Patterns of brain activity in response to respiratory stimulation in patients with idiopathic hyperventilation (IHV).

Dyspnoea, usually defined as an uncomfortable awareness of breathing, is one of the most frequent and distressing symptoms experienced by patients with lung disease. Idiopathic hyperventilation (IHV) has unknown aetiology and little is known about the mechanisms that cause the characteristic sustained hypocapnia and chronic dyspnoea. We have shown in IHV and other chronic respiratory disorders that air hunger is the dominant sensation during exercise, while resting breathlessness is characterised by an affective component. The increased drive to breathe in IHV, and indeed dyspnoea in all chronic respiratory disorders, might be better understood if the central mechanisms of dyspnoea were known. The aim of the present study was to characterise the cortical processing of respiratory-related sensory inputs in patients with IHV. Four patients with IHV were studied with ethical approval. Respiratory stimulation was produced using transient occlusion of inspiration (TIO) during spontaneous breathing (delivered in early inspiration with duration c. 300 ms; this is well tolerated) while BOLD fMRI was performed on a 3 Tesla Siemens Trio. TIO was associated with significant activation in sensorimotor and pre-motor cortical areas and the cerebellum, notably the anterior insula, an area previously associated with breathlessness in healthy volunteers. These preliminary observations on the pattern of brain activity in response to respiratory stimulation support the hypothesis that breathlessness in IHV may reflect inappropriate cortical processing of respiratory-related sensory inputs.

Muscle oxygenation and ATP turnover when blood flow is impaired by vascular disease.

31P magnetic resonance spectroscopy (31P MRS) and near-infrared spectroscopy (NIRS) are combined to study interactions between oxidative ATP synthesis rate, perturbation of the creatine kinase equilibrium, and cellular oxygenation state in calf muscle of normal subjects and patients with muscle perfusion impaired by peripheral vascular disease.

Mitochondrial function and oxygen supply in normal and in chronically ischemic muscle: a combined 31P magnetic resonance spectroscopy and near infrared spectroscopy study in vivo.

PURPOSE: We used (31)P magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) as a means of quantifying abnormalities in calf muscle oxygenation and adenosine triphosphate (ATP) turnover in peripheral vascular disease (PVD). METHODS: Eleven male patients with PVD (mean age, 65 years; range, 55-76 years) and nine male control subjects of similar age were observed in a case-control study in vascular outpatients. Inclusion criteria were more than 6 months' calf claudication (median, 1.5 years; range, 0.6-18 years); proven femoropopliteal or iliofemoral occlusive or stenotic disease; maximum treadmill walking distance (2 km/h, 10 degrees gradient) of 50 to 230 m (mean, 112 m); ankle-brachial pressure index of 0.8 or less during exercise (mean, 0.47; range, 0.29-0.60). Exclusion criteria included diabetes mellitus, anemia, and magnet contraindications. Simultaneous (31)P MRS and NIRS of lateral gastrocnemius was conducted during 2 to 4 minutes of voluntary 0.5 Hz isometric plantarflexion at 50% and 75% maximum voluntary contraction force (MVC), followed by 5 minutes recovery. Each subject was studied three times, and the results were combined. RESULTS: Compared with control subjects, patients with PVD showed (1) normal muscle cross-sectional area, MVC, ATP turnover, and contractile efficiency (ATP turnover per force/area); (2) larger phosphocreatine (PCr) changes during exercise (ie, increased shortfall of oxidative ATP synthesis) and slower PCr recovery (47% +/- 7% [mean +/- SEM] decrease in functional capacity for oxidative ATP synthesis, P = .001); (3) faster deoxygenation during exercise and slower postexercise reoxygenation (59% +/- 7% decrease in rate constant, P = .0009), despite reduced oxidative ATP synthesis; (4) correlation between PCr and NIRS recovery rate constants (P < .02); and (5) correlations between smaller walking distance, slower PCr recovery, and reduced MVC (P < .001). The precision of the key measurements (rate constants and contractile efficiency) was 12% to 18% interstudy and 30% to 40% intersubject. CONCLUSION: The primary lesion in oxygen supply dominates muscle metabolism. Reduced force-generation in patients who are affected more may protect muscle from metabolic stress.