Vol. 83, Issue 5, 1411-1412, 1997

THIS MONTH IN THE JOURNAL
This Month in the Journal

DYNAMIC PROPERTIES OF LUNG PARENCHYMA

MAPPING BRAIN ACTIVITY DURING SPEECH

CENTRAL COMMAND OF HEART RATE IN EXERCISE

EXERCISE AND SUSCEPTIBILITY TO VIRAL INFECTION

INTRAVASCULAR MACROPHAGES AND ACUTE LUNG INJURY

NITRIC OXIDE AND FETAL LUNG LIQUID PRODUCTION

CATECHOLESTROGENS AND EXERCISE TRAINING

EXPIRATORY PROLONGATION BY VAGAL AFFERENTS IN THE NEONATAL RAT BRAIN STEM IN VITRO

PREGNANCY AND STRESS-INDUCED HYPERTHERMIA: INFLUENCE OF NICOTINE

WHAT LIMITS TISSUE O₂ UPTAKE?

OVARIECTOMY AND THE CONTROL OF BREATHING

DYNAMIC PROPERTIES OF LUNG PARENCHYMA

Yuan et al. (p. 1420) used a frequency response test with pseudorandom length oscillations to study the contribution of the tissue fiber network and interstitial cells to stiffness and damping behavior in strips of guinea pig lung. The results were interpreted with a linear viscoelastic model. Both tissue damping and stiffness decreased with strain amplitude and increased with mean force. After methacholine challenge, damping and stiffness increased by <15%. Interstitial cell death had no effect on the strain amplitude or mean force dependence on tissue stiffness but decreased energy dissipation by 10%, presumably because of the absence of actin-myosin cross-bridge cycling. The authors extend the findings to the intact lung, inferring that the connective tissue network may dominate parenchymal mechanics but that the tone or contraction of interstitial cells may also exert some influence. The report is discussed in an Invited Editorial by Ludwig (p. 1418).

MAPPING BRAIN ACTIVITY DURING SPEECH

Speech requires volitional control of air flow, serving communication rather than homeostasis. Murphy et al. (p. 1438) used positron emission tomography to map cortical areas in humans, activated during this motor behavior. Using a phrase designed to minimize language processing ("Buy bobby a poppy"), the authors developed a scheme to distinguish among movement, language, vocalization, and hearing. Activation in areas specifically related to control of airflow was seen bilaterally in the sensorimotor and motor cortices, the supplemental motor area, and in the thalamus and cerebellum. This bilaterality contrasts with the unilateral distribution of many sites involved with language, e.g., Broca's area.

CENTRAL COMMAND OF HEART RATE IN EXERCISE

At the onset of exercise, there is an increase in heart rate that cannot be explained by reflex activation but has been attributed to a neural "central command" that is subject to operant conditioning. Chefer and colleagues (p. 1448) examined the brain areas involved in central command in monkeys trained to attenuate the tachycardia of exercise. Different brain sites, located mostly in thalamic and limbic structures, were electrically stimulated at rest, during exercise alone, or during operantly controlled slowing of heart rate during exercise. An area was identified where stimulation increased heart rate both at rest and during exercise but where stimulation effects were attenuated during operant heart rate control. The investigators concluded that this brain area plays a significant role in the central command responsible for increased heart rate during exercise.

EXERCISE AND SUSCEPTIBILITY TO VIRAL INFECTION

Davis et al. (p. 1461) report that exercise makes mice more susceptible to respiratory infection. Mice were exercised moderately for 30 min or to exhaustion. After 15 min of rest, they were lightly anesthetized and infected intranasally with herpes simplex virus type 1 (HSV-1). Morbidity and mortality were monitored over the next 21 days. In other experiments, alveolar macrophages were obtained shortly after exercise and infected with HSV-1. The 41% mortality in strenuously exercised mice was significantly greater than in control unexercised mice (16%). Morbidity was also increased. Moderate exercise had no effect on morbidity or mortality. However, antiviral resistance of macrophages was decreased by both moderate and strenuous exercise.

INTRAVASCULAR MACROPHAGES AND ACUTE LUNG INJURY

Pulmonary intravascular macrophages are prominent in hoofed mammals. Animals with such macrophages show marked pulmonary hemodynamic changes and acute lung injury in response to intravenous infusion of gram-negative bacteria. By treating newborn lambs with liposomes containing the heavy metal chelating agent dichloromethylene diphosphonate, Sone et al. (p. 1499) destroyed >90% of pulmonary intravascular macrophages and abolished the hemodynamic responses to bacteria. Macrophage numbers and hemodynamic response both returned to close to normal after 2 wk. These studies strongly suggest that intravascular macrophages cause the lung hemodynamic changes and injury induced by infusion of gram-negative bacteria.

