Ventilatory responses to isocapnic, progressive hypoxic rebreathing (HVR), in supine and sitting positions, lung ventilation and gas exchange while breathing air and during 5 min of breathing 11% O2 in N2 were studied in 12 healthy young (20–28 years), 5 old (57–73 years) male subjects, and in 7 male patients with Parkinson’s disease (PD) aged 55–67 years. The piecewise linear approximation technique was used for evaluation of the ventilatory response curves, which allowed a separate analysis of slopes during minor and severe hypoxia. It has been shown that body position affected HVR. In the range of PETO2 from 60 to 35 mm Hg, the ventilatory response in the sitting position was higher than supine: in young persons by 43%, in healthy old persons by 76%, and in the PD patients by 211%. No significant differences in HVR to minor hypoxia (PETO2 from 100 to 60 mm Hg) were found in the 3 groups. During severe hypoxia (PETO2 from 60 to 35 mm Hg) the slope of minute ventilation versus O2 was 4.6 (supine) and 2.6 (sitting) times greater in healthy old men than PD patients’ slopes. PD patients compared to old controls had 32% lower alveolar ventilation, 10% lower PETO2 and 15% elevation of PETCO2 while breathing air; similar differences were found while the patients were breathing 11% O2. The reduced alveolar ventilation under severe hypoxia in patients with PD could not be attributed to mechanical restriction of lung function. We suggest that the discrepancy in HVR under minor and severe hypoxia results from dysfunction in chemoreception associated with Parkinsonism.
Adaptation to intermittent hypoxia can enhance a hypoxic ventilatory response (HVR) in healthy humans. Naturally occurring oscillations in blood dopamine (DA) level may modulate these responses. We have measured ventilatory response to hypoxia relative to blood DA concentration and its precursor DOPA before and after a 2-week course of intermittent hypoxic training (IHT). Eighteen healthy male subjects (mean 22.8+/-2.1 years old) participated in the study. HVRs to isocapnic, progressive, hypoxic rebreathing were recorded and analyzed using piecewise linear approximation. Rebreathing lasted for 5-6 min until inspired O2 reached 8 to 7%. IHT consisted of three identical daily rebreathing sessions separated by 5-min breaks for 14 consecutive days. Before and after the 2-week course of IHT, blood was sampled from the antecubital vein to measure DA and DOPA content. The investigation associated pretraining high blood DA and DOPA values with low HVR (r = -0.66 and -0.75, respectively), elevated tidal volume (r = 0.58 and 0.37) and vital capacity (r = 0.69 and 0.58), and reduced respiratory frequency (r = -0.89 and -0.82). IHT produced no significant change in ventilatory responses to mild hypoxic challenge (Peto2 from 110 to 70-80 mm Hg; 1 mm Hg = 133.3 Pa) but elicited a 96% increase in ventilatory response to severe hypoxia (from 70-80 to 45 mm Hg). Changes in HVRs were not accompanied by statistically significant shifts in blood DA content (24% change), although a twofold increase in DOPA concentration was observed. Individual subject's changes in DA and DOPA content were not correlated with HVR changes when these two parameters were evaluated in relation to the IHT. We hypothesize that DA flowing to the carotid body through the blood may provoke DA autoreceptor-mediated inhibition of endogenous DA synthesis-release, as shown in our baseline data.
Background: Short-term exposure to high-altitude hypoxia increases hypoxic ventilatory sensitivity (HVS) in healthy humans. Dopamine (DA) is the implicated neurotransmitter in carotid body (CB) chemoreceptor response, and the microenvironmental conditions in CB tissue are comparable to blood. Continuous DA infusion affected ventilation in animals and humans. Age-related oscillations in blood DA levels may influence peripheral chemoreflexes. Objective: Hypoxic ventilatory responses (HVR) relative to blood DA concentration and its precursor, dihydroxyphenylalanine (DOPA) was measured in young and elderly men during short-term altitude adaptation. Methods: Nine elderly climbers (group 1: 61 ± 1.4 years) and 7 young healthy subjects (group 2: 23 ± 2 years) were tested at sea level on day 0, on day 3 after passive transport to 2,200 m, and on day 14 after climbing to 4,200 and 5,642 m. Results: Sea level HVR in group 1 was 47% lower than in group 2, accompanied by higher blood DOPA (300%) and DA (37%) content. Initial DA and DOPA concentrations showed a negative correlation with initial HVR but a positive correlation with age. Passive transport to middle altitude (2,200 m) increased HVS, doubling HVR slopes in groups 1 and 2 and producing increased maximum expired minute ventilation during isocapnic rebreathing (29 and 28%, respectively). Day 3 2,200-meter blood DOPA content decreased by 22% in group 1 and increased by 300% in group 2. DA increased in both groups. Conclusion: The relationship between HVR and the reciprocal DA and DOPA values seen in both groups is associated with age, producing decreased DA receptor sensitivity and enhanced DA reuptake during adaptation to high altitude.
We aimed to determine the value of the paired-pulse inhibition (PPI) in the auditory cortex in patients with Parkinson's disease (PD) and analyze its dependence on clinical characteristics of the patients. The central (Cz) auditory evoked potentials were recorded in 58 patients with PD and 22 age-matched healthy subjects. PPI of the N1/P2 component was significantly (P < .001) reduced for interstimulus intervals 500, 700, and 900 ms in patients with PD compared to control subjects. The value of PPI correlated negatively with the age of the PD patients (P < .05), age of disease onset (P < .05), body bradykinesia score (P < .01), and positively with the Mini Mental State Examination (MMSE) cognitive score (P < .01). Negative correlation between value of PPI and the age of the healthy subjects (P < .05) was also observed. Thus, results show that cortical inhibitory processes are deficient in PD patients and that the brain's ability to carry out the postexcitatory inhibition is age-dependent.
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