allergen challenge. These changes were paralleled by significant elevations in G in all groups, with a significantly more pronounced deterioration in the animals in group DES. The anesthetic regimen did not statistically significantly affect the sustained increases in elastance after OVA injections. CONCLUSIONS: Our results reveal the lack of potential of the commonly used volatile anesthetics to inhibit the most severe acute phase of the constrictor response to allergen after anaphylaxis in both the central airway and peripheral lung compartments. Inhalation of volatile anesthetics, particularly sevoflurane, promotes an earlier easing of the bronchospasm; this beneficial profile may be advantageous in children with atopic lung diseases.

Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats.

BACKGROUND: The effectiveness of strategies for treatment of the altered static lung volume and against the development of bronchial hyperreactivity (BHR) following a left ventricular dysfunction (LVD) induced by myocardial ischaemia was investigated in a rat model of sustained postcapillary pulmonary hypertension. METHODS: Airway resistance (Raw) was identified from the respiratory system input impedance (Zrs) in four groups of rats. End-expiratory lung volume (EELV) was determined plethysmographically, and Zrs was measured under baseline conditions and following iv infusions of 2, 6 or 18 µg/kg/min methacholine. Sham surgery was performed in the rats in Group C, while the left interventricular coronary artery was ligated and Zrs and its changes following identical methacholine challenges were reassessed in the same rats 8 weeks later, during which no treatment was applied (Group I), or the animals were treated daily with a combination of an angiotensin enzyme converter inhibitor and a diuretic (enalapril and furosemide, Group IE), or a calcium channel blocker (diltiazem, Group ID). The equivalent dose of methacholine causing a 100% increase in Raw (ED50) was determined in each group. Diastolic pulmonary arterial pressure (PapD) was assessed by introducing a catheter into the pulmonary artery. RESULTS: The sustained presence of a LVD increased PapD in all groups of rats, with variable but significant elevations in Groups I (p=0.004), ID (p=0.013) and IE (p=0.006). A LVD for 8 weeks induced no changes in baseline Raw but elevated the EELV independently of the treatments. In Group I, BHR consistently developed following the LVD, with a significant decrease in ED50 from 10.0 ± 2.5 to 6.9 ± 2.5 µg/kg/min (p=0.006). The BHR was completely abolished in both Groups ID and IE, with no changes in ED50 (9.5 ± 3.6 vs. 10.7 ± 4.7, p=0.33 and 10.6 ± 2.1 vs. 9.8 ± 3.5 µg/kg/min p=0.56, respectively). CONCLUSIONS: These findings suggest that a LVD following coronary ischaemia consistently induces BHR. The more consistent efficacy of both treatment strategies in preventing BHR than in treating the adverse pulmonary vascular consequences suggests the benefit of both calcium channel blockade and ACE inhibition to counteract the airway susceptibility following a LVD.

Bronchoconstriction during alveolar hypocapnia and systemic hypercapnia in dogs with a cardiopulmonary bypass.

The roles of the alveolar and systemic CO2 on the lung mechanics were investigated in dogs subjected to cardiopulmonary bypass. Low-frequency pulmonary impedance data (Z(L)) were collected in open-chest dogs with an alveolar CO2 level (FA(CO2)) of 0.2-7% and during systemic hypercapnia before and after elimination of the vagal tone. Airway resistance (R(aw)), inertance (I(aw)), parenchymal damping (G) and elastance (H) were estimated from the Z(L). The highest R(aw) observed at 0.2% FA(CO2),which decreased markedly up to a FA(CO2) of 2% (212 ± 24%), and remained unchanged under normo- and hypercapnia (FA(CO2) 2-7%). These changes were associated with smaller decreases in I(aw) (-16.6 ± 3.7%), mild elevations in G (25.7 ± 4.7%), and no change in H. Significant increases in all mechanical parameters were observed following systemic hypercapnia; atropine counteracted the R(aw) rises. We conclude that severe alveolar hypocapnia may contribute to minimization of the ventilation-perfusion mismatch by constricting the airways in poorly perfused lung regions. The constrictor potential of systemic hypercapnia is mediated by vagal reflexes.

Lung mechanical and vascular changes during positive- and negative-pressure lung inflations: importance of reference pressures in the pulmonary vasculature.

