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1 We investigated 5-hydroxytryptamine (5-HT)-receptor mediated vasoconstriction in the main, first branch and resistance pulmonary arteries removed from control and pulmonary hypertensive rats. Contractile responses to 5-HT, 5-carboxamidotryptamine (5-CT, non-selective 5-HT, agonist), and sumatriptan (5-HTID-like receptor agonist) were studied. The effects of methiothepin (non-selective 5-HT, ±2-receptor antagonist) and ketanserin (5-HT2A receptor antagonist) and GR55562 (a novel selective 5-HTID receptor antagonist) on 5-HT-mediated responses were also studied. Basal levels of adenosine 3':5'-cycic monophosphate ([cyclic AMP]j) and guanosine 3':5'-cyclic monophosphate ([cyclic GMP]j) were determined and we assessed the degree of inherent tone in the vessels under study.2 5-HT was most potent in the resistance arteries. pEC50 values were 5.6 + 0.1, 5.3 + 0.1, 5.0 + 0.2 in the resistance arteries, pulmonary branch and main pulmonary artery, respectively (n = at least 5 from 5 animals). The sensitivity to, and maximum response of, 5-HT was increased in all the arteries removed from the chronic hypoxic (CH) rats. In CH rats the pEC50 values were 5.9 + 0.2, 6.3 +0.2, 6.4 + 0.2 and the increase in the maximum response was 35%, 51% and 41% in the resistance arteries, pulmonary branch and main pulmonary artery, respectively. Sumatriptan did not contract any vessel from the control rats whilst 5-CT did contract the resistance arteries. In the CH rats, however, they both contracted the resistance arteries (responses to sumatriptan were small) (pEC50: 5-CT; 5.4+0.2) and the pulmonary artery branches (pEC50: sumatriptan, 5.4 +0.2; 5-CT, 5.4 +0.2). 5-CT also caused a contraction in the main pulmonary artery (pECmo: 6.0+0.3). 3 Ketanserin (1 nM-l gM) caused a competitive antagonism of the 5-HT response in all vessels tested.In control rats, the estimated pKb values for ketanserin in resistance arteries, pulmonary branches and main pulmonary artery were 8.3, 7.8 and 9.2, respectively. Methiothepin (1 nM-l giM) inhibited responses to 5-HT in the first branch (estimated pKb value: 7.8) and main pulmonary artery. In CH rats, the estimated pKb values for ketanserin in resistance arteries, pulmonary branches and main pulmonary artery were 7.7, 8.3 and 9.6, respectively. Methiothepin also inhibited contractions to 5-HT in the pulmonary artery branch and main pulmonary artery with estimated pKb values of 7 and 9.5, respectively. In control animals, GR55562 had no effect on responses to 5-HT in any of the vessels tested. In the CH rats the estimated pKb values for GR55562 were 6.5, 7.8 and 7.0 in the pulmonary resistance arteries, first branch and main pulmonary artery, respectively. 6 The results suggest that the increased vasoconstrictor response to 5-HT in CH rat pulmonary arteries is due to an increase in 5-HT2A-receptor mediated contraction combined with an increase in r5-HTIB-like receptor-mediated contraction. An increase in vascular tone and decreased levels of [cyclic GMP]i in the large pulmonary arteries may contribute to...

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The aim of this article is to consider how impairments in attention may affect the performance of two tasks during balance or walking in individuals recovering from acquired brain injury (ABI). Guidelines from the experimental dual-task paradigm from cognitive psychology are reviewed. In this paper, dual-task conditions are described as the use of two tasks performed simultaneously, but not necessarily following all the experimental guidelines of the dual-task paradigm. How and why dual-task costs may emerge are discussed as well as considerations for task selection. Review of literature that describes dual-task performance problems in older adults is summarized briefly as a foundation for considering how similar conditions may affect individuals with ABI. Studies of individuals with ABI of dual-task performance in balance or walking are reviewed in detail. Examination approaches including observational measures of attention as well as clinical measures of dual-task performance during walking are reviewed. Intervention concepts and approaches are described by review of intervention designs used with older adults and individuals with ABI that describe task selection and use of instructional set for dual-task training. Two intervention strategies described in the literature for treating attention problems are contrasted: (1) an explicit focus on cognitive impairments with the expectation that function will improve as a result and (2) an implicit focus on functional tasks through errorless learning with the expectation that cognition (and attention) will improve. An illustration of the use of both of these strategies in a complementary fashion to improve attention in a patient with ABI is reviewed. Current literature is limited in clearly directing assessment and intervention to improve attention after ABI, but strategies are presented and areas for future research are identified.

