GROUP III AND IV MUSCLE AFFERENTS ARE RESPONSIVE TO ISCHEMIA IN THE EXERCISING CAT

Although many types of reflex receptors affecting cardiopulmonary function during exercise will respond to isolated stimuli or pharmacological cocktails, it is often difficult to discern their physiological relevance. Adreani and Kaufman (p. 1827) have accomplished this difficult task by measuring group III and IV afferent activity from contracting limb muscles in decerebrate cats made to locomote via electrical stimulation of the mesencephalic locomotor region. They have superimposed muscle ischemia on dynamic exercise and have shown that many group III and IV afferents increase their responsiveness and that this enhanced response is not explained by increased hydrogen ion or lactate, as measured in the effluent blood from the working muscle. These results enhance the understanding of the responsiveness of these receptors to physiological stimuli in exercising muscle. The paper is discussed in an Invited Editorial by Thomas et al. (p. 1825).

	GENDER DIFFERENCES IN REGIONAL DEPOSITION OF INHALED PARTICLES

Kim and Hu (p. 1834) compared differences in regional deposition patterns between healthy male and female subjects by using a serial aerosol bolus technique. Local deposition fraction was defined in ten local volumetric regions of the lung. All subjects showed an uneven deposition distribution pattern with characteristic unimodal curves that depended on particle size and flow rate. However, in women the unevenness was greater for fine aerosols (1 µm in diameter), and the local deposition fraction of coarse particles (3 and 5 µm in diameter) was enhanced in the proximal regions. Total lung deposition was comparable in men and women, but in women coarse particle deposition was greater at all flow rates and the increase was greater at high flow rates.

	GLUTAMINE AND ALANINE RELEASE FROM MUSCLE AFTER EXERCISE

Ammonia is formed in working skeletal muscle. The appearance of this potentially toxic species can be beneficial if its clearance is linked to formation of the major gluconeogenic precursors, glutamine and alanine. Galassetti et al. (p. 1952) asked whether glucose feeding could stimulate release of glutamine and alanine after exercise, thereby promoting muscle recovery. The investigators utilized instrumented dogs and provided glucose via intraduodenal infusion while measuring glutamine and alanine efflux from hindlimb muscle after exercise. Results show enhanced release of the gluconeogenic amino acids and indicate yet another beneficial effect of providing carbohydrate nutrition soon after exercise.

	EXERTIONAL DYSPNEA IN PATIENTS WITH INTERSTITIAL LUNG DISEASE

Interstitial lung disease frequently causes dyspnea and exercise intolerance, which progress inexorably as the disease advances. The factors responsible for dyspnea in this setting are unknown. O'Donnell et al. (p. 2000) compared dyspnea, ventilation, breathing pattern, operational lung volume, and esophageal pressures during exercise in patients and age-matched controls. Patients experienced greater dyspnea intensity, lower tidal volume, and higher esophageal pressure-to-tidal volume ratio than did control subjects. Within the patient group, dyspnea correlated strongly with tidal volume-to-inspiratory capacity ratio but not with esophageal pressure indexes. These results suggest that dyspnea in patients with interstitial lung disease may somehow arise from a mismatch between respiratory effort and thoracic displacement at times when ventilatory demand is increased.

	HYPOXIA AND HETEROGENEITY OF PULMONARY BLOOD FLOW

The advent of fluorescent-labeled microspheres for measuring regional blood flow with high resolution has lead to a flurry of activity in the field of pulmonary blood flow distribution. One observation has been that pulmonary blood flow is quite heterogeneous, and a large fraction of the heterogeneity cannot be accounted for by gravity alone. Mann et al. (p. 2010) investigated the impact of one-lung hypoxia on the between-lungs and within-lung distribution of flow in anesthetized dogs. Given that hypoxia is a mechanism for making local perfusion more even relative to local ventilation, they wondered what the effect of regional hypoxia on interregional perfusion heterogeneity would be. They found paradoxically that perfusion within the hypoxic region became more heterogeneous. The mechanism responsible has not been revealed.

	ARE COUGHING AND BREATHING GENERATED BY THE SAME NEURAL NETWORK?

The movement of air generated by respiratory muscles subserves not only ventilation but also important reflexes such as cough, which help maintain lung function and airway patency. Are the motor patterns for ventilation and cough subserved by the same brain stem neural networks? Shannon and colleagues (p. 2020) combine in vivo studies in cats with a computer-simulated model for cough. Their overall conclusion is that both ventilation and cough utilize the same brain stem circuits, organized appropriately for each movement. Of interest is that their initial model made sufficiently specific and testable predictions that they were able to delineate its shortfalls and propose a revised, testable model.

	DISSECTING THE COMPONENTS OF THE PULMONARY DIFFUSING CAPACITY

CO (and O₂) transport between alveolar gas and the red blood cells in the lung capillary occurs via diffusion and ends in a chemical reaction with the gas binding to hemoglobin. Physiologists have long asked how much of the time to equilibration of CO (or O₂) is due to diffusion and how much is due to this chemical reaction. By assuming that NO has an infinitely rapid "chemical reaction" with hemoglobin and by simultaneously measuring NO and CO diffusing capacities, Heller and Schuster (p. 2066) show that ~40% of the transport resistance is due to chemical reaction. How much does this actually impede the transport process? Theoretical considerations for O₂ suggest that the greatest impedance occurs when diffusing capacity is high (but where complete equilibration is reached). When diffusing capacity is reduced, the reaction rate is less important, since diffusion resistance dominates total resistance.

	GAS EXCHANGE IN CONDUCTING AIRWAYS

Pulmonary gas exchange is generally considered to occur in the alveoli, and end-tidal gas concentrations normally approximate those of arterial blood. The conducting airways, the "anatomic dead space," are just that: transport plumbing that plays no role in gas exchange. Recent evidence suggests that for extremely soluble gases, such as ethanol, this view is incorrect. Bui et al. (p. 2070) add to this evidence with a mathematical model, which indicates that the bronchial circulation delivers sufficient ethanol to the airway epithelial surface to account for about one-half of the ethanol exhaled. The remainder presumably emanates as expected from the alveolar region. These findings may have practical significance in the conduct and interpretation of "Breathalyzer" tests.

	ACTIONS OF NICOTINE ON PULMONARY ENDOTHELIAL CELLS

Cigarette smoking is associated with increased risk of developing lung cancer and cardiovascular disease. To explore the hypothesis that these effects may be mediated by actions of nicotine on vascular endothelial cells, Villablanca (p. 2089) examined the effects of nicotine on DNA synthesis, DNA repair, and proliferation and cytotoxicity in cultured bovine pulmonary endothelial cells. Nicotine stimulated endothelial cell DNA synthesis and proliferation, even at concentrations lower than those reported in the blood of smokers. These effects were enhanced by serum and platelet-derived endothelial growth factors. Higher concentrations of nicotine produced cytotoxicity. These results indicate that nicotine can modulate endothelial cell growth and suggest that understanding these effects may be important to understanding tumor angiogenesis, endothelial toxicity, and related vascular dysfunction in smokers.