To investigate the hypothesis that altered Ca2+ signaling in airway smooth muscle cells (SMCs) is responsible for airway hyperreactivity, we compared, with the use of confocal and phase-contrast microscopy, the airway contractility and Ca2+ changes in SMCs induced by acetylcholine (ACh) in lung slices from different mouse strains (A/J, Balb/C, and C3H/ HeJ). The airways from each mouse strain displayed a concentration-dependent contraction to ACh. The contractile response of the airways of the C3H/HeJ mice was found, in contrast to earlier studies, to be much greater and faster than that of A/J and Balb/C mice. This difference in airway reactivity can be, in part, attributable to halothane, a volatile anesthetic that was previously used during in vivo measurements of airway reactivity but found here to significantly alter the ACh contractile response of airways in lung slices. The ACh-induced Ca2+ response of the airway SMCs in all of the various mouse strains was also concentration dependent. The magnitude of the initial Ca2+ increase and the frequency of the subsequent Ca2+ oscillations induced by ACh increased with ACh concentration. However, no differences in the Ca2+ responses to ACh could be distinguished between the mouse strains. These results suggest that the mechanism responsible for airway hyperreactivity in different mouse strains resides with the Ca2+ sensitivity of the contractile apparatus of the SMCs rather than with the Ca2+ signaling itself.

We postulated that nitrous oxide transfer into the pleural cavity can occur by diffusion from the alveoli, independent of vascular transport. Under general anaesthesia, six sheep were studied in two phases, a control and an experimental phase. The sheep were anaesthetized, intubated, and received positive pressure mechanical ventilation. A catheter was placed in the right pleural cavity and 150 ml air injected. The animals were ventilated with 100% oxygen. The inspired gas was changed to a mixture of 50% nitrous oxide and 50% oxygen, and the rate of increase of nitrous oxide concentration in the pleural space was measured. The animals were then ventilated with 100% oxygen and then killed by exsanguination while ventilation was continued. The inspired mixture was changed to 50% nitrous oxide and 50% oxygen and the rate of increase in nitrous oxide concentration was measured in the pleural space again. During venitilation with nitrous oxide in the living animals, the concentration of nitrous oxide in the pleural cavity increased rapidly and decreased to zero during ventilation with 100% oxygen. During ventilation without circulation, the rate of increase in the concentration of nitrous oxide in the pleural cavity was the same as in the control phase. This suggests that nitrous oxide enters the pleural space by diffusion, rather than by vascular delivery. This mechanism may explain the rapid increase in the volume of pneumothorax if nitrous oxide is given in the inspired gas.

BACKGROUND: Children with severe bronchospasm requiring mechanical ventilation may become refractory to conventional therapy. In these critically ill patients, isoflurane is an inhaled anesthetic agent available in some centers to treat bronchospasm. We hypothesized that isoflurane is safe and would lead to improved gas exchange in children with life-threatening bronchospasm refractory to conventional therapy. METHODS: A retrospective review was conducted and included mechanically ventilated children treated with isoflurane in a quaternary pediatric ICU for life-threatening bronchospasm, from 1993 to 2007. Demographic, blood gas, ventilator, and outcome data were collected. RESULTS: Thirty-one patients, with a mean age of 9.5 years (range 0.4-23 years) were treated with isoflurane, from 1993 to 2007. Mean time to initiation of isoflurane after intubation was 13 hours (0-120 h), and the mean maximum isoflurane dose was 1.1% (0.3-2.5%). Mean duration of isoflurane administration was 54.5 hours (range 1-181 h), with a total mean duration of mechanical ventilation of 252 hours (range 16-1,444 h). Isoflurane led to significant improvement in pH and P(CO(2)) within 4 hours of initiation (P ≤ .001). Complications during isoflurane administration included hypotension requiring vasoactive infusions in 24 (77%), arrhythmia in 3 (10%), neurologic side effects in 3 (10%), and pneumothorax in 1 (3%) patient. CONCLUSIONS: Isoflurane led to improvement in pH and P(CO(2)) within 4 hours in this series of mechanically ventilated patients with life-threatening bronchospasm. The majority of patients in this series developed hypotension, but there was a low incidence of other side effects related to isoflurane administration. Isoflurane appears to be an effective therapy in patients with life-threatening bronchospasm refractory to conventional therapy. However, further investigation is warranted, given the uncertain overall impact of isoflurane in this context.