Altered thoracic gas compression contributes to improvement in spirometry with lung volume reduction surgery.

BACKGROUND: Thoracic gas compression (TGC) exerts a negative effect on forced expiratory flow. Lung resistance, effort during a forced expiratory manoeuvre, and absolute lung volume influence TGC. Lung volume reduction surgery (LVRS) reduces lung resistance and absolute lung volume. LVRS may therefore reduce TGC, and such a reduction might explain in part the improvement in forced expiratory flow with the surgery. A study was conducted to determine the effect of LVRS on TGC and the extent to which reduced TGC contributed to an improvement in forced expiratory volume in 1 second (FEV1) following LVRS. METHODS: The effect of LVRS on TGC was studied using prospectively collected lung mechanics data from 27 subjects with severe emphysema. Several parameters including FEV1, expiratory and inspiratory lung resistance (Rle and Rli), and lung volumes were measured at baseline and 6 months after surgery. Effort during the forced manoeuvre was measured using transpulmonary pressure. A novel method was used to estimate FEV1 corrected for the effect of TGC. RESULTS: At baseline the FEV1 corrected for gas compression (NFEV1) was significantly higher than FEV1 (p<0.0001). FEV1 increased significantly from baseline (p<0.005) while NFEV1 did not change following surgery (p>0.15). TGC decreased significantly with LVRS (p<0.05). Rle and maximum transpulmonary pressure (TP(peak)) during the forced manoeuvre significantly predicted the reduction in TGC following the surgery (Rle: p<0.01; TP(peak): p<0.0001; adjusted R2 = 0.68). The improvement in FEV1 was associated with the reduction in TGC after surgery (p<0.0001, adjusted R2 = 0.58). CONCLUSIONS: LVRS decreased TGC by improving expiratory flow limitation. In turn, the reduction in TGC decreased its negative effect on expiratory flow and therefore explained, in part, the improvement in FEV1 with LVRS in this cohort.

Respiratory control during independent lung ventilation.

We describe the case of a lung transplant patient with primary graft failure and an emphysematous native lung, who displayed different respiratory rates between the transplanted lung and the native lung. Inflation of the native lung delayed the next inspiratory effort relative to inflation of the denervated transplanted lung. Synchronous inflation of both lungs required more pressure in each lung than when that lung was inflated with the contralateral lung near functional residual capacity, suggesting the two lungs compete for space within the thoracic cavity.

Effects of smooth muscle activation on axial mechanical properties of excised canine bronchi.

This study tested the hypothesis that airway smooth muscle (ASM) activation produces an airway active axial force (AAAF). Bronchi (n = 10) immersed in a tissue bath containing 95% O2-5% CO2-equilibrated Krebs solution were subjected to passive axial lengthening and shortening at 0-20 cmH2O of transmural pressure. ASM was relaxed with isoproterenol and activated with methacholine. Axial tensile (epsilonx), transverse compressive (epsilony), and shear strains (epsilonxy) were computed from the displacements of four markers placed onto the specimen's surface. The AAAF was estimated by subtracting the control axial force (AF) values at a given epsilonx from those obtained after methacholine. epsilonx-AF relationships were curvilinear, with maximum epsilonx being approached at approximately 15 g of AF. The epsilony decreased during bronchial lengthening. Cholinergic stimulation produced 1) a decrease of both epsilonx and epsilony at a given AF relative to control, indicating ASM shortening, and 2) an AAAF that increased with increasing epsilonx and transmural pressure. A portion of the work of expanding the lungs is required to lengthen the airways; therefore, an AAAF would increase lung elastance and recoil.

Desmin integrates the three-dimensional mechanical properties of muscles.

Striated muscle is a linear motor whose properties have been defined in terms of uniaxial structures. The question addressed here is what contribution is made to the properties of this motor by extramyofilament cytoskeletal structures that are not aligned in parallel with the myofilaments. This question arose from observations that transverse loads increase muscle force production in diaphragm but not in the hindlimb muscle, thereby indicating the presence of structures that couple longitudinal and transverse properties of diaphragmatic muscle. Furthermore, we find that the diaphragms of null mutants for the cytoskeletal protein desmin show 1) significant reductions in coupling between the longitudinal and transverse properties, indicating for the first time a role for a specific protein in integrating the three-dimensional mechanical properties of muscle, 2) significant reductions in the stiffness and viscoelasticity of muscle, and 3) significant increases in tetanic force production. Thus desmin serves a complex mechanical function in diaphragm muscle by contributing both to passive stiffness and viscoelasticity and to modulation of active force production in a three-dimensional structural network. Our finding changes the paradigm of force transmission among cells by placing our understanding of the function of the cytoskeleton in the context of the structural and mechanical complexity of muscles.

