CHEST WALL VIBRATION AND BREATHLESSNESS

Vibratory simulation of the chest wall reduces breathlessness if it is applied during inspiration but not during expiration. The study by Edo et al. (p. 1487) examines the effect of inspiratory chest wall vibration on the sensation of breathlessness and the ventilatory response to combined hypercapnia and inspiratory loading. The investigators measured ventilation, an index of inspiratory motor output, and breathlessness on a visual analog scale. Comparison of these variables with and without vibration showed that in-phase vibration decreased breathlessness elicited by inspiratory loading and hypercapnia without changing motor output. The paper is discussed in an Invited Editorial by Manning (p. 1485).

	STEROIDS AND THE DIAPHRAGM

Glucocorticoid treatment can cause diaphragm muscle dysfunction, due in part to a selective atrophy of type IIx and IIb fibers. Van Balkom and colleagues (p. 1492) evaluated whether anabolic steroid nandrolone decanoate treatment in male rats could reverse the loss of diaphragm force and muscle fiber atrophy induced by prolonged administration of methylpredisolone (MP). After 9 mo of MP administration, diaphragm muscle force was reduced by ~10%, and there was generalized atrophy of diaphragm muscle fibers. These mechanical and morphometric changes induced by MP were reversed by 3 mo of nandrolone decanoate treatment. These observations in rats may have clinical importance in humans.

	DISTRIBUTION OF PULMONARY PERFUSION DURING PARTIAL LIQUID VENTILATION

Partial liquid ventilation (PLV) is a method used to improve pulmonary gas exchange, with particular application in surfactant-deficient neonatal lungs. It involves intrapulmonary instillation of a near-functional residual capacity volume of perfluorocarbon liquid, followed by tidal ventilation with an appropriate gas mixture, rather than pumping the liquid in and out of the lungs. To evaluate the mechanisms contributing to the improved gas exchange, Doctor et al. (p. 1540) measured the effects of PLV on the distribution of pulmonary blood flow in lambs by using radiolabeled microspheres. They found that PLV resulted in a redistribution of pulmonary blood toward the nondependent lung, presumably away from the bulk of the high-density perfluorocarbon. The redistribution occurred without significant changes in total pulmonary blood flow or perfusion pressure.

	EFFECTS OF NICOTINE ON MACROMOLECULAR TRANSPORT

Mayhan and Sharpe (p. 1589) exposed the microvasculature of the hamster cheek pouch in vivo by surgical removal of the connective tissue. The pouch was then mounted in a chamber to permit its superfusion with physiological saline. Fluorescent dextran was injected intravenously, and microvascular permeability was determined from the appearance of fluorescence in the superfusate and from the numbers of extravasation sites. Nicotine inhibited the histamine-induced increase in permeability by 65-100%, an effect that was prevented by pretreatment with superoxide dismutase. It was concluded that nicotine produced free radicals, which blocked the histamine-induced increase in microvascular permeability, presumably by inactivating nitric oxide.

	NITRIC OXIDE AND HEART RATE

Does nitric oxide (NO) play a role in the vagally mediated heart rate recovery from simulated exercise? Sears et al. (p. 1596), using isolated guinea pig atria, tested the hypothesis that NO is involved in the cholinergic antagonism of the positive chronotropic response to norepinephrine. In preparations previously stimulated by norepinephrine, inhibition of NO synthesis slowed the time course of the reduction in heart rate evoked by both acetylcholine and vagal nerve stimulation. NO synthesis inhibition, however, had no effect on the magnitude of the decrease in rate evoked by either acetylcholine or vagal stimulation. The authors conclude that NO plays a functional role in the control of heart rate.

	ENDOTOXIN-INDUCED LUNG DYSFUNCTION DOES NOT DEPEND ON PLATELET-ACTIVATING FACTOR

Many studies indicate that platelet-activating factor (PAF) contributes to endotoxin-induced lung dysfunction. However, several studies have been compromised by the inadequacy of the PAF antagonists used. Snapper et al. (p. 1610) describe results with ABT-299, a new antagonist with improved specificity and potency. In sheep, the pulmonary hypertension and fall in dynamic compliance produced by intravenous PAF were completely blocked by ABT-299. However, this agent had no effect on the pulmonary hypertension, reduced dynamic compliance, leukopenia, and hypoxemia induced by endotoxin. The authors conclude that PAF does not play an essential role in the sheep's response to endotoxin.