Aims: To investigate factors that may contribute to performance adaptation during permanent night work. Methods: Fifteen healthy subjects participated in an adaptation and baseline night sleep, directly followed by seven simulated eight-hour night shifts (2300 to 0700 hours). At the end of each shift they were taken outside and exposed to natural light for 20 minutes. They then slept from approximately 0800 hours until they naturally awoke.Results: There was a significant increase in mean performance on a visual psychomotor vigilance task across the week. Daytime sleep quality and quantity were not negatively affected. Total sleep time (TST) for each of the daytime sleeps was reduced, resulting in an average cumulative sleep debt of 3.53 hours prior to the final night shift. TST for each of the daytime sleep periods did not significantly differ from the baseline night, nor did TST significantly vary across the week. There was a significant decrease in wake time after sleep onset and sleep onset latency across the week; sleep efficiency showed a trend towards greater efficiency across the consecutive daytime sleeps. Hours of wakefulness prior to each simulated night shift significantly varied across the week. The melatonin profile significantly shifted across the week. Conclusions: Results suggest that under optimal conditions, the sleep debt that accumulates during consecutive night shifts is relatively small and does not exacerbate decrements in night-time performance resulting from other factors. When sleep loss is minimised, adaptation of performance during consecutive night shifts can occur in conjunction with circadian adaptation.

Using wire myography, we have examined the endothelin (ET) receptor subtypes mediating vasoconstriction to ET peptides in human pulmonary resistance arteries (150–200 μm, i.d.). Cumulative concentration‐response curves to ET‐1, sarafotoxin 6c (SX6c) and ET‐3 were constructed in the presence and absence of the selective antagonists FR 139317 (ETA‐selective), BMS 182874 (ETA‐selective) and BQ‐788 (ETB‐selective). All agonists induced concentration‐dependent contractions. However, the response curves to ET‐1 were biphasic in nature. The first component demonstrated a shallow slope up to 1 nM ET‐1. Above 1 nM ET‐1 the response curve was markedly steeper. Maximum responses to ET‐3 and SX6c were the same as those to 1 nM ET‐1 and 30% of those to 0.1 μm ET‐1. The order of potency, taking 0.3 μm as a maximum concentration was SX6c > > ET‐3 > ET‐1 (pEC50 values of: 10.75 ± 0.27, 9.05 ± 0.19, 8.32 ± 0.08 respectively). Taking 1 nM ET‐1 as a maximum, the EC50 for ET‐1 was 10.08 ± 0.13 and therefore ET‐1 was equipotent to ET‐3 and SX6c over the first component of the response curve. Responses to ET‐1 up to 1 nM were resistant to the effects of the ETA receptor antagonists, FR 139317 and BMS 182874 but were inhibited by the ETB receptor antagonist, BQ‐788. Conversely, responses to ET‐1 over 1 nM were inhibited by the ETA receptor antagonists, FR 139317 and BMS 182874 but unaffected by the ETB receptor antagonist, BQ‐788. The results suggest that at concentrations up to 1 nM, responses to ET‐1 are mediated via the ETB receptor, whilst the responses to higher concentrations are mediated by ETA receptors.