NITRIC OXIDE AND FETAL LUNG LIQUID PRODUCTION

The transition to air breathing at birth involves a dramatic decrease in pulmonary vascular resistance and the net resorption of fetal lung fluid. There is evidence that nitric oxide plays an important role in the former process. Cummings (p. 1538) asked whether it might also influence the reabsorbtion of lung fluid by inhibiting lung liquid secretion. He measured the net rate of lung liquid production in fetal sheep at 130 days gestation by measuring the dilution of instilled radiolabeled albumin. When saline saturated with nitric oxide was instilled, the net rate of liquid production decreased, and pulmonary blood flow increased. The results suggest that the nitric oxide production at birth, which contributes to pulmonary vasodilation, may also contribute to the net lung fluid resorption required for air breathing.

CATECHOLESTROGENS AND EXERCISE TRAINING

Catecholestrogens (CEs), a major metabolic product in estrogen metabolism, are suspected to play a role in exercise-induced menstrual irregularities. De Crée et al. (p. 1551) studied CE metabolism in nine untrained women during a control reproductive cycle and during a cycle that included two 5-day programs of training on a bicycle ergometer. The results are complex but suggest that CE production was increased after training. At the same time, resting norepinephrine (NE) levels increased. Because CEs competitively inhibit the biological decomposition of NE by catechol-O- methyltransferase, these findings suggest that NE deactivation is slowed in response to training.

EXPIRATORY PROLONGATION BY VAGAL AFFERENTS IN THE NEONATAL RAT BRAIN STEM IN VITRO

The timing of phase transitions in the respiratory cycle is importantly modulated by feedback to the brain stem respiratory controller derived from stretch receptors in the lung. Whereas such reflex modulation is known for anesthetized and decerebrate animals, the operation of such feedback in highly reduced preparations remains to be elucidated. Mellen and Feldman (p. 1607) investigated such reflexes in the brain stem of the neonatal rat in vitro using a semi-intact preparation in which the lungs were connected to the brain stem by the vagus nerve. The results reveal that lung inflation or electrical stimulation of the vagus prolonged expiration. A lung inflation held throughout expiration produced the greatest lengthening of that phase. The results reveal that the neural circuitry mediating pulmonary afferent modulation of expiratory duration is retained by this in vitro preparation.

PREGNANCY AND STRESS-INDUCED HYPERTHERMIA: INFLUENCE OF NICOTINE

During the stress of exposure to a novel environment, body temperature rises in male and nonpregnant female rats. This response is observed on day 10 of gestation in pregnant rats but not on days 15 and 20. Fewell and Tang (p. 1612) investigated the effect of chronic nicotine exposure on the hyperthermic response to a simulated open field. Nicotine increased the core temperature response in nonpregnant rats. In pregnant rats at days 20 and 21 of gestation, the hyperthermic response was restored by chronic administration of nicotine. Possible mechanisms for this action of nicotine include alterations in brown adipose tissue in addition to accentuation of plasma corticosterone and epinephrine responses to stress.

WHAT LIMITS TISSUE O₂ UPTAKE?

The physiological basis of reduced metabolic rate below a critical level of O₂ delivery (O₂) has vexed investigators for many years. Two possible explanations are reduced capillary-to-mitochondrial diffusive transport and change in convective blood flow distribution within or between tissues. Curtis et al. (p. 1687) decreased the O₂ affinity of hemoglobin in an isolated dog limb to raise capillary PO₂ and enhance diffusion. This would maintain O₂ uptake by greater extraction at lower O₂ if diffusion were key but would not change critical O₂ if blood flow redistribution were responsible. The authors found no change in critical O₂, favoring the blood flow redistribution hypothesis. However, the results are tantalizing because O₂ extraction at critical O₂ was 79% in the experimental runs and 75% in controlsa difference with marginal statistical significance. It is, therefore, possible that both diffusive and convective O₂ transport phenomena together establish critical O₂.

OVARIECTOMY AND THE CONTROL OF BREATHING

Although it is known that ovarian hormones cause hyperventilation and increased ventilatory responses to hypoxia and hypercapnia, the site of action is unknown. Tatsumi et al. (p. 1712) studied anesthetized cats before and after ovariectomy. Ovariectomy did not change resting ventilation but reduced the ventilatory and carotid sinus nerve activity responses to isocapnic hypoxia, without affecting the central (integrative) translation of carotid sinus nerve activity to ventilatory output. Thus the major action of ovarian hormones at physiological levels on hypoxic ventilatory responsiveness appears to be via the peripheral chemoreceptors.