DOES LACTATE ION STIMULATE BREATHING?

During heavy exercise, lactic acid accumulates in arterial blood, and ventilation rises more than in proportion to the CO₂ production rate, resulting in alveolar and arterial hypocapnia. Hardarson et al. (p. 411) examined the possibility that this exertional hyperventilation reflects a specific response to lactate ion rather than to acidity by infusing a lactic acid-sodium lactate combination in anesthetized rats. This treatment resulted in a large increase in arterial lactate concentration, with no change in pH. Ventilation increased, but arterial PCO₂ remained unchanged, reflecting an increase in CO₂ production from lactate oxidation. Thus the ventilatory stimulation may represent a response to either lactate ion or CO₂ production. The paper is discussed in an Invited Editorial by Fregosi (p. 409).

	A SELECTIVE PULMONARY VASODILATOR?

Vasodilator therapy is effective in treating certain forms of pulmonary hypertension, but most effective pulmonary vasodilators also cause systemic vasodilation, which severely limits their usefulness. Thus pulmonary selectivity is the Holy Grail of pulmonary vasodilator therapy. Inhaled nitric oxide (NO) has the advantage that its effects are not transmitted to the systemic circulation because the NO is inactivated rapidly when it reaches the blood. However, the NO needs to be supplied continuously, which is difficult and cumbersome. Adrie et al. (p. 435) proposed the administration of an NO donor, 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA), in an aerosol as an alternative having pulmonary selectivity while allowing for intermittent administration. However, the authors found that doses that produced pulmonary vasodilation equivalent to a given dose of inhaled NO also produced the undesirable systemic vasodilation not seen with the inhaled NO. Aerosolized nitroprusside had better selectivity than DEA but was not competitive with NO itself.

	CARDIOVASCULAR RESPONSES TO NECK FLEXION

Many postural adjustments, such as standing up, produce cardiovascular responses. Simple neck movements in mammals, including humans, increase muscle sympathetic nerve activity. Ray and Hume (p. 450) tested the obligatory involvement of the vestibular system in this reflex in humans by determining whether head movements that excite muscle receptors, but not vestibular receptors, produce changes in cardiovascular function. They observed only a slight increase in blood pressure but no change in sympathetic activity, suggesting that head movements produce their effects on blood flow via a vestibulosympathetic reflex.

	RAT "MINI-GYM" AND CANCELLOUS BONE ADAPTATION

Laboratory rats readily run on motorized treadmills, and this fact has allowed exercise physiologists and biochemists to use the rat as a model for physiological adaptation to endurance training. However, getting rats to perform resistance exercise has not been so easy. Using an ingenious cage setup, involving preconditioning rats to reach up and move a lever to avoid a mild electric shock, Westerlind and colleagues (p. 459) created a rat "mini-gym," which induced hindlimb resistance exercise as "squats." Then, over a period of 6 wk, the investigators gradually added weights to a vest in a resistance training group, whereas a control group performed without added weight. Results indicate no differences in cortical bone, but many parameters of cancellous bone responded positively to resistance training. Furthermore, osteocalcin mRNA was greatly increased over levels shown in control animals. The training model and its results represent novel approaches to studying long-standing problems. Get your bones to the gym!

	EATING AND DAYTIME SLEEPINESS

Postprandial sleepiness is a common experience, but understanding its cause is complicated by factors related to the circadian rhythm. Wells et al. (p. 507) attempted to identify a noncircadian contribution of food ingestion to sleepiness in normal subjects. Sleepiness, assessed by multiple sleep-latency testing, was greater 1.5 h after meals than before eating. The effect of circadian factors was studied in a subgroup of subjects whose mealtime was displaced by 2 h. The results reveal a meal-induced enhancement of sleepiness, part of which is independent of the circadian rhythm.

	PARTITIONING OF RESPIRATORY IMPEDANCE

Peslin and Duvivier (p. 553) devised a method that combined forced oscillations at the mouth with body plethysmography to separate airway from tissue impedance in human subjects. Alveolar gas compression was measured by body plethysmography, and alveolar gas compliance was derived from thoracic gas volume. Impedance was calculated by using the monoalveolar T-network model. Results verified previous studies: airway resistance increased while tissue resistance decreased with frequency. Airway reactance was dominated by an inertance and tissue reactance by an elastance. The partitioning was independent of mechanical inhomogeneity and only moderately affected by airway wall shunting.

