Effects of interval hypoxia on exercise tolerance: special focus on patients with CAD or COPD.

INTRODUCTION: Repeated short-term hypoxia (interval hypoxia) has been suggested to increase exercise tolerance by enhancing stress resistance and/or improving oxygen delivery. As low exercise tolerance contributes to mortality in patients with coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD), interval hypoxia might be a valuable preventive and therapeutic tool for these patients. Yet, mechanisms responsible for the improvement of exercise tolerance are still largely unknown. Therefore, this review intends to present an overview for better understanding of such mechanisms and to stimulate further research work on this important topic. DATA SOURCE: Articles were selected from a search of the PubMed database up to 2009 using the search terms hypoxia, intermittent, interval in various combinations with exercise, capacity, tolerance, CAD, COPD, and various haematological and cardio-respiratory parameters. RESULTS: Generally, the effects of 2-4 weeks of interval hypoxia on exercise tolerance are contrasting. Whereas aerobic exercise performance improved or remained unchanged, anaerobic performance tended even to worsen. Benefits on exercise tolerance seem to be greater in patients with CAD or COPD when compared to healthy subjects. DISCUSSION: The mechanisms responsible for these benefits are the increases in total haemoglobin mass, lung diffusion capacity, more efficient ventilation, and a decrease in the responsiveness of the adrenergic system to stimulation and/or an increase in parasympathetic activity. If confirmed in further studies, interval hypoxia might become an attractive strategy to complement the known beneficial effects of exercise training, especially in patients with CAD or COPD.

Prediction of the susceptibility to AMS in simulated altitude.

UNLABELLED: Acute mountain sickness (AMS) develops when rapidly ascending to high altitudes. However, some mountaineers will suffer from AMS even at 2,000 m and others not until 5,000 m. The awareness of the individual susceptibility for AMS would be helpful for preventive strategies. Thus, the main purpose of this paper is the comparison of existing studies dealing with the prediction of AMS susceptibility and to draw conclusions on presently most valuable tests. DATA SOURCE: A PubMed search has been performed, and preliminary observations from our laboratory have been included. The cautious conclusion derived from the reviewed 16 studies is that values of arterial oxygen saturation (SaO(2)), determined 20-30 min after exposure to simulated hypoxia equivalent to 2,300-4,200 m, seem to be the most useful predictors of AMS susceptibility (>80% correct prediction). Because the sympathetic activation during acute exposure to hypoxia may well contribute to the AMS development, parameters like heart rate variability or blood lactate could even enhance this predictability. The ventilatory response to hypoxia is easily trainable by pre-exposures to hypoxia but considers only part of the complex acclimatization process.

Neuromuscular fatigue during sustained contractions performed in short-term hypoxia.

PURPOSE: Hypoxia is known to change neuronal activity in vitro and to impair performance in vivo. The present study was designed to study neuromuscular fatigue in acute hypoxia, and we hypothesized that hypoxia results in additional fatigue during sustained contractions, presumably because of increased central fatigue. METHODS: Twelve healthy subjects participated in a normoxic (NX) and hypoxic (HX) experiment performed on separate days. Hypoxia was induced by breathing an HX air mixture containing 12% oxygen. Before, during, and after a 90-s sustained voluntary maximal contraction (MVC) of the first dorsal interosseus muscle, we measured force, voluntary activation (VA), and parameters of motor cortical excitability (motor-evoked potentials (MEP) and silent periods (SP)). Measures of peripheral nerve and muscle function, compound motor action potential (M-wave), and muscle twitch forces were also taken. RESULTS: During the MVC, force declined similarly during both HX and NX. VA decreased throughout the contraction in HX, but, surprisingly, this decrease in VA in HX did not exceed that observed in NX. Also, motor cortical excitability changed to a similar degree in HX and NX; that is, MEP amplitude and SP duration increased. M-wave amplitude decreased significantly during the sustained MVC in NX and HX. The only difference observed between NX and HX was the quicker recovery of the muscle twitch in HX, which was even potentiated after 5 min of recovery. CONCLUSION: The present results show that peripheral and central neuromuscular adaptations during a sustained fatiguing contraction are similar in NX and HX. The quicker recovery and potentiation of twitch forces in HX suggest alterations in myosin phosphorylation, which may enhance contractile force.

rTMS reveals premotor cortex dysfunction in frontal lobe epilepsy.