1 We examined the endothelin (ET) receptors mediating contractions to ET-1, ET-3 and sarafotoxin S6c (SX6c) in rat pulmonary resistance arteries by use of peptide and non-peptide ET receptor antagonists. Changes induced by pulmonary hypertension were examined in the chronically hypoxic rat. The e ect of the mixed ET A /ET B receptor antagonist SB 209670 on endothelin-mediated contraction was also examined in human pulmonary resistance arteries. 2 In rat vessels, the order of potency for the endothelin agonists was SX6c=ET-34ET-1 (pEC 50 values in control rats: 9.12+0.10, 8.76+0.14 and 8.12+0.04, respectively). Maximum contractions induced by ET-3 and ET-1 were increased in vessels from chronically hypoxic rats. 3 The ET A receptor antagonist FR 139317 (1 mM) had no e ect on the potency of ET-1 in any vessel studied but abolished the increased response to ET-1 in the chronically hypoxic vessels. The ET A receptor antagonist BMS 182874 (1 mM) increased the potency of ET-1 in control rat vessels without e ecting potency in the pulmonary hypertensive rat vessels. 4 Bosentan (non-peptide mixed ET A /ET B receptor antagonist) increased the potency of ET-1 in control rat vessels but was without e ect in the pulmonary hypertensive rat vessels. Bosentan (1 mM) inhibited responses to SX6c in control and chronically hypoxic rat vessels with pK b values of 5.84 and 6.11, respectively. The ET B receptor antagonist BQ-788 (1 mM) did not inhibit responses to ET-1 in any vessel tested but did inhibit responses to both SX6c and ET-3 (pK b values in control and chronically hypoxic rat vessels respectively: SX6c 7.15 and 7.22; ET-3: 6.68 and 6.89). BQ-788 (1 mM) added with BMS 182874 (10 mM) did not inhibit responses to ET-1 in control vessels but caused a signi®cant inhibition of responses to ET-1 in chronically hypoxic preparations. 5 SB 209670 inhibited responses to ET-1 in both control and chronically hypoxic vessels with pK b values of 7.36 and 7.39, respectively. SB 209670 (0.1 and 1 mM) virtually abolished responses to ET-1 in the human pulmonary resistance artery. 6 In conclusion, in rat pulmonary resistance arteries, vasoconstrictions induced by ET-1, SX6c and ET-3 are mediated predominantly by activation of an ET B ± like receptor. However, lack of e ect of some antagonists on ET-1 induced vasoconstriction suggests that ET-1 stimulates an atypical ET B receptor. The increase in potency of ET-1 in the presence of some antagonists suggests the presence of an inhibitory ET A -like receptor. The in¯uence of this is reduced, or absent, in the chronically hypoxic rats. Increased responses to ET-1 are observed in the chronically hypoxic rat and may be mediated by increased activation of ET A receptors. SB 209670 is unique in its potency against responses to ET-1 in both control and chronically hypoxic rats, as well as human, isolated pulmonary resistance arteries.

This study aimed to provide a comparative index of the performance impairment associated with the fatigue levels frequently experienced in workplaces that require night work. To do this, we equated fatigue-related impairment with the impairment resulting from varying levels of alcohol intoxication. Fifteen young individuals participated in two counterbalanced conditions which required them to (1). 'work' seven consecutive 8-h night shifts, and (2). consume an alcoholic beverage at hourly intervals until their blood alcohol concentration (BAC) reached 0.10%. In each condition, performance was measured at hourly intervals using a 10-min psychomotor vigilance task (PVT). Analysis indicated that as BAC increased, performance impairment significantly increased. Similarly, response times significantly increased during the first six simulated night-shifts, and lapse frequency significantly increased during the first two shifts. Equating the two conditions indicated that the first simulated night shift was associated with the greatest degree of performance impairment. In general, the impairment at the end of this shift was greater than that observed at a BAC of 0.10%. During the second and third simulated night shifts, the performance impairment was less than on the first night, but greater than that observed at a BAC of 0.05%. For the final four nights, the performance decrements generally did not exceed those observed at a BAC of 0.05%. This suggests that during a week of consecutive night shifts, adaptation of performance occurs.