	TRAINING BUILDS PLASMA PROTEIN, TOO

Plasma volume expansion leading to increased blood volume occurs in response to endurance training. This hypervolemia is isotonic and involves increased intravascular protein content, most of which is albumin. Because the source of the added albumin is unknown, Yang et al. (p. 584) used primed continuous infusions of [¹³C]phenylalanine to estimate fractional and absolute albumin synthesis rates immediately after a single exercise bout. These rates increased 6 and 16%, respectively, over the immediate 6-h postexercise period and could not completely account for the observed expansion of plasma volume. Thus some other mechanism, such as increased lymphatic return of albumin, must have contributed to the immediate expansion of plasma volume. However, if the measured increase in albumin synthesis persisted over the next 18 h of recovery, it could account for the increase in plasma albumin content at 24 h.

	ESTIMATING THE MEMBRANE COMPONENT OF THE PULMONARY DIFFUSING CAPACITY

The conventional measurement of the diffusing capacity of the alveolar-capillary membrane by using carbon monoxide (Dm_CO) yields values one-tenth of those predicted from morphometric studies. Two novel indicator gases for estimating Dm, i.e., ¹⁸O₂-labeled CO₂ (C¹⁸O₂) and nitric oxide (NO), have been introduced in an attempt to provide better estimates of membrane conductance. Heller et al. (p. 606) made single-breath measurements of the pulmonary diffusing capacity (DL) with both gases at a variety of breath-holding periods. The ratio DL_C¹⁸O2/DL_NO was lower than was theoretically predicted, probably owing to underestimation of Dm_CO2. The results are consistent with the hypothesis that Dm_NO is close to the measured value of DL_NO.

	PERFLUOROCHEMICAL "RESCUE" OF PRETERM LAMBS WITH RESPIRATORY DISTRESS

Treatment with exogenous surfactant has dramatically improved the outcomes of premature infants with respiratory distress syndrome (RDS). Wolfson et al. (p. 624) explored the possibility of further therapeutic progress by instilling a liquid perfluorochemical (perflubron) intratracheally in anesthetized preterm lambs that were severely hypoxemic from RDS even after treatment with surfactant. Perflubron improved gas exchange and compliance and reduced barotrauma in a dose-related manner. The mechanisms of action appear to include enhanced O₂ transport due to the high solubility of O₂ in perflubron and reduced local surface tension, leading to alveolar recruitment. Ultimately, of course, the importance of these physiological effects will be judged on whether perflubron can be shown to affect patient outcomes.

	THE LARYNX PARTICIPATES IN PERIODIC BREATHING IN AWAKE LAMBS

Glottic closure has been shown to occur during central apneas in awake lambs. Kianicka et al. (p. 669) have extended this work by recording laryngeal and abdominal muscle activities during periodic breathing induced by return to normoxia following hypocapnic hypoxia. Thyroarytenoid muscle activity and presumably glottic closure were present during the apneic phase of each periodic cycle, whereas phasic respiratory cricothyroid and abdominal muscle activities disappeared. The authors speculate that this pattern may preserve alveolar oxygen stores but also note that it may promote ventilatory instability.

	DELAYED LUNG DEPOSITION OF WAX-COATED PARTICLES

Pillai et al. (p. 717) measured the delayed deposition of wax-coated disodium fluorescein and pentamidine aerosols in the lungs of anesthetized dogs. Dissolution half times of coated fluorescein (~5 min) and pentamidine (~2.5 min), measured from their appearance in venous blood, were threefold greater than values for uncoated particles. Absorption half time (~40 min) of wax-coated fluorescein mixed with ^99mTc-labeled iron oxide, measured by using gamma imaging, was threefold greater than values for uncoated particles. Inhalation of these particles had no deleterious effect on pulmonary function. The delayed release of coated drug-containing aerosols may have therapeutic application.