Age, target-distractor similarity, and visual search.

Younger and older adults were asked to find a single target in both feature- and conjunction- search conditions. Display size varied between 2 and 8 items, and target-distractor similarity ranged from relatively low to high levels. The accuracy data indicated that older adults had particular difficulty finding targets in high-similarity conjunction-search displays containing a large number of distractors. The reaction time (RT) analyses found larger age deficits in many of these same conditions. For both groups, predictions of conjunction search based on Treisman and Sato's additive model (Journal of Experimental Psychology: Human Perception and Performance, 1990: 16, 459-478) departed significantly from actual performance. The RT data of older observers were, in large part, predicted as a simple linear function of the young adults' data. These results are discussed with respect to age differences in selective attention, generalized slowing, and an age-related loss in search efficiency.

Assessment of ventilatory function in patients with neuromuscular disease.

In early phases of neuromuscular disease, patients are either free of respiratory symptoms or have exertional dyspnea not explained by obvious obstructive or restrictive lung disease. Physical examination may be negative because generalized muscle weakness does not correlate with the degree of respiratory muscle involvement. When the diaphragm is involved, one may detect the absence of outward excursion during inspiration or even paradoxic inward inspiratory movement of the abdomen on one side. A substantial loss of respiratory muscle strength is typically accompanied by little or no change in spirometry or arterial blood gas composition. Other characteristics are moderate loss of maximal voluntary ventilation and an increase in residual volume, yet PImax and PEmax may be as low as 50% of the predicted value. In more advanced neuromuscular disease, patients may have severe symptoms if the onset is acute or subacute; however, patients with chronic advanced generalized muscle weakness do not exercise and, therefore, may not be breathless. Many patients with advanced neuromuscular disease present with daytime somnolence as a manifestation of a sleep-related breathing disorder. Physical examination may reveal generalized muscle weakness and difficulty with speech or swallowing. Signs specific to respiratory involvement include tachypnea, use of neck inspiratory muscles and abdominal expiratory muscles, and loss of chest-abdomen synchrony. Sometimes paradoxic bilateral inward movement of the abdomen with inspiration is overt. Patients may be unable to cough effectively, have scoliosis, and lack a gag reflex. At this advanced stage, PImax and PEmax are lower than 50% of the predicted value, and the vital capacity is reduced. Maximal voluntary ventilation increases, and residual volume increases further. Patients may not yet exhibit CO2 retention during the day and may even have a low PaCO3. A sleep study may reveal significant hypopneas with severe desaturation and hypercapnia, especially during REM sleep. It is important to be aware that overt ventilatory failure can occur abruptly and that measurement of arterial blood gas composition is not a reliable indicator of this danger. Therefore, it is critically important to heed clinical phenomena, such as increasing dyspnea and tachypnea, and symptoms of sleep disturbance, such as morning headache and daytime somnolence. Physicians should make serial measurements of VC and respiratory muscle strength in patients considered to be at risk for further deterioration.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of adenosine in the depolarization of hypoxic hamster diaphragm membrane in vitro.

The resting membrane potential of in vitro hamster diaphragm muscle fibers is depolarized on exposure to hypoxia. It was hypothesized that this depolarization was mediated by adenosine. It was predicted that the treatment of well-oxygenated hamster diaphragm muscle strips in vitro with adenosine or adenosine agonists would depolarize the diaphragm fiber membrane. Furthermore, resting membrane potential of hypoxic diaphragm fibers would be repolarized by (1) the removal of adenosine by the enzyme adenosine deaminase (ADA), or (2) the addition of an adenosine antagonist, BW A1433. Adenosine (10(-4) M) depolarized the membrane by 8 +/- 1 mV (p < 0.001). The adenosine agonist cyclopentyladenosine, which has predominantly A1 receptor affinity, depolarized the membrane from -75.4 +/- 5.6 mV to -68.9 +/- 5.7 mV (p < 0.001). The A2 adenosine receptor agonist 5'-N-ethylcarboxamide adenosine did not cause a significant depolarization. The addition of ADA (2 unit/ml) to hypoxic muscle returned the resting membrane potential to that of well-oxygenated fibers, p < 0.001 versus hypoxia. BW A1433 (3 x 10(-7)) also restored the membrane potential of hypoxic muscle fibers from -72 +/- 1 mV to -79 +/- 1 mV (p < 0.001). These observations suggest that adenosine via the A1 adenosine receptor mediates the hypoxic depolarization of in vitro hamster diaphragm muscle. A direct effect of adenosine on muscle membrane has not been described previously.

