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[2] Elghozi, J. L., Girard, A., Fritsch, P., Laude, D., Petitprez, J. L., 2008. Tuba players reproduce a Valsalva maneuver while playing high notes. Clin. Auton. Res. 18, 96–104.

doi:10.1016/j.autneu.2009.05.063

S12.4 Right middle cerebral artery stroke dampens cardiovascular responses to music, left middle cerebral artery stroke decreases blood pressure response to pleasant music M.J. Hilz (Department of Neurology, University of Erlangen-Nuremberg, Erlangen, 91054, Germany; Departments of Neurology, Medicine, Psychiatry, New York University School of Medicine, New York, NY, 10016, USA), J. Nath (Department of Neurology, University of ErlangenNuremberg, Erlangen, 91054, Germany), S. Wong (Department of Rehabilitation Medicine, New York University School of Medicine, New York, NY, 10016, USA), S. Buechner (Departments of Neurology, Medicine, Psychiatry, New York University School of Medicine, New York, NY, 10016, USA), B. Stemper (Department of Neurology, University of Erlangen-Nuremberg, Erlangen, 91054, Germany), M.H.M. Lee (Department of Rehabilitation Medicine, New York University School of Medicine, New York, NY, 10016, USA), L. Habib-Romstöck (Department of Neurology, University of Erlangen-Nuremberg, Erlangen, 91054, Germany), P. Stadler (Department of Neurology, University of ErlangenNuremberg, Erlangen, 91054, Germany), T. Gryc (Department of Neurology, University of Erlangen-Nuremberg, Erlangen, 91054, Germany) After ischemic stroke, there may be hemisphere-specific dysfunction of autonomic modulation. Processing of music is also hemisphere-specific and valence-dependent [1]. We hypothesize that patients who experienced a stroke in the middle cerebral artery territory have hemisphere- and valence-dependent changes in autonomic responses to music. The aim of the study was, to determine cardiovascular responses to pleasant or unpleasant music in patients after left (MCA-LS) and right middle cerebral artery stroke (MCA-RS). In 17 MCA-LS (62 ± 10 years), 14 MCA-RS patients (61 ± 8 years), and 21 age-matched controls (64 ± 8 years), we monitored electrocardiographic RR-intervals (RRI), blood pressure (BP), respiratory frequency and end-tidal CO2 before and during listening to six 180 s excerpts of classical music intended to induce pleasant or unpleasant emotions (three excerpts each). After each excerpt, participants rated the perceived pleasant and unpleasant emotions on five-point Likert scales. We compared 120 s bio-signal epochs before and after onset of each excerpt, using analysis of variance for repeated measures and t-test post-hoc analysis. Significance was assumed for p < 0.05. Likert scores were higher on “pleasant” than “unpleasant” scales with “pleasant” music (and vice versa with unpleasant music) confirming that “pleasant” respectively “unpleasant” music induced the intended emotions. Music did not influence respiratory frequency and end-tidal CO2 in patients or controls. In controls and MCA-LS patients, “pleasant” and “unpleasant” music significantly decreased RRIs, i.e., accelerated heart rate (controls: pleasant music: 1001.8 ± 125.6 vs. 982.7 ± 121.4 ms, unpleasant music: 998.9 ± 124.9 vs. 980.9 ± 121.2 ms; MCA-LS: pleasant music: 935.8 ± 112.0 vs. 923.8 ± 107.1 ms, unpleasant music: 931.5 ± 110.0 vs. 908.3 ± 104.9 ms). BP increased significantly in healthy participants during “pleasant” (134 ± 18 mm Hg vs. 137 ± 18 mm Hg) music only. In MCA-LS patients BP increased slightly (139 ± 22 vs. 141 ± 25 mm Hg; p < 0.05) with unpleasant music only. In MCA-RS patients, music did not change RRI or BP. To conclude, the absent RRI and BP responses to music in MCA-RS patients but preserved responses in MCA-LS patients suggest that

autonomic processing of music largely depends on adequate function within the right MCA territory. Altered BP responses in MCA-LS patients with BP increase only to unpleasant music suggest lateralized processing of emotional valence with predominantly left-hemispheric modulation of pleasant emotions. [1] Altenmüller, E., Schürmann, K., Lim, V.K., Parlitz, D., 2002. Hits to the left, flops to the right: different emotions during listening to music are reflected in cortical lateralisation patterns. Neuropsychologia. 40, 2242–2256. Acknowledgement: The study was partially funded by the International Brain Research Foundation Inc., IBRF, Edison, NJ, USA.

