Autonomic and Cognitive Function Response to Normobaric Hyperoxia Exposure in Healthy Subjects. Preliminary Study.

Background and objective: This is the first study to investigate the effect of high-flow oxygen therapy, using a normobaric chamber on cognitive, biochemical (oxidative stress parameters and the level of neurotrophins), cardiovascular and autonomic functioning. Materials and methods: 17 healthy volunteers, eight males and nine females, with a mean age of 37.5 years, were examined. The experimental study involved ten two-hour exposures in a normobaric chamber with a total pressure of 1500 hPa, in air adjusted to 37% oxygen, 1.079% carbon dioxide and 0.44% hydrogen. Cognitive function was assessed by using Trail Making Test parts A, B and difference in results of these tests (TMT A, TMT B and TMT B-A); California Verbal Learning Test (CVLT); Digit symbol substitution test (DSST); and Digit Span (DS). Fatigue (Fatigue Severity Scale (FSS)), cardiovascular, autonomic and baroreceptor functioning (Task Force Monitor) and biochemical parameters were measured before and after intervention. Results: After 10 sessions in the normobaric chamber, significant decreases in weight, caused mainly by body fat % decrease (24.86 vs. 23.93%, p = 0.04 were observed. TMT part A and B results improved (p = 0.0007 and p = 0.001, respectively). In contrast, there was no statistically significant influence on TMT B-A. Moreover, decrease in the number of symbols left after a one-minute test in DSST was noted (p = 0.0001). The mean number of words correctly recalled in the CVLT Long Delay Free Recall test improved (p = 0.002), and a reduction in fatigue was observed (p = 0.001). Biochemical tests showed a reduction in levels of malondialdehyde (p < 0.001), with increased levels of Cu Zn superoxide dismutase (p < 0.001), Neurotrophin 4 (p = 0.0001) and brain-derived neurotrophic factor (p = 0.001). A significant increase in nitric oxide synthase 2 (Z = 2.29, p = 0.02) and Club cell secretory protein (p = 0.015) was also noted. Baroreceptor function was significantly improved after normobaric exposures (p = 0.003). Significant effect of normobaric exposures and BDNF in CVLT Long Delay Free Recall was noted. Conclusions: This study demonstrates that 10 exposures in a normobaric chamber have a positive impact on visual information and set-shifting processing speed and increase auditory-verbal short-term memory, neurotrophic levels and baroreceptor function. A response of the respiratory tract to oxidative stress was also noted. There is a need to rigorously examine the safety of normobaric therapy. Further studies should be carried out with physician examination, both pre and post treatment.

Involvement of Cardiorespiratory Capacity on the Acute Effects of Caffeine on Autonomic Recovery.

Background and objectives: As a result of ergogenic properties, caffeine has been increasingly taken prior to physical exercise, yet its effects on post-exercise recovery, considering the differences in the cardiorespiratory capacity of the individuals, has not yet been studied or fully elucidated. Optimizing the post-exercise recovery can convey advantages to physical activity practitioners. We evaluated the acute effects of caffeine on heart rate (HR) autonomic control recovery following moderate aerobic exercise in males with different cardiorespiratory capacities. Materials and Methods: We split young adult men into two groups based on their various oxygen consumption peaks (VO2 peak): (1) Higher VO2 (HO): Sixteen volunteers, peak VO2 > 42.46 mL/kg/min and (2) Low VO2 (LO): Sixteen individuals, VO2 < 42.46 mL/kg/min). The volunteers were submitted to placebo and caffeine protocols, which entailed 300 mg of caffeine or placebo (starch) in capsules, followed by 15 min of rest, 30 min of moderate exercise on a treadmill at 60% of the VO2 peak, followed by 60 min of supine recovery. Heart rate variability (HRV) indexes in the time and frequency domains were examined. Results: Effect of time for RMSSD (square root of the average of the square of the differences between normal adjacent RR intervals) and SDNN (standard deviation of all normal RR intervals recorded in a time interval) was achieved (p < 0.001). Significant adjustments were observed (rest versus recovery) at the 0 to 5th min of recovery from exercise for the LO during the placebo protocol and at the 5th at 10th min of recovery for the caffeine protocol. For the HO in both procedures we found significant alterations only at the 0 to 5th min of recovery. Conclusion: Caffeine delayed parasympathetic recovery from exercise in individuals with lower cardiorespiratory capacity.