The effect of theophylline on hypoxic, hypercapnic hamster diaphragm muscle in vitro.

Hypoxic, hypercapnic acidosis (HHA) decreases tension and enhances fatigue in hamster diaphragm in vitro. We hypothesized that theophylline would decrease the harmful effect of HHA. Hamster diaphragm strips were studied in Krebs solution aerated with 21% O2 and 12% CO2. The force-frequency responses and the tension and relaxation of brief, submaximal contractions were studied. Mild fatigue was produced by a series of 45 submaximal contractions, after which recovery of force was followed for 15 min. Theophylline (0.55 mM) was added at the time of exposure to HHA (early theophylline) in half the strips and at the end of the fatigue run (late theophylline) in the others. In contrast to our hypothesis, early theophylline had a limited effect on force production in unfatigued HHA diaphragm strips and resulted in lower force production in the recovery period. Late theophylline improved force in the recovery period for low-frequency contractions. Thus the effect of theophylline in the setting of HHA depended on the time it was added and was beneficial only if added after the muscle stopped contracting.

Prolonged relaxation rate of inspiratory muscles in patients with sleep apnea.

To evaluate whether inspiratory muscle function is impaired in patients with sleep apnea, we measured inspiratory muscle strength and relaxation rate before and after sleep in 13 patients. The sleep apnea group was composed of eight patients with severe obstructive sleep apnea, and the non-apnea group was composed of five patients without significant sleep apnea. We chose the time constant of relaxation (TauR) as an index of impaired inspiratory muscle contractility, and in subsets of each group, we measured the inspiratory pressure-time index as an indicator of a fatiguing breathing pattern. In patients with sleep apnea, presleep TauR was 79 +/- 22 ms (SD), longer than that of normal subjects (normal, 59 +/- 7 ms) (p less than 0.05). TauR increased by 21 +/- 16 ms during sleep (p less than 0.01). In patients without apnea, presleep TauR was 67 +/- 7 ms and it did not change after sleep. Maximal inspiratory and expiratory pressures were unchanged after sleep. We conclude that patients with sleep apnea do not develop overt inspiratory muscle failure but do have impaired contractility. We speculate that hypoxemia as well as increased work load was responsible.

Hypoxic, hypercapnic acidosis decreases tension and increases fatigue in hamster diaphragm muscle in vitro.

Hypoxia and hypercapnic acidosis have been shown to have a negative inotropic effect on diaphragmatic contractility. The effect of combined hypercapnia and hypoxia was studied in vitro using hamster diaphragm strips. A 12% CO2, 21% O2, and 67% N2 gas mixture was used to produce hypoxic, hypercapnic acidosis. Force-frequency curves were generated using twitches and maximal tetanic contractions produced by stimulating with 0.2-ms pulses at 10 to 120 Hz for 300 to 500 ms. Moderate fatigue was then induced by repeated submaximal contractions (25 Hz, 160 ms, at the rate of 1/s for 45 contractions). Muscle strips exposed to hypoxic, hypercapnic acidosis had a decreased force response at all frequencies. The decrease in force was not different from that seen with hypoxia alone but was significantly worse than with hypercapnia alone. In the combined hypercapnic, hypoxia solution, tension produced by stimulating at 25 Hz for 160 ms was decreased to 52 +/- 11% of control (p less than 0.001). For these submaximal contractions, hypercapnic acidosis had a greater negative inotropic effect than did hypoxia alone. With repeated contractions, tension declined at a faster rate than in control, hypoxia alone, or hypercapnia alone. In the combined hypoxic, hypercapnic solution, the time constant of relaxation (tau) was increased prior to the start of the fatigue run compared to the control (tau = 35 +/- 6 versus 45 +/- 5 ms; p less than 0.001), and the tau increased at a faster rate than in control. These studies suggest that hypoxic, hypercapnic acidosis has a greater detrimental effect on the muscle than either abnormality alone and makes the muscle more susceptible to fatigue.

Slowing of relaxation in the fatiguing hamster diaphragm is enhanced by theophylline.

Hamster diaphragm muscle strips were treated with theophylline (100 mg/l) or caffeine (100 mg/l) to study the effect on the time constant of relaxation (tau) during repeated contractions and with recovery. Two stimulation protocols were used: a high-tension time index (TTI, 60 Hz, 160 ms, 2/s) and a low TTI (25 Hz, 160 ms, 1/s). In the high TTI protocol an early increase in the tau was noted in theophylline but not in caffeine or control. In the low TTI protocol there was no difference in tau with theophylline. The combination of theophylline (100 mg/l) and verapamil (5 microM) was also studied. Verapamil decreased force in contractions of 300-ms duration but not in those lasting 160 ms and had no effect on tau. It did not block the prolongation of tau seen with theophylline. These studies suggest that theophylline has a direct effect on relaxation of skeletal muscle, which is not prevented by verapamil, and also that external calcium may be important for sustained contractions of skeletal muscle.