doi:10.1016/j.autneu.2009.05.064

S13. Chemo-baroreflex interactions in physiological and pathological conditions S13.1 Baroreflex modulation during sleep and obstructive sleep apnea syndrome (OSAS) P. Cortelli (Dipartimento di Scienze Neurologiche, Alma Mater Studiorum, Università di Bologna, Via Ugo Foscolo, 7, 40123 Bologna, Italy) The regulatory control of the cardiovascular system including the arterial baroreceptor reflex is sleep–wake state dependent with a reduced mean value and variability of arterial blood pressure (ABP) during non-rapid eye movement sleep and a further decrease or increase in mean ABP with phasic hypertensive events, during rapid eye movement sleep. Regulation of ABP depends on feed-forward or “central command” mechanisms that evoke cardiovascular changes that are part of generalized adaptive physiologic responses and feedback or reflex mechanisms that allow a moment-to-moment control of ABP in response to inputs from peripheral receptors. Sympathetic and parasympathetic systems contribute to cardiovascular regulation and a complex network of brain stem units subserve cardiovascular autonomic control. Bilateral direct and indirect connections exist between this network and cortical areas. OSAS is characterised by repetitive apnoea/hypopnoea during sleep associated with oxygen desaturations and sleep disruption. In addition to causing abnormalities in sleep architecture and excessive daytime sleepiness (EDS) OSAS is associated with chronic abnormalities of cardiovascular autonomic regulation during sleep and wakefulness. The apneic phase of OSA is marked by frustrated respiratory efforts of increasing magnitude that elicit a strong sympathetic response because of the effects of central respiratorysympathetic coupling, the synergistic effects of hypoxia and hypercapnia, the concomitant lack of sympatho-inhibition from the normal lung inflation reflexes and the effects of baroreflexes. Sympathetic overactivity in OSAS was suggested as the possible link between OSAS and cardiovascular complications and numerous studies demonstrated that sympathetic activity during OSA is responsible for the surges in HR and ABP that occur after apnea termination. These repetitive surges in ABP not only oppose the fall that accompanies normal sleep but also represent an intense physiological stressor of baroreflex mechanisms that may contribute to the development of arterial hypertension and to increased mortality. Patients with severe OSAS show depressed baroreflex sensitivity (BRS) during daytime and sleep, and recently we demonstrated that EDS is associated with a lower BRS probably reflecting a maladaptive baroreflex bottom-up modulation of the arousal system [1].This finding could explain the role of EDS in determining the risk of hypertension in patients with sleep-related breathing disorders [2]. In OSAS the repetitive nocturnal stimulation of the baroreflex visceral afferents may change the NTS activity and its top-down and

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bottom-up modulations of ANS activity leading to chronic peripheral sympathetic overactivation that can explain hypertension and its complications and to a malfunctioning of the arousal system that can explain EDS. [1] Lombardi, C., Parati, G., Cortelli, P., Provini, F., Vetrugno, R., Plazzi, G., Vignatelli, L., Di Rienzo, M., Lugaresi, E., Mancia, G., Montagna, P., Castiglioni, P. 2008. Daytime sleepiness and neural cardiac modulation in sleep-related breathing disorders. J Sleep Res.17, 263–70. [2] Kapur, V.K., Resnick, H.E., Gottlieb, D.J., Sleep Heart Health Study Group. 2008. Sleep disordered breathing and hypertension: does selfreported sleepiness modify the association? Sleep 31. 1127–32.

ventilatory reserve. Thus, successful climbers, having adopted a more efficient breathing (i.e., allowing to maintain sufficient blood oxygenation with less work) maintained lower sensitivity to hypoxia during acclimatisation, but consequently retained higher available reserve for the summit. Ventilatory efficiency may be important in preventing excessive increases in ventilation, thus allowing a sustainable ventilation at extreme hypoxia, despite a relatively reduced ventilatory drive. These findings confirm that appropriate manipulations of ventilatory pattern may favorably modify the cardio-respiratory control and provide important benefits under critical – environmental or pathologic – conditions.

doi:10.1016/j.autneu.2009.05.065

doi:10.1016/j.autneu.2009.05.066

S13.2 Chemo-baroreflex interactions at high altitude and during respiratory conditioning

S13.3 Chronic and transient baroreflex dysfunction: A human case series

L. Bernardi (Department of Internal Medicine, University of Pavia and IRCCS S.Matteo, 27100 Pavia, Italy)

D.L. Jardine (Department of General Medicine, Christchurch Hospital, Christchurch, NZ)