PURPOSE: Studies of motor cortex excitability provided evidence that focal epilepsies may alter the excitability of cortical areas distant from the epileptogenic zone. In order to explore this hypothesis we studied the functional connectivity between premotor and motor cortex in seven patients with frontal lobe epilepsy and seizure onset zone outside the premotor or motor cortex. METHODS: Low-frequency subthreshold repetitive transcranial magnetic stimulation was applied to the premotor cortex and its impact on motor cortex excitability was measured by the amplitude of motor-evoked potentials in response to direct suprathreshold stimulation of the motor cortex. RESULTS: Stimulation of the premotor cortex of the non-epileptogenic hemisphere resulted in a progressive and significant inhibition of the motor cortex as evidenced by a reduction of motor evoked potential amplitude. On the other hand, stimulation of the premotor cortex of the epileptogenic hemisphere failed to inhibit the motor cortex. The reduced inhibition of the motor cortex by remote areas was additionally supported by the significantly shorter cortical silent periods obtained after stimulation of the motor cortex of the epileptogenic hemisphere. CONCLUSION: These results show that the functional connectivity between premotor and motor cortex or motor cortex interneuronal excitability is impaired in the epileptogenic hemisphere in frontal lobe epilepsy while it is normal in the nonepileptogenic hemisphere.

Abnormal responses to repetitive transcranial magnetic stimulation in multiple system atrophy.

We studied the response of the motor cortex to brief trains of suprathreshold repetitive transcranial magnetic stimulations (rTMS) in patients with the Parkinson-variant of multiple system atrophy (MSA-P) and compared it to patients with idiopathic Parkinson's disease (PD) and healthy controls. Eight subjects were studied in each group, and patients were matched for disease severity as assessed by Hoehn & Yahr stages. rTMS was delivered at rest and during low-level contractions in trains of 10 stimulations at 5 Hz, and stimulation intensity was set to result in an motor evoked potential (MEP) in the first dorsal interosseus muscle of 0.5 to 1.0 mV. In MSA-P, MEP amplitude at rest was already reduced after the second stimulus and remained so, while it did not change in PD and controls. During contraction, MEP size did not change during the train in any group. The silent period that followed the last stimulus was of similar duration as the first stimulus in MSA-P, but was increased in PD and controls. These findings indicate that abnormal inhibition occurs within the motor cortex in MSA-P, despite dopaminergic treatment and indicate differences in cortical dysfunction between MSA-P and PD. We suggest that these abnormalities reflect the motor cortex pathology found in MSA-P.

The effects of short-term hypoxia on motor cortex excitability and neuromuscular activation.

The effects of acute hypoxia on motor cortex excitability, force production, and voluntary activation were studied using single- and double-pulse transcranial magnetic stimulation techniques in 14 healthy male subjects. Electrical supramaximal stimulations of the right ulnar nerve were performed, and transcranial magnetic stimulations were delivered to the first dorsal interosseus motor cortex area during short-term hypoxic (HX) and normoxic (NX) condition. M waves, voluntary activation, F waves, resting motor threshold (rMT), recruitment curves (100-140% of rMT), and short-interval intracortical inhibition and intracortical facilitation were measured. Moreover, motor-evoked potentials (MEPs) and cortical silent periods were determined during brief isometric maximum right index finger abductions. Hypoxia was induced by breathing a fraction of inspired oxygen of 12% via a face mask. M waves, voluntary activation, and F waves did not differ between NX and HX. The rMT was significantly lower in HX (55.79 +/- 9.40%) than in NX (57.50 +/- 10.48%) (P < 0.01), whereas MEP recruitment curve, short-interval intracortical inhibition, intracortical facilitation, maximum right index finger abduction, and MEPs were unaffected by HX. In contrast, the cortical silent periods in HX (158.21 +/- 33.96 ms) was significantly shortened compared with NX (169.42 +/- 39.69 ms) (P < 0.05). These data demonstrate that acute hypoxia results in increased cortical excitability and suggest that acute hypoxia alters motor cortical ion-channel function and GABAergic transmission.