Preliminary observations on the vasomotor responses to electrical stimulation of the ventrolateral surface of the human medulla

Clinical article

Restricted access


Pulsatile arterial compression (AC) of the ventrolateral medulla (VLM) is hypothesized to produce the hypertension in a subset of patients with essential hypertension. In animals, a network of subpial neuronal aggregates in the VLM has been shown to control cardiovascular functions. Although histochemically similar, neurons have been identified in the retro-olivary sulcus (ROS) of the human VLM, but their function is unclear.


The authors recorded cardiovascular responses to electrical stimulation at various locations along the VLM surface, including the ROS, in patients who were undergoing posterior fossa surgery for trigeminal neuralgia. This vasomotor mapping of the medullary surface was performed using a bipolar electrode, with stimulation parameters ranging from 5- to 30-second trains (20–100 Hz), constant current (1.5–5 mA), and 0.1-msec pulse durations. Heart rate (HR) and blood pressure (BP) were recorded continuously from baseline (10 seconds before the stimulus) up to 1 minute poststimulus. In 6 patients, 17 stimulation responses in BP and HR were recorded.


The frequency threshold for any cardiovascular response was 20 Hz; the stimulation intensity threshold ranged from 1.5 to 3 mA. In the first patient, all stimulation responses were significantly different from sham recordings (which consisted of electrodes placed without stimulations). Repeated stimulations in the lower ROS produced similar responses in 3 other patients. Two additional patients had similar responses to single stimulations in the lower ROS. Olive stimulation produced no response (control). Hypotensive and/or bradycardic responses were consistently followed by a reflex hypertensive response. Slight right/left differences were noted. No patient suffered short- or long-term effects from this stimulation.


This stimulation technique for vasomotor mapping of the human VLM was safe and reproducible. Neuronal aggregates near the surface of the human ROS may be important in cardiovascular regulation. This method of vasomotor mapping with measures of responses in sympathetic tone (microneurography) should yield additional data for understanding the neuronal network that controls cardiovascular functions in the human VLM. Further studies in which a concentric bipolar electrode is used to generate this type of vasomotor map should also increase understanding of the pathophysiological mechanisms of neurogenically mediated hypertension, and assist in the design of studies to prove the hypothesis that it is caused by pulsatile AC of the VLM.

Abbreviations used in this paper:AC = arterial compression; BP = blood pressure; HR = heart rate; MAP = mean arterial pressure; ROS = retro-olivary sulcus; VLM = ventrolateral medulla.

Article Information

Address correspondence to: S. J. Patel, M.D., Department of Neuroscience, Medical University of South Carolina, Suite 428, 96 Jonathan Lucas Street, Charleston, South Carolina 29425. email:

Please include this information when citing this paper: published online April 27, 2012; DOI: 10.3171/2012.3.JNS11973.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    A–C: Graphs showing Δ MAP and Δ HR during and after stimulation of the inferior ROS in a 77-year-old man with no history of hypertension, demonstrating a stimulation cardiovascular response threshold at 20 Hz and increased response magnitude with higher pulse train frequencies up to 100 Hz, 3–5 V, 0.1-msec pulse duration. D: Also shown is the lack of cardiovascular response with stimulation of the olivary surface. bpm = beats per minute; Δ HR = change in HR; Δ MAP = change in MAP.

  • View in gallery

    Graphs showing Δ MAP and Δ HR during and after stimulation of the inferior ROS in a 65-year-old woman. Left: A 30-second stimulation at 3 mA, with 0.1-msec pulses at 100 Hz. Right: A 5-second stimulation at 4.5 mA.

  • View in gallery

    A schematic depiction of the medullary surface in the region of the ROS. O. = olive.



Aicher SAReis DJ: Gigantocellular vasodepressor area is tonically active and distinct from caudal ventrolateral vasodepressor area. Am J Physiol 272:R731R7421997


Aicher SASaravay RHCravo SJeske IMorrison SFReis DJ: Monosynaptic projections from the nucleus tractus solitarii to C1 adrenergic neurons in the rostral ventrolateral medulla: comparison with input from the caudal ventrolateral medulla. J Comp Neurol 373:62751996


Akimura TFurutani YJimi YSaito KKashiwagi SKato S: Essential hypertension and neurovascular compression at the ventrolateral medulla oblongata: MR evaluation. AJNR Am J Neuroradiol 16:4014051995


Chung KSSinatra RSHalevy JDPaige DSilverman DG: A comparison of fentanyl, esmolol, and their combination for blunting the haemodynamic responses during rapid-sequence induction. Can J Anaesth 39:7747791992


Ciofolo MJReiz S: Circulatory effects of volatile anesthetic agents. Minerva Anestesiol 65:2322381999


Coffee RENicholas JSEgan BMRumboldt ZD'Agostino SPatel SJ: Arterial compression of the retro-olivary sulcus of the medulla in essential hypertension: a multivariate analysis. J Hypertens 23:202720312005


Cohn JNFinkelstein SMcVeigh GMorgan DLeMay LRobinson J: Noninvasive pulse wave analysis for the early detection of vascular disease. Hypertension 26:5035081995


Colón GPQuint DJDickinson LDBrunberg JAJamerson KAHoff JT: Magnetic resonance evaluation of ventrolateral medullary compression in essential hypertension. J Neurosurg 88:2262311998


Cravo SLMorrison SFReis DJ: Differentiation of two cardiovascular regions within caudal ventrolateral medulla. Am J Physiol 261:R985R9941991


Dampney RAGoodchild AKRobertson LGMontgomery W: Role of ventrolateral medulla in vasomotor regulation: a correlative anatomical and physiological study. Brain Res 249:2232351982


Daniel MLarson MDEger EI IINoorani MWeiskopf RB: Fentanyl, clonidine, and repeated increases in desflurane concentration, but not nitrous oxide or esmolol, block the transient mydriasis caused by rapid increases in desflurane concentration. Anesth Analg 81:3723781995


Dickerson LWPanico WHKuhn FEWillis ACFitzgerald JFMeyer EL: Stimulation of dog RVLM and A5 area changes sympathetic outflow to vascular beds without effect on the heart. Am J Physiol 272:R821R8391997


Dormer KJBedford TG: Cardiovascular control by the rostral ventrolateral medulla in the conscious dog. Prog Brain Res 81:2652771989


Fein JMFrishman W: Neurogenic hypertension related to vascular compression of the lateral medulla. Neurosurgery 6:6156221980


Gajjar DEgan BCurè JRust PVanTassel PPatel SJ: Vascular compression of the rostral ventrolateral medulla in sympathetic mediated essential hypertension. Hypertension 36:78822000


Gandevia SCHales JP: The methodology and scope of human microneurography. J Neurosci Methods 74:1231361997


Geiger HNaraghi RSchobel HPFrank HSterzel RBFahlbusch R: Decrease of blood pressure by ventrolateral medullary decompression in essential hypertension. Lancet 352:4464491998


Halliday GMLi YWJoh THCotton RGHowe PRGeffen LB: Distribution of monoamine-synthesizing neurons in the human medulla oblongata. J Comp Neurol 273:3013171988


Illingworth RDPorter DGJakubowski J: Hemifacial spasm: a prospective long-term follow up of 83 cases treated by microvascular decompression at two neurosurgical centres in the United Kingdom. J Neurol Neurosurg Psychiatry 60:72771996


Jannetta PJSegal RWolfson SK Jr: Neurogenic hypertension: etiology and surgical treatment. Part I Observations in 53 patients. Ann Surg 201:3913981985


Jannetta PJSegal RWolfson SK JrDujovny MSemba ACook EE: Neurogenic hypertension: etiology and surgical treatment. Part II Observations in an experimental nonhuman primate model. Ann Surg 202:2532611985


Johnson RDHubscher CH: Brainstem microstimulation activates sympathetic fibers in pudendal nerve motor branch. Neuroreport 11:3793822000


Legrady PVoros EBajcsi DSonkodi SBarzo PAbraham G: Neurovascular pulsatile compression and neurosurgical decompression of the rostral ventrolateral medulla in medically resistant hypertensive patients. Kidney Blood Press Res 31:4334372008


Levy EIClyde BMcLaughlin MRJannetta PJ: Microvascular decompression of the left lateral medulla oblongata for severe refractory neurogenic hypertension. Neurosurgery 43:191998


Levy EIScarrow AMJannetta PJ: Microvascular decompression in the treatment of hypertension: review and update. Surg Neurol 55:2112001


Maiorov DNWilton ERBadoer EPetrie DHead GAMalpas SC: Sympathetic response to stimulation of the pontine A5 region in conscious rabbits. Brain Res 815:2272361999


Marano GGrigioni MTiburzi FVergari AZanghi F: Effects of isoflurane on cardiovascular system and sympathovagal balance in New Zealand white rabbits. J Cardiovasc Pharmacol 28:5135181996


Morimoto SSasaki SMiki SKawa TItoh HNakata T: Pulsatile compression of the rostral ventrolateral medulla in hypertension. Hypertension 29:5145181997


Naraghi RGaab MRWalter GFKleineberg B: Arterial hypertension and neurovascular compression at the ventrolateral medulla. A comparative microanatomical and pathological study. J Neurosurg 77:1031121992


Naraghi RGeiger HCrnac JHuk WFahlbusch REngels G: Posterior fossa neurovascular anomalies in essential hypertension. Lancet 344:146614701994


Natarajan MMorrison SF: Sympathoexcitatory CVLM neurons mediate responses to caudal pressor area stimulation. Am J Physiol Regul Integr Comp Physiol 279:R364R3742000


Nicholas JSD'Agostino SJPatel SJ: Arterial compression of the retro-olivary sulcus of the ventrolateral medulla in essential hypertension and diabetes. Hypertension 46:9829852005


Pagani MRimoldi OMalliani A: Low-frequency components of cardiovascular variabilities as markers of sympathetic modulation. Trends Pharmