Anesthetics Inhibit Acetylcholine-promoted Guanine Nucleotide Exchange of Heterotrimeric G Proteins of Airway Smooth Muscle

Background: Anesthetics inhibit airway smooth muscle contraction in part by a direct effect on the smooth muscle cell. This study tested the hypothesis that the anesthetics halothane and hexanol, which both relax airway smooth muscle in vitro, inhibit acetylcholine-promoted nucleotide exchange at the [alpha] subunit of the Gq/11 heterotrimeric G protein (G[alpha]q/11; i.e., they inhibit muscarinic receptor-G[alpha]q/11 coupling).

Methods: The effect of halothane (0.38 +/- 0.02 mm) and hexanol (10 mm) on basal and acetylcholine-stimulated G[alpha]q/11 guanosine nucleotide exchange was determined in membranes prepared from porcine tracheal smooth muscle. The nonhydrolyzable, radioactive form of guanosine-5'-triphosphate, [35S]GTP[gamma]S, was used as the reporter for G[alpha]q/11 subunit dissociation from the membrane to soluble fraction, which was immunoprecipitated with rabbit polyclonal anti-G[alpha]q/11 antiserum.

Results: Acetylcholine caused a significant time- and concentration-dependent increase in the magnitude of G[alpha]q/11 nucleotide exchange compared with basal values (i.e., without acetylcholine), reaching a maximal difference at 100 [mu]m (35.9 +/- 2.9 vs. 9.8 +/- 1.2 fmol/mg protein, respectively). Whereas neither anesthetic had an effect on basal G[alpha]q/11 nucleotide exchange, both halothane and hexanol significantly inhibited the increase in G[alpha]q/11 nucleotide exchange produced by 30 [mu]m acetylcholine (by 59% and 68%, respectively).     

Cine CT for attenuation correction in cardiac PET/CT.

In dual-modality PET/CT systems, the CT scan provides the attenuation map for PET attenuation correction. The current clinical practice of obtaining a single helical CT scan provides only a snapshot of the respiratory cycle, whereas PET occurs over multiple respiratory cycles. Misalignment of the attenuation map and emission image because of respiratory motion causes errors in the attenuation correction factors and artifacts in the attenuation-corrected PET image. To rectify this problem, we evaluated the use of cine CT, which acquires multiple low-dose CT images during a respiratory cycle. We evaluated the average and the intensity-maximum image of cine CT for cardiac PET attenuation correction. METHODS: Cine CT data and cardiac PET data were acquired from a cardiac phantom and from multiple patient studies. The conventional helical CT, cine CT, and PET data of an axially translating phantom were evaluated with and without respiratory motion. For the patient studies, we acquired 2 cine CT studies for each PET acquisition in a rest-stress (13)N-ammonia protocol. Three readers visually evaluated the alignment of 74 attenuation image sets versus the corresponding emission image and determined whether the alignment provided acceptable or unacceptable attenuation-corrected PET images. RESULTS: In the phantom study, the attenuation correction from helical CT caused a major artifactual defect in the lateral wall on the PET image. The attenuation correction from the average and from the intensity-maximum cine CT images reduced the defect by 20% and 60%, respectively. In the patient studies, 77% of the cases using the average of the cine CT images had acceptable alignment and 88% of the cases using the intensity maximum of the cine CT images had acceptable alignment. CONCLUSION: Cine CT offers an alternative to helical CT for compensating for respiratory motion in the attenuation correction of cardiac PET studies. Phantom studies suggest that the average and the intensity maximum of the cine CT images can reduce potential respiration-induced misalignment errors in attenuation correction. Patient studies reveal that cine CT provides acceptable alignment in most cases and suggest that the intensity-maximum cine image offers a more robust alternative to the average cine image.