Interaction of theophylline, verapamil, and diltiazem on hamster diaphragm muscle force in vitro.

The effect of the calcium channel blocker verapamil (5 microM) or diltiazem (5 microM) on force production and resting membrane potential (Em) was studied in the hamster diaphragm muscle. The calcium channel blockers decreased force at high frequencies of stimulation and decreased Em by 3 +/- 1 mV. The interaction of theophylline and the calcium channel blockers was also studied. When given simultaneously, the calcium channel blockers prevented the increase in force at high frequencies with theophylline at 1 mM and at all frequencies with theophylline at 0.55 mM. There was no change in Em when theophylline and calcium channel blockers were given together. Similar results were obtained by removing external calcium. The decrease in force produced by verapamil was not reversed by subsequent addition of theophylline. Theophylline did reverse the decrease in force produced by diltiazem. Verapamil reversed the increase in force at high frequencies produced by theophylline. Diltiazem reversed the force increase at low frequencies as well. These studies suggest that extracellular calcium is important in skeletal muscle contractility especially at high frequencies. Extracellular calcium is also important for the potentiation of force and the hyperpolarization of the Em produced by theophylline. The mechanism by which extracellular calcium contributes to these actions of theophylline is not known.

Effect of low chloride on relaxation in hamster diaphragm muscle.

With muscle fatigue the chloride (Cl-) conductance of the sarcolemmal membrane decreases. The role of lowered Cl- conductance in the prolongation of relaxation seen with fatigue was studied in isolated hamster diaphragm strips. The muscles were studied in either a Krebs solution or a low Cl- solution in which half of the NaCl was replaced by Na-gluconate. Short tetanic contractions were produced by a 160-ms train of 0.2-ms pulses at 60 Hz from which tension (T) and the time constant of relaxation were measured. Resting membrane potential (Em) was measured using KCl-filled microelectrodes with resistances of 15-20 M omega. Mild fatigue (20% fall in tension) was induced by 24-25 tetanic contractions at the rate of 2/s. There was no difference in Em or T in the two solutions, either initially or with fatigue. The time constant of relaxation was greater in low Cl- solution, both initially (22 +/- 3 vs. 18 +/- 5 ms, mean +/- SD, P less than 0.05) and with fatigue (51 +/- 18 vs. 26 +/- 7 ms, P less than 0.005). Lowering of sarcolemmal membrane Cl- conductance appears to play a role in the slowing of relaxation of hamster diaphragm muscle seen with fatigue.

Effect of theophylline on membrane potential and contractile force in hamster diaphragm muscle in vitro.

Theophylline enhances the force of diaphragmatic contraction and delays fatigue. The mechanism is not known, but recent evidence suggests it may act at the cell membrane. To test this hypothesis, we studied the effect of theophylline on resting membrane potential and tension in hamster diaphragm cells. Muscle strips were obtained from five adult hamsters and placed in Krebs solution, aerated with 95% O2, 5% CO2. Resting membrane potential was measured using 3-M KCl-filled glass microelectrodes; 15-22 fibers in each strip were sampled. Force frequency curves (twitch to 100 Hz) were obtained. The muscle bath was then changed to one containing 100 mg/liter (0.55) theophylline. Resting membrane potential was -76 +/- 3 mV (mean +/- S.D.) in Krebs solution and increased to -85 +/- 3 mV (P less than 0.01) with added theophylline. Tension increased from 5% (at 100 Hz) to 20% (at 10 Hz) with theophylline. Hyperpolarization indicates an increase in intracellular to extracellular potassium concentration. Net potassium outflow occurs with each contraction, causing the cell membrane to become depolarized with repeated contractions, ultimately leading to fatigue. The hyperpolarization of the skeletal muscle cell membrane observed with theophylline may play an important role in prolonging time to fatigue.

Ventilatory muscle function during exercise in air and oxygen in patients with chronic air-flow limitation.