Measurement of pulmonary resistance and dynamic compliance with airway obstruction.

We compared four algorithms by using least squares regression for determination of pulmonary resistance and dynamic elastance in subjects with emphysema, normal subjects, and subjects with asthma before and after bronchoconstriction. The four methods evaluated include 1) a single resistance and elastance, 2) separate resistances and elastances for each half breath, 3) separate inspiratory and expiratory resistances with a single elastance, and 4) separate inspiratory and expiratory resistances, an expiratory volume interaction term, and a single elastance. All methods gave comparable results in normal and asthmatic subjects. We found expiratory resistance was larger than inspiratory resistance in normal and asthmatic subjects during control conditions, but inspiratory resistance was higher than expiratory resistance in subjects who experienced severe bronchoconstriction in response to methacholine. In subjects who are flow limited, method 2 gives a higher inspiratory resistance than would be computed by assuming that the elastic pressure-volume curve passes through the zero-flow points. Methods 1 and 3 overestimate dynamic elastance and inspiratory resistance. Method 4 appears to identify flow limitation and dynamic hyperinflation and gives a good measure of inspiratory resistance and dynamic elastance.

An electronic circuit simulating T-type calcium-channel current from the sinoatrial node.

A circuit that simulates T-type calcium-channel current characteristics of the sinoatrial (SA) node was developed from discrete electronic components and tested at physiologic membrane voltage ranges. The circuit design was based on the T-type calcium-channel current dynamics obtained from a mathematical model of the SA node membrane, which, in turn, is based on physiologic data. The design was held at a resting membrane potential and then stepped to new voltages over the entire operating range of the T-type calcium channel. The circuit was validated by comparing its transient response current with the predicted current from the mathematical model. In addition, the peak currents of the circuit were compared with plots of peak current obtained from the mathematical model and physiologic data. By showing that the electronic circuit mimics the T-type calcium-channel current dynamics found within the SA node, the results may provide a foundation for developing a novel cardiac pacemaker that is based on the ion-channel characteristics of excitable tissue.

Single channel evidence for a cytoskeletal defect involving acetylcholine receptors and calcium influx in cultured dystrophic (mdx) myotubes.

Single channel events that exhibited the conductance, event duration, and ion selectivity characteristics of calcium leakage activity (CLA) were recorded in association with acetylcholine receptor (AChR) activity in cultured nondystrophic myotubes. The CLA was observed in the presence or absence of acetylcholine (ACh), and at normal or elevated concentrations of calcium. In contrast to results from nondystrophic myotubes, cell-attached patches from several cultured dystrophic (mdx) myotubes exhibited 100% CLA with no AChR activity, even though ACh was present in the pipette solution. Acquisition of an inside-out patch from these membrane areas produced a profound decrease in CLA and the appearance of AChR events exhibiting typical conductance and event duration characteristics. These results suggest that CLA in dystrophic muscle is produced, in part, by unusual physical interactions between AChRs and the dystrophic cytoskeleton that are mediated by the action of intracellular modulators responsible for aggregating and stabilizing AChRs.

A microprocessor controlled page turner.

The Page-A-R.A.M.A. (Remote Automated Manuscript Advance) was designed and constructed to turn a single page of a standard sized book. The design is intended to fulfill the needs of a handicapped user who cannot turn the pages of a book. The user starts the procedure by triggering a switch, that produces a TURN PAGE command. After a TURN PAGE command has been indicated, a DC gearmotor turns a page through a driver arm and suction device. When the page is attached to the arm, the gearmotor reverses, and lifts the page from the book. When the page reaches a certain height, a blower is activated and the suction device is detached from the page, allowing the page to be turned to the other side of the book. The above process is controlled by a Motorola 68HC11 microprocessor. Since this will be a single unit production the microprocessor evaluation board, MC68HC11EVB, was used. Construction of the Page-A-R.A.M.A. is not fully completed. The initial testing shows that the suction/blower device does turn pages. A problem exists because of static electricity between the book pages, causing the suction device to pick up more than one page at a time. A possible solution for the problem is treating the book by chemical means to eliminate the static electricity. Further testing and refinements will be performed on the Page-A-R.A.M.A.