The continuous changes in lung mechanics were related to those in pulmonary vascular resistance (Rv) during lung inflations to clarify the mechanical changes in the bronchoalveolar system and the pulmonary vasculature. Rv and low-frequency lung impedance data (Zl) were measured continuously in isolated, perfused rat lungs during 2-min inflation-deflation maneuvers between transpulmonary pressures of 2.5 and 22 cmH(2)O, both by applying positive pressure at the trachea and by generating negative pressure around the lungs in a closed box. ZL was averaged and evaluated for 2-s time windows; airway resistance (Raw), parenchymal damping and elastance (H) were determined in each window. Lung inflation with positive and negative pressures led to very similar changes in lung mechanics, with maximum decreases in Raw [-68 +/- 4 (SE) vs. -64 +/- 18%] and maximum increases in H (379 +/- 36 vs. 348 +/- 37%). Rv, however, increased with positive inflation pressure (15 +/- 1%), whereas it exhibited mild decreases during negative-pressure expansions (-3 +/- 0.3%). These results demonstrate that pulmonary mechanical changes are not affected by the opposing modes of lung inflations and confirm the importance of relating the pulmonary vascular pressures in interpreting changes in Rv.

The involvement of histaminic and muscarinic receptors in the bronchoconstriction induced by myorelaxant administration in sensitized rabbits.

BACKGROUND: Muscle relaxants cause bronchospasm via histamine release and/or by acting on the muscarinic receptors; we sought to characterize the respective importance of these pathways in the presence of bronchial hyperreactivity. METHODS: Ovalbumin-sensitized rabbits were randomly assigned to several protocol groups: Group C comprised untreated animals; in the other three groups, either H1 and H2 histaminic receptor blockade was performed, leaving the M1, M2, and M3 muscarinic receptors functional (Group M123), or combining this treatment with M3 muscarinic receptor blockade (Group M12), or with vagotomy (Group M3). Respiratory system impedance was measured over a 90-s period, during which succinylcholine, mivacurium or atracurium was administered. To monitor the changes in lung mechanics, respiratory system impedance was averaged in a 2-s time window and fitted by a model featuring airway resistance and inertance and tissue damping and elastance. RESULTS: The peak increases in airway resistance in Group C were greatest with succinylcholine (79 +/- 17[SE]%) and mivacurium administration (75% +/- 12%), whereas they were lower after attracurium (40% +/- 11%). These changes were markedly attenuated by both histamine and muscarinic receptor blockade with the largest reduction in Group M3 for succinylcholine (14% +/- 5.2%), and in Group M123 for mivacurium (5.1% +/- 9.1%) and attracurium (7.8% +/- 4.0%). DISCUSSION: Although the bronchospasm developing in the allergic airways after muscle relaxants is mediated primarily by the histaminic pathway, the interactions of succinylcholine on the M1, M2, and M3 receptors, those of atracurium on the M1 and M2 receptors, and those of mivacurium on the M3 receptors may also play a role.

The role of endothelin-1 in hyperoxia-induced lung injury in mice.

BACKGROUND: As prolonged hyperoxia induces extensive lung tissue damage, we set out to investigate the involvement of endothelin-1 (ET-1) receptors in these adverse changes. METHODS: Experiments were performed on four groups of mice: control animals kept in room air and a group of mice exposed to hyperoxia for 60 h were not subjected to ET-1 receptor blockade, whereas the dual ETA/ETB-receptor blocker tezosantan (TEZ) was administered via an intraperitoneal pump (10 mg/kg/day for 6 days) to other groups of normal and hyperoxic mice. The respiratory system impedance (Zrs) was measured by means of forced oscillations in the anesthetized, paralyzed and mechanically ventilated mice before and after the iv injection of ET-1 (2 microg). Changes in the airway resistance (Raw) and in the tissue damping (G) and elastance (H) of a constant-phase tissue compartment were identified from Zrs by model fitting. RESULTS: The plasma ET-1 level increased in the mice exposed to hyperoxia (3.3 +/- 1.6 pg/ml) relative to those exposed to room air (1.6 +/- 0.3 pg/ml, p < 0.05). TEZ administration prevented the hyperoxia-induced increases in G (13.1 +/- 1.7 vs. 9.6 +/- 0.3 cmH2O/l, p < 0.05) and H (59 +/- 9 vs. 41 +/- 5 cmH2O/l, p < 0.05) and inhibited the lung responses to ET-1. Hyperoxia decreased the reactivity of the airways to ET-1, whereas it elevated the reactivity of the tissues. CONCLUSION: These findings substantiate the involvement of the ET-1 receptors in the physiopathogenesis of hyperoxia-induced lung damage. Dual ET-1 receptor antagonism may well be of value in the prevention of hyperoxia-induced parenchymal damage.