Hypobaric hypoxia (typically occurring during exposure to high altitude) induces short- and long-term modifications the cardiorespiratory control, characterised by a decrease in the baroreflex sensitivity and by an increase in chemoreflex sensitivity, as part of the normal acclimatisation process. However, similar modifications in the control of the cardio-respiratory systems are also an early sign of autonomic dysfunction in several important cardiovascular (particularly heart failure) and also respiratory diseases. Thus, research on technique of adaptation to high altitude could benefit our understanding of pathologic mechanisms occurring at sea level. One important aspect of the cardio-respiratory interaction, is the possibility of using respiration (which is both under volitional and autonomic control), to modulate the autonomic nervous system and shift the balance between excitatory (sympathetic) and inhibitory (parasympathetic) influences. The practice of slow and deep breathing, as can be obtained by yoga-derived respiratory techniques, can increase resting oxygen saturation at high altitude. This was shown in experiments during simulated altitude and during high altitude expeditions, when subjects practicing this type of breathing (yoga trainees) were able to maintain an adequate oxygen saturation despite a reduced minute ventilation and reduced ventilatory drive. In turn, this reduced ventilation maintained a higher baroreflex sensitivity and parasympathetic activity, same as it was found in Himalayan subjects well adapted to high altitude. Application of this technique to patients with heart failure resulted in improved blood oxygenation, improved autonomic balance and increased exercise tolerance. However, the extent and the relevance of this effect on work performance at altitude remains unclear. We then tested whether higher ventilation and higher hypoxic ventilatory drive were necessary prerequisites to reach extreme altitudes (Everest or K2 summits) without oxygen. We studied 11 elite climbers (2004 Italian Expedition to Everest and K2) — at sea level, after arriving at the Everest base camp (5200 m), and after 9-day acclimatisation, by measuring resting cardiovascular and ventilatory control parameters. Thereafter, five climbers reached one or both summits without oxygen support, whereas the other 6 did not (4 subjects) or used oxygen (2 subjects). While at sea level and at upon arrival at altitude all variables were similar in the two groups, after the initial acclimatisation period the successful climbers differed from the other subjects: minute ventilation, breathing rate and hypoxic ventilatory drive were lower in these subjects, whereas ventilatory efficiency, ventilatory reserve and baroreflex sensitivity were higher. The ventilatory efficiency correlated with the indices of

Most reported cases of chronic baroreflex failure have occurred following carotid body tumour resection, bilateral carotid endartectomy or neck irradiation. These patients have presented with symptoms of excess sympathetic nerve activity, labile hypertension and extreme sensitivity to anti-hypertensive drugs. Case (A) below, is a typical example but in the remainder [Cases B–E] the clinical findings were different, depending on aetiology and what other parts of the nervous system were involved. (A) A 75-yr-old man presented following a collapse [1]. He had previously undergone neck radiotherapy for squamous cell carcinoma of the right external auditory canal. On examination he had ipsilateral lower motor neurone facial weakness and vocal chord paralysis. Continuous BP (blood pressure), HR (heart rate) and MSNA (muscle sympathetic nerve activity) demonstrated increased baseline levels but decreased responses to deep breathing, Valsalva, and nitroprusside injection. (B) A 48-yr-old woman who presented with hoarseness, dysphagia and postural hypotension and was found to have mediastinal lymphadenopathy secondary to sarcoidosis [2]. HR and MSNA levels were increased at rest but responses to deep breathing, tilt and Valsalva were decreased. (C) A 75-yr-old woman presented with an acute left-sided lateral medullary syndrome following a stroke, and was noted to have episodes of labile hypertension, headache and diaphoresis after [passive] changes in posture [3]. MSNA levels were high, and normal inverse correlation between burst amplitude and diastolic BP was absent. (D) A 48-yr-old man presented with abdominal pain and on examination had resting tachycardia and postural hypotension [4]. CT abdomen demonstrated jejunal intususception and right renal infarction. Urinary and faecal porphyrin levels were raised and variegate porphyria was diagnosed. During the acute illness, BP, HR and MSNA baseline levels were increased, and responses to deep breathing, tilt and Valsalva were decreased compared to recordings obtainedafter recovery. (E) A 17-yr-old woman presented with mild peripheral neuropathy and anorexia. On examination she had Holmes–Adie pupils, resting tachycardia and postural hypotension [5]. Testing for antineuronal [ANNA-1] autoantibodies was positive and she was subsequently found to have a neuroblastoma in her right neck. Baseline HR and MSNA levels were increased but responses to tilt were impaired. Transient baroreflex dysfunction may occur during vasovagal syncope, rapid-eye-movement sleep and certain types of seizure.