Ventilatory muscle function was examined at rest and during exercise on a cycle ergometer in 8 patients with moderate to severe chronic air-flow limitation (FEV1, 32 +/- 4% predicted) in air and in oxygen. The diaphragmatic electromyogram (EMG) was measured using an esophageal electrode. In addition, measurements of esophageal (Pes), gastric (Pga), and transdiaphragmatic (Pdi) pressures and abdominal wall movements were made. Patients exercised to exhaustion at a constant submaximal workload (80% of maximal power output) inspiring air or 40% O2 in random order on separate days. At end-exercise in air, tidal inspiratory Pes swings were 36 +/- 4% of static maximal inspiratory Pes, and inspiratory Pdi swings were 45 +/- 7% of the static maximal Pdi. Arterial oxygen saturation decreased from 91 +/- 2% at rest to 80 +/- 5% at end-exercise in air. During exercise in air, 5 patients demonstrated a persistent and greater than 20% fall in the ratio of high frequency (150 to 350 Hz) to low frequency (20 to 46 Hz) power (H/L) of the diaphragmatic EMG, indicating impending diaphragmatic fatigue, and 2 patients had paradoxical motion of the abdominal wall. Exercise time at the same constant work load increased from 3.0 +/- 0.6 min in air to 6.4 +/- 1.2 min in O2 (p less than 0.005). At the comparable time during exercise in O2 to end-exercise in air, minute ventilation was less by 13% (p less than 0.005), which was entirely attributable to a lower frequency of breathing. Mean inspiratory and expiratory flows and heart rate were all significantly lower.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the effects of ketotifen and clemastine on cutaneous and airway reactivity to histamine and allergen in atopic asthmatic subjects.

We compared the effects of ketotifen, a drug with antihistaminic and antianaphylactic properties, with those of clemastine, a conventional H1 antihistamine, on cutaneous and airway reactions to histamine and allergen in atopic asthmatic subjects. Eight subjects received ketotifen, and seven subjects received clemastine, 1 mg twice daily, for two periods of 3 wk. A 2-week interval separated the periods of medication. Maximum expiratory flow rates were measured before and after each treatment period and did not change significantly. Bronchial provocation testing to histamine was performed before and after the first period of medication, and the provocative concentration of histamine required to reduce the forced expiratory volume in 1 sec by 20% from control was increased 4.9-fold by ketotifen (p less than 0.02) and 6.5-fold by clemastine (p less than 0.01). Quantitative histamine and allergen skin testing performed before and after the second period of medication demonstrated significant attenuation of the cutaneous reactions by both medications. Neither medication, however, afforded significant protection against inhaled allergen. Our results suggest that, in the doses used, ketotifen has antihistaminic actions in man equivalent in potency to clemastine but does not appear to have significant additional effects on immediate skin or bronchial responses to allergen.

Relaxation rate of mouth pressure with sniffs at rest and with inspiratory muscle fatigue.

The relaxation rate of transdiaphragmatic pressure (Pdi) after voluntary contractions of the diaphragm slows with fatigue. We determined a range of values for the relaxation rate of mouth pressure (Pm) after voluntary contractions of the inspiratory muscles in 27 normal men and women at various lung volumes at rest. Values were similar for both sexes. The relaxation rates were similar at functional residual capacity (FRC) and below FRC, but were greater above FRC (p less than 0.05). In addition, we studied the effect of diaphragmatic fatigue induced by inspiratory resistive loading on the relaxation rates of Pdi and Pm with voluntary contractions of the inspiratory muscles in 6 subjects. With fatigue, the relaxation rates of Pdi and Pm both decreased by similar amounts, indicating that a decrease in the relaxation rate of Pm is as useful a predictor of inspiratory muscle fatigue as a decrease in the relaxation rate of Pdi has been shown to be for the diaphragm. The relaxation rate of Pm varies widely in normal subjects at rest, so isolated values do not indicate whether fatigue is present or developing. However, this may be predicted if relaxation rate decreases with serial measurements.

Ventilatory muscles during exercise in air and oxygen in normal men.

