HYPOXIC CHALLENGE ACTIVATES HUMAN SYMPATHETIC BRAINSTEM AND HYPOTHALAMIC SITES

Kurzfassung

BACKGROUND: Peripheral carotid chemoreceptors, which raise sympathetic activation at the brainstem level, may be altered trough atmospheric condition and is further affected by weightlessness-induced neural plasticity. However, human peripheral chemoreflex regulation in the brainstem is poorly understood due to the lack of suitable methodologies. Therefore, we combined measurements of beat-by-beat blood pressure and SpO2, and high-resolution functional magnetic resonance imaging (fMRI) to elucidate human brainstem circuits engaged through hypoxic peripheral chemoreceptor activation. METHOD AND MATERIAL: We submitted 12 healthy men (29.7 ±6.6 years; 24.0 ±1.86 kg/m2) to five hypoxic episodes by breathing 10% oxygen for 180 seconds followed by 90 seconds normoxia during multiband fMRI brain acquisitions. We monitored continuous finger arterial blood pressure using customized hardware, ECG, and SpO2. Brainstem and hypothalamus fMRI images were analyzed to identify nuclei involved in peripheral chemoreflex processing. Systolic blood pressure (SBP) and SpO2 time courses were correlated with the blood-oxygen-level-dependent signals with a general linear model. RESULTS: With hypoxia, SpO2 decreased by 12.32 ±3.68% (p < 0.01), heart rate increased 13.86 ±3.47 (p < 0.01), and SBP decreased with hypoxia 5.45 ±5.5 mmHg (p < 0.01). In the brainstem, the nucleus tractus solitarii (t-values: SpO2: 5.9; SBP: 4.79), the caudal ventrolateral medulla (SBP: 5.59), intermediate reticular nucleus (SBP: 5.98), nucleus ambiguus (SBP: 5.59), dorsal motor nucleus of the vagal nerve (SBP: 4.79), and inferior olive (SpO2: 4.7, SBP: 6.16) were identified with high sensitivity and corrected for multiple comparisons (p < 0.01). Furthermore, we observed activation of the following hypothalamic nuclei: paraventricular nucleus (SpO2: 7.67), anterior and lateral hypothalamic area (SpO2: 7.67, SBP: 4.79), supraoptic nucleus, and tuberomammillary nucleus (SpO2: 7.07). CONCLUSION: High-resolution brainstem fMRI during repeated hypoxia traces brainstem circuits engaged by peripheral chemoreceptors. This methodology allows the analysis of neural adaptation to atmospheric conditioning and short- and long term weightlessness. Furthermore, the understanding of the peripheral chemoreceptor contributions to human cardiovascular disease may enlighten not only antihypertensive therapy.