Firefighters' basal cardiac autonomic function and its associations with cardiorespiratory fitness.

BACKGROUND: Firefighters' activities require constant adjustments of the cardiovascular system with cardiac autonomic function (CAF) playing an important role. Despite the crucial role of CAF in regulating stress response, little is known about firefighters' CAF. OBJECTIVE: We aimed to characterize the resting on-duty and off-duty CAF of male firefighters, in association with cardiorespiratory fitness (CRF). METHODS: We evaluated 38 firefighters in an on-duty rest condition and 26 firefighters in an off-duty laboratory-controlled condition. CAF was addressed by means of heart rate variability (HRV). We compared HRV measurements between CRF categories (<12METs vs ≥12METs). Wilcoxon, Mann-Whitney texts and Spearman correlation were used and General Linear Model was applied for age and BMI adjustments. RESULTS: Firefighters' resting CAF is characterized by a predominant sympathetic modulation and a large inter-individual dispersion in all HRV indices, in both groups. We found a positive correlation between a higher CRF, the overall CAF and the higher parasympathetic activity (p <  0,03). Firefighters with CRF ≥12 METs showed a higher parasympathetic modulation. CONCLUSIONS: Firefighters' resting CAF is characterized by a predominant sympathetic modulation and a large inter-individual dispersion in all HRV indices, in both groups. Our results support mandatory physical training focused in improving firefighters' CAF as a cardiopretective effect.

The cardiopulmonary effects of ambient air pollution and mechanistic pathways: a comparative hierarchical pathway analysis.

Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001) and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005). These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours) and the hemostasis pathway responds gradually over a 2-3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system.

Effect of losartan, an angiotensin II type 1 receptor antagonist on cardiac autonomic functions of rats during acute and chronic inhibition of nitric oxide synthesis.

We studied the effect of losartan on baroreflex sensitivity (BRS) and heart rate variability (HRV) of adult Wistar rats during acute and chronic inhibition of nitric oxide synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME). Chronic L-NAME administration (50 mg/kg per day for 7 days, orally through gavage) increased mean arterial pressure (MAP), heart rate but significantly decreased BRS. In addition, a significant fall of standard deviation of normal RR intervals, total spectral power, high frequency spectral power and a rise of low frequency to high frequency (LF: HF) ratio was seen. Acute L-NAME administration (30 mg/kg, i.v. bolus dose) also raised MAP and impaired HRV but it was associated with augmented BRS for bradycardia reflex. Losartan treatment (10 mg/kg, i.v.) in both acute and chronic L-NAME treated rats, decreased MAP but the difference was not significant. On the other hand, losartan administration normalized depressed BRS for bradycardia reflex and significantly reduced LF to HF ratio in chronic L-NAME treated rats. But this improvement was not observed in acute L-NAME group. These results indicate importance of mechanisms other than renin-angiotensin system in the pressor response of both acute as well as chronic L-NAME. However, autonomic dysregulation especially following chronic L-NAME appears to be partly angiotensin dependent.

A catecholamine transporter from the human parasite Schistosoma mansoni with low affinity for psychostimulants.