To determine whether normal ventilatory muscles fatigue during short-term high-intensity exercise, we measured diaphragmatic electromyogram (EMG, esophageal electrode), and pleural (Ppl), gastric (Pga), and transdiaphragmatic (Pdi) pressures in seven normal young men. On separate days, the subjects performed exercise to exhaustion at a constant work load (80% maximum power output) inspiring air or 40% O2. Before and after exercise, Pdimax and maximum expiratory pressure at the mouth (PEmax) were measured. At 0.5-2 min postexercise, there was a decrease in Pdimax in both air (P less than 0.02) and O2 studies (P less than 0.05). There was some recovery in Pdimax from 2-5 min postexercise in air (P less than 0.05) and complete recovery 2-5 min postexercise in O2. PEmax did not change postexercise. During exercise in air, the EMG predicted diaphragmatic fatigue in five subjects using a 20% fall of the ratio of high-frequency (150-350 Hz) to low-frequency) (20-46 Hz) power (H/L) as the criterion. Further evidence of diaphragmatic fatigue during exercise in air in two subjects was the decrease in end-inspiratory Pdi toward end exercise. There was an increase in exercise time with O2 (P less than 0.05). The improved performance in O2 was associated with a delay in the fall in H/L and the absence of the decrease in end-inspiratory Pdi in those subjects in whom such changes were observed in air.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in rate of relaxation of sniffs with diaphragmatic fatigue in humans.

The rate of relaxation of the diaphragm after stimulated (4 subjects) and voluntary (8 subjects) contractions was compared in normal young men. Stimulated contractions were induced by supramaximal unilateral phrenic nerve stimulation and voluntary contractions by short, sharp sniffs of varying tensions against an occluded airway. The rate of relaxation of the diaphragm was calculated from the rate of decline of transdiaphragmatic pressure (Pdi). In both conditions the maximum relaxation rate (MRR) was proportional to the peak transdiaphragmatic pressure (Pdi), whereas the time constant (tau) of the later exponential decline in Pdi was independent of Pdi. The mean +/- SE rate constant of relaxation (MRR/Pdi) was 0.0078 +/- 0.0002 ms-1 and the mean tau was 57 +/- 3.8 ms for stimulated contractions. The rate of relaxation after sniffs was not different, and it was not affected by either the lung volume at which occluded sniffs were performed (in the range of residual volume to functional residual capacity + 1 liter) or by the relative contribution gastric pressure made to Pdi. After diaphragmatic fatigue was induced by inspiring against a high alinear resistance there was a decrease in relaxation rate. In the 1st min postfatigue MRR/Pdi decreased (0.0063 +/- 0.0003 ms-1; P less than 0.005) and tau increased (83 +/- 5 ms; P less than 0.005). Both values returned to prefatigue levels within 5 min of the end of the studies. We conclude that the sniff may prove to be clinically useful in the detection of diaphragmatic fatigue.

Expiratory threshold load under extracorporeal circulation: effects of vagal afferents.

Nine anesthetized dogs breathed against an expiratory threshold load (ETL) applied by switching the expiratory circuit into a column of H2O to a depth of 20-30 cm. Arterial blood gas tensions were maintained in the normal range by placing the dogs under arteriovenous bypass to avoid any uncontrolled chemostimulation. There was an increase in integrated electromyogram activity of the diaphragm with the ETL. This was rarely observed after cold block of the vagus nerves which also reduced the evoked expiratory activity. The ventilatory response to hypercapnia was greatly depressed under loaded breathing whether vagal afferents were intact or blocked by cold. Both inspiratory drive and ventilatory timing were affected, suggesting that the central integration of chemosensitive afferents was altered. Proof of supraspinal projections of proprioceptive inputs from abdominal muscles was provided by the demonstration of changes in ventilatory timing during selective activation of muscle spindles in abdominal muscles by high-frequency mechanical vibration applied to the linea alba. Thus these observations suggest that during ETL breathing, a possible interaction exists between chemoreflex drive and proprioceptive afferents.

Changes in relaxation rate with diaphragmatic fatigue in humans.

Maximum relaxation rate (MRR) and the time constant of relaxation (tau) of transdiaphragmatic pressure (Pdi) was measured in four male subjects and compared with the high-to-low frequency ratio (H/L) of the diaphragmatic electromyogram (EMG) as a predictor of diaphragmatic fatigue. Pdi and inspiratory time-to-total breath duration ratios (TI/TT) were varied, and TT and tidal volume were held constant; inspiratory resistances were used to increase Pdi. Studies were performed at various tension-time indices (TTdi = Pdi/Pdimax X TI/TT). Base-line MRR/Pdi was 0.0100 +/- 0.0004 (SE) ms-1, and baseline tau was 53.2 +/- 3.2 ms. At TTdi greater than 0.20, MRR and H/L decreased and tau increased, with maximum changes at the highest TTdi. At TTdi less than 0.20, there was no change in H/L, MRR, or tau. The time course of changes in H/L correlated with those of MRR and tau under fatiguing conditions. In this experimental setting, change in relaxation rate was as useful a predictor of diaphragmatic fatigue as fall in H/L of the diaphragmatic EMG.