Project: Research project

Project Details


The long-term goal of this research program is to continue to elucidate the
underlying mechanism for impaired pulmonary gas exchange during general
anesthesia. The specific goal of this project is to test the hypothesis
that anesthetic agents a ' erect pulmonary resistance by a number of
mechanisms. Pulmonary resistance is not only determined by the pressure
loss along the airways (airway resistance), but also to a large extent by
the pressure loss caused by the pressure-volume hysteresis of lung tissue
(tissue resistance). We propose to test the hypothesis that anesthetics
alter in humans both airway resistance and tissue resistance (specific aim
1). The tissue resistance could be altered by an effect of anesthetics on
the function of the surfactant, the smooth muscles of the airways or
alveolar ducts or a combination of these effects. If anesthetics had an
effect on alveolar duct smooth muscles, pulmonary gas exchange may be
affected, because the smooth muscles in the alveolar ducts may keep
alveolar septa tense. If anesthetics were to relax these fibers, previously
tense alveolar septa may slacken, thus decreasing the surface to volume
ratio in the lung. In specific aim 1 we will also determine whether N20 has
an effect on airway resistance. In specific aim 2 we will examine the
hypothesis that volatile anesthetics inhibit airway smooth muscle
constriction by reducing activity in nerves innervating the muscle, by
direct effects on the smooth muscle cell, and by effects on airway
epithelial function. This aim addresses two previously unappreciated but
important points. First, distinguishing between neurally-mediated and
direct effects of anesthetics on the airways is important because in vivo
airway smooth muscle may be constricted by both reflex and direct stimuli.
For example, laryngeal irritation caused by an endotracheal tube may
constrict the airways predominantly by a reflex mechanism. Conversely,
humoral mediators released in response to an immunologic stimulus or during
asthma may directly affect the airway smooth muscle cell. Secondly, if
anesthetics affect epithelial function, then the response of patients with
damaged airway epithelium (such as asthmatics) to volatile anesthetics may
be altered. In the third specific aim we will test the hypothesis that
injectable anesthetic agents attenuate hypocapnic bronchoconstriction in
dogs. Attenuation of the hypocapnic bronchoconstriction may result in a
loss of airway response to differences in regional P(CO2). This may cause
increased VA/Q mismatch during anesthesia. We wish to test our hypothesis
that injectable anesthetics may interfere less with hypocapnic
bronchoconstriction than volatile anesthetics.
Effective start/end date7/1/906/30/06


  • Medicine(all)