The trematode Schistosoma mansoni is the primary cause of schistosomiasis, a devastating neglected tropical disease that affects 200 million individuals. Identifying novel therapeutic targets for the treatment of schistosomiasis is therefore of great public interest. The catecholamines norepinephrine (NE) and dopamine (DA) are essential for the survival of the parasite as they cause muscular relaxation and a lengthening in the parasite and thereby control movement. Here we characterize a novel dopamine/norepinephrine transporter (SmDAT) gene transcript, from S. mansoni. The SmDAT is expressed in the adult form and in the sporocyst form (infected snails) of the parasite, and also in the egg and miracidium stage. It is absent in the cercariae stage but curiously a transcript missing the exon encoding transmembrane domain 8 was identified in this stage. Heterologous expression of the cDNA in mammalian cells resulted in saturable, dopamine transport activity with an apparent affinity for dopamine comparable to that of the human dopamine transporter. Efflux experiments reveal notably higher substrate selectivity compared with its mammalian counterparts as amphetamine is a much less potent efflux elicitor against SmDAT compared to the human DAT. Pharmacological characterization of the SmDAT revealed that most human DAT inhibitors including psychostimulants such as cocaine were significantly less potent in inhibiting SmDAT. Like DATs from other simpler organisms the pharmacology for SmDAT was more similar to the human norepinephrine transporter. We were not able to identify other dopamine transporting carriers within the completed parasite genome and we hypothesize that the SmDAT is the only catecholamine transporter in the parasite and could be responsible for not only clearing DA but also NE.

Pharmacologic basis for developing rational drug regimens for elderly patients.

Changes in responsiveness with age have been observed for autonomic drugs (agonists as well as antagonists, analgesics, anticonvulsants, bronchodilators, hypoglycemics, corticosteroids, and virtually every other group of drugs). As indicated earlier, however, this review is not meant to present an exhaustive treatment of the area, but rather to focus attention on the factors that contribute to alterations in sensitivity. As a secondary aim, the review serves to focus attention on the problem of adverse drug reactions, particularly those related to the practice of polypharmacy, which compounds the problem through drug interactions. As indicated in the introduction, adverse drug reactions (undesired or unwanted effects of drugs) occur more frequently in the older patient than in the young one. In the elderly, this relates to increased use of drugs, polypharmacy, diminution in the function of organs which play a role in drug distribution and elimination, and poor patient compliance. Drugs which most often result in adverse reactions in the elderly have been listed by Lamy (Table 1). It is of significance that this list includes many drugs that are obtainable over the counter without prescription, such as aspirin and antacids. Because of the widespread practice of polypharmacy in the elderly, there is an increased potential for drug interactions. Examples of drugs and the mechanisms whereby interactions occur, which are of particular significance in geriatric therapeutics, are provided in Table 3. Since monographs summarizing drug interactions have been available for a number of years, it is somewhat surprising that the magnitude of the problem is still so great. It appears clear that the more we understand about the basic changes that occur in the physiology, biochemistry, and structure of an organism as it ages, and the more we learn about basic pharmacologic principles, the better we can combine the knowledge toward the development of rational therapeutic drug regimens for the geriatric patient. For more detailed discussion, the reader is referred to Caird et al., Kayne, Vestal, Lamy, and Poe and Holloway. A summary of the major principles in prescribing drugs for the elderly, quoted from Riley, is provided in Table 2.

A role for alpha-adrenergic receptors in abnormal insulin secretion in diabetes mellitus.

To determine whether endogenous alpha-adrenergic activity contributes to abnormal insulin secretion in nonketotic, hyperglycemic, diabetic patients, alpha-adrenergic blockade was produced in normal and diabetic subjects. The diabetics had a significantly (P less than 0.01) greater increase in circulating insulin 1 h after an intravenous phentolamine infusion than did the normal subjects. During the phentolamine infusion, there was also a significant augmentation of acute insulin responses to intravenous glucose (20 g) pulses in normal subjects (P less than 0.05) and diabetics (P less than 0.02); this augmentation was fivefold greater in the diabetics. Simultaneous treatment with the beta-adrenergic blocking agent, propranolol, did not alter these findings. Thus a role for exaggerated endogenous alpha-adrenergic activity in abnormal insulin secretion of the diabetic subjects is suggested. To determine whether this alpha-adrenergic activity might be related to elevated circulating catecholamines, total plasma-catecholamine levels were compared in normal and nonketotic diabetic subjects given intravenous glucose pulses. These levels were significantly greater (P less than 0.02) in the diabetic compared to the normal group before the glucose pulse, and increased significantly in both groups (P less than 0.02 and less than 0.001, respectively) after the pulse. These data suggest that excessive catecholamine secretion may lead to an abnormal degree of endogenous alpha-adrenergic activity, which contributes to defective insulin secretion in diabetic subjects.