Journal of applied physiology: respiratory, environmental and exercise physiology最新文献

A technique was developed to locate the site of slow-wave origin (pacemaker) in a sheet of smooth muscle tissue. Evoked slow waves were used to measure conduction velocities in the two dimensions of sheets of smooth muscle. These conduction velocities were used to "triangulate" to the pacemaker site by an iterative minimization process. The model was tested by triangulating to events evoked from known regions within sheets of canine gastric muscle. The technique was used to determine the sites of origin of spontaneous slow waves and the shift in the spontaneous pacemaker caused by localized injury. This technique will be useful in locating pacemaker regions and to study the factors that affect the origin and frequency of slow waves in syncytial tissues. The triangulation technique should be applicable to intact organs as well as isolated sheets of muscle.

The effects have been investigated of the regulatory peptides, substance P (SP) and bombesin, on the secretion of [14C]glucosamine-labeled trichloroacetic acid-phosphotungstic acid precipitable glycoproteins by canine tracheal explants. SP (10(10) to 10(-7) M) induced a dose-dependent increase in secretion of high-molecular-weight (greater than 2 X 10(6) radiolabeled glycoproteins predominantly from the submucosal glands. On a molar basis, SP [median effective concentration (EC50) = 8.2 X 10(-10) M] was about 1,000-fold more potent than methacholine (EC50 = 6.3 X 10(-7) M). Bombesin (10(-10) to 10(-4) M) had no effect on glycoprotein secretion. The time course of SP effect was characterized by an initial stimulation of glycoprotein secretion followed by a period of inhibition, suggesting that it rapidly exhausts a pool of glycoprotein, possibly that present within the duct lumen of the submucosal gland. Consistent with this are the findings that SP-induced secretion of glycoprotein was augmented by preincubation with methacholine while methacholine-induced secretion was diminished by preincubation with SP. Our findings show that SP is a potent stimulant of airway glycoprotein secretion in vitro and suggest that it acts by increasing the rate of clearance of mucus from the ducts of the submucosal gland, possibly by induced constriction of the secretory tubules and collecting duct. A role is discussed for SP in mucus hypersecretion induced by local axonal reflexes in the airway mucosa.

This review provides a brief summary of certain recent advances in our understanding of receptor regulation, signal transduction, and the diverse pathways by which receptor-ligand complexes are internalized and delivered to specific organelles, together with recycling of receptors back to the cell surface. Emphasis is also given to the importance of methodological advances in receptor isolation, immunologic analysis of receptor structure and function, the development of new instrumentation for microchemical characterization of very small amounts of receptor material, and the increasing use of genetic engineering techniques to isolate the genes for receptors and their regulatory subunits, to transfer such genes between cells, and to study receptor function by creating structurally modified receptors via subtle changes in gene structure.

The tremorogenic effect of high pressure was antagonized in guinea pigs by intravenous treatment with taurine in doses of 250 and 500 mg/kg. Also pretreatment with 250 mg/kg taurine suppressed tremor development as evidenced by increased threshold and decreased amplitude. It is hypothesized that antagonism of pressure-induced tremor by taurine may be related to changes in membrane calcium transport.

A technique is described on how to calculate the pulmonary resistance and compliance from the higher order harmonics present in mouth flow and transpulmonary pressure signals during spontaneous breathing. The estimates of resistance and compliance (or rather reactance) obtained from these harmonics following a conventional Fourier transform are not reliable because of a lack of reproducibility. This is obviated by a preliminary smoothing of the signals by means of auto- and cross-correlation functions. Both the conventional and the modified technique yield identical results for the fundamental component of breathing.

We require repeated blood samples from rats over long periods in our studies on obese hyperlipemic animals and normal controls. Under our conditions of lipid adnormality and exercise previously reported techniques did not give long-term cannula patency. We have thus developed a technique using thromboresistant heparin-treated Silastic tubing and a mesh-stabilized metal cannula at the base of the skull. The tubing is inserted into the vena cava without occlusion and the tip lying in the region of the termination of the hepatic veins. The tubing exists from the abdomen through the incision and runs subcutaneously to a metal tube protruding from the skin. It is closed with a short length of polyethylene tubing folded over and secured with a tight Teflon sleeve. Heparinized saline is used to fill the cannula and flush it at biweekly intervals. The cannulas remain patent for long periods with 59% permitting withdrawal of blood at 120 days. Loss of function is random after 30 days when 100% were patent. A significant number remain functional at 200 days.

