Introduction: Manipulation of cardiovascular performance by electrical stimulation of the brain has been demonstrated in animals and humans. One such site is the mesencephalic locomotor region, formed by the rostral part of the pedunculopontine nucleus (PPN). Dysautonomia is common in Parkinson’s disease and up to 50% of patients suffer from orthostatic hypotension which can be severely debilitating. The aim of this study was to test whether PPN stimulation could modulate the postural cardiovascular response to head-up tilt. Methods: Patients with in-dwelling bilateral PPN electrodes underwent 80 degree head-up tilt testing with stimulation On and Off, in random order. Percentage change in systolic blood pressure during the first three minutes of tilting was the primary outcome variable. Secondary cardiovascular variables were recorded to indicate the mechanism of any blood pressure changes. Results: Fall in systolic blood pressure after tilt was significantly smaller with PPN stimulation than without (mean -8.3% versus -17.2%, t=2.679, df=5, p=0.044 using paired samples t-tests). A similar increase in heart rate of 10% occurred in both conditions. dP/dt, a surrogate marker of cardiac contractility, and pulse pressure, a surrogate marker of peripheral vascular resistance, were maintained better with stimulation (p=0.018 and 0.030, respectively). Baroreceptor reflex sensitivity decreased significantly with stimulation (z=-1.992, p=0.046 using Wilcoxon signed ranks test). Analysis of the electrocardiogram at rest revealed no changes in the On compared to Off states in RR-interval, PR-interval or QT variability (n=10, p=0.697, p=0.952 and p=0.897, respectively using paired samples t-tests). Conclusions: PPN stimulation can modulate the cardiovascular response to head-up tilt in humans. The PPN appears to be influencing systolic blood pressure by increasing peripheral vascular tone and cardiac contractility in addition to alteration of the baroreceptor reflex itself. The mechanism of blood pressure maintenance by PPN stimulation does not appear to be via detectable chronotropic effects.
University of Oxford (2011) Proc Physiol Soc 23, PC44
Poster Communications: Manipulation of the cardiovascular response to postural challenge by pedunculopontine nucleus stimulation in humans
J. A. Hyam1,2, W. Thevathasan3, S. Wang1, G. Kerr4, A. Rojek4, I. Stewart4, J. F. Stein1, T. Coyne5, P. Silburn6, D. J. Paterson1, T. Z. Aziz1,2, A. L. Green1,2
1. Department of Physiology, Anatomy & Genetics, Univ Oxford, Oxford, United Kingdom. 2. Department of Neurosurgery, University of Oxford, Oxford, United Kingdom. 3. Nuffiled Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom. 4. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. 5. Department of Neurosurgery, St. Andrews & Wesley Hospitals, Brisbane, Queensland, Australia. 6. Centre for Clinical Research, Royal Brisbane and Women's Hospital, University of Queensland, Brisbane, Queensland, Australia.
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