	SUBSETS OF CIRCULATING LYMPHOCYTES IN HEATSTROKE

Circulating lymphocytes are known to be altered in heatstroke. Hammami et al. (p. 1615) examined the specificity of these alterations by determining lymphocyte subsets by immunofluorescence flow cytometry in patients with heatstroke, in heat-stressed patients who did not meet clinical criteria for heatstroke, and in normal control subjects. In heatstroke, absolute and relative numbers of six subsets of lymphocytes were reduced, and those of five other subsets were increased compared with controls. Milder, but directionally similar, changes were found in heat stress, suggesting that the two syndromes represent a continuum in this respect.

	SUCROSE INGESTION REDUCES LIPID MOBILIZATION DURING EXERCISE

Can lipid mobilization from adipose tissue during prolonged exercise be reduced by increasing the availability of carbohydrates? De Glisezinski et al. (p. 1627) estimated lipid mobilization by measuring glycerol in fluid obtained by subcutaneous abdominal adipose tissue microdialysis. Subjects exercised for 100 min at 50% of their maximum aerobic capacity. After the first 50 min of exercise, they drank 500 ml of water or a sucrose solution. Without sucrose, exercise increased plasma and dialysate glycerol, but when sucrose was given, dialysate glycerol fell. Thus sucrose ingestion reduces exercise-induced lipid mobilization.

	BRAIN NATRIURETIC PEPTIDE PROTECTS AGAINST HYPOXIC PULMONARY HYPERTENSION

Brain and atrial natriuretic peptides (BNP and ANP, respectively) can dilate pulmonary vessels and decrease the acute pulmonary vasoconstrictor response to hypoxia. Klinger et al. (p. 1646) examined the effects of chronic infusion of these pulmonary vasodilator peptides on the pulmonary arterial and right ventricular remodeling that occurs in rats exposed to 2 wk of hypobaric hypoxia (0.5 atmosphere). When the infusion rate of BNP during hypoxia was sufficient to raise BNP plasma levels above their usual hypoxic values, the right ventricular hypertrophy and pulmonary arterial remodeling usually associated with chronic hypoxia were diminished. Infusion of ANP did not have this effect. The observations suggest that BNP may be an important regulator of pulmonary vascular responses to sustained hypoxia.

	REGULATION OF GLUCOSE TRANSPORTERS IN DENERVATED MUSCLE

Muscle denervation is known to reduce glucose transporter GLUT-4 expression and to increase GLUT-1 expression. Jones et al. (p. 1661) used four lines of transgenic mice containing sequential truncations (2,400, 1,639, 1,154, and 730 bp) of the human GLUT-4 promoter linked to the chloramphenicol acyl transferase gene in studies designed to determine whether muscle denervation affected GLUT-4 and GLUT-1 gene transcription. The results of this study strongly suggest that muscle denervation results in a reduction of GLUT-4 and an increase in GLUT-1 transcription. Additionally, this study provides evidence that the DNA regulatory element responsive to muscle denervation in the mouse is located within 730 bp of the 5'-flanking promoter region of the human GLUT-4 gene.

	GAS EXCHANGE DURING PROLONGED SUBMAXIMAL EXERCISE IN HORSES

During short-term maximal exercise, the Thoroughbred horse experiences serious failure of pulmonary gas exchange. CO₂ retention and arterial hypoxemia are common, along with an excessive alveo-lar-arterial PO₂ gradient [(A-a)PO₂], which cannot be attributed to ventilation-perfusion maldistribution. The study by Hopkins et al. (p. 1723) shows that the horse fares much better during prolonged moderate-intensity exercise. Arterial PO₂ is maintained near resting levels, alveolar ventilation increases throughout, and ventilation-perfusion maldistribution and diffusion limitation contribute little or nothing to the maintained and relatively small (A-a)PO₂.