Six healthy male subjects performed three exercise tests in which the power output was increased by 100 kpm/min each minute until exhaustion. The studies were carried out after oral administration of CaCO3 (control), NH4Cl (metabolic acidosis), and NaHCO3 (metabolic alkalosis). Ventilation (VE), O2 intake (VO2), and CO2 output (VCO2) were monitored continuously. Arterialized-venous blood samples were drawn at specific times and analyzed for pH, PCO2, and lactate concentration. Resting pH (mean +/- SE) was lowest in acidosis (7.29 +/- 0.01) and highest in alkalosis (7.46 +/- 0.02). A lower peak power output (kpm/min) was achieved in acidosis (1,717 +/- 95) compared with control (1,867 +/- 120) alkalosis (1,867 +/- 125). Submaximal VO2 and VCO2 were similar, but peak VO2 and VCO2 were lower in acidosis. Plasma lactate concentration was lower at rest and during exercise in acidosis. Although lactate accumulation was reduced in acidosis, increases in hydrogen ion concentration were similar in the three conditions. We conclude that acid-base changes influence the maximum power output that may be sustained in incremental dynamic exercise and modify plasma lactate appearance, but have little effect on hydrogen ion appearance in plasma.

Little is known about weight loss and changes in body composition at extreme altitude. As part of the American Medical Research Expedition to Everest in 1981 we measured body weight, body fat, limb circumferences, dietary intake, 72-h stool fats, and 5-h urine xylose excretion at various altitudes on Caucasian and Sherpa expedition members. In Caucasians, loss of body fat accounted for 70.5% of the mean 1.9-kg weight loss during the approach march at moderate altitude but for only 27.2% of the mean 4.0-kg weight loss during residence above 5,400 m. There was a significant proportionate decrease in arm and leg circumferences during residence above 5,400 m (1.5 and 2.9 cm, respectively). On the other hand, Sherpas, who arrived in Base Camp with half as much body fat as members (9.1% vs. 18.4%), maintained weight and limb circumferences during residence above 5,400 m. Fat absorption decreased 48.5% in three subjects, and xylose excretion decreased 24.3% in six of seven subjects at 6,300 m relative to sea level. It appears that muscle catabolism and malabsorption contribute significantly to weight loss at high altitude. High percent body fat does not protect against loss of muscle tissue. Sherpas do not appear susceptible to some of the changes affecting Caucasians.

Serum triglyceride (TG) levels are lower in exercise-trained (ET) compared with control rats throughout a 24-h period (P less than 0.01-0.001). To understand this phenomenon, the relationship between serum TG concentration and hepatic very low density lipoprotein (VLDL)-TG secretion rate was studied in intact rats. In addition, hepatic TG secretion was measured in isolated perfused liver and TG removal by isolated perfused hindlimbs at rest and during simulated exercise. In vivo, low TG levels are consistently associated with decreased serum insulin concentration and periodic decrease in free fatty acid (FFA) levels. At rest, with comparable FFA levels, VLDL-TG secretion was 50% lower in ET rats, proportionate to the reduction in serum TG levels. Hepatic TG secretion by perfused livers of ET and control rats was similar when studied at comparable FFA and insulin levels suggesting the fall in VLDL-TG secretion with exercise training was not the result of intrinsic change in the ability of the liver to esterify and secrete TG. Perfused muscle of ET and control rats remove TG at equal rates when perfused at rest. However, during simulated exercise, TG removal was increased only in hindlimbs from ET rats. Thus, low serum TG levels in ET rats seem to be due to a combined effect of decreased hepatic TG secretion, secondary to reduced substrate and insulin supply to the liver, and increased TG removal by muscle during exercise.

The effects of insulin and cortisol on saturated phosphatidylcholine synthesis are examined in fetal type II cell cultures and in mixed cell cultures containing type II cells and fibroblasts. In 19-day fetal rat lung type II cell cultures, 100 nM cortisol and 2 nM insulin have no significant effect. Fibroblast-pneumonocyte factor results in enhanced saturated phosphatidylcholine synthesis by fetal type II cells. The significant stimulatory effect of cortisol in mixed-cell cultures is abolished in the presence of insulin or of monoclonal antibodies to fibroblast-pneumonocyte factor. Incubation of type II cells with conditioned media from fibroblasts exposed to cortisol results in increased saturated phosphatidylcholine synthesis. This process is not stimulated when type II cells are incubated with conditioned media from fibroblasts exposed to insulin and cortisol (or to insulin alone). These observations demonstrate that insulin inhibits cortisol induction of lung maturation and suggest that this antagonism results from an inhibitory effect of insulin on the elaboration of fibroblast-pneumonocyte factor by fetal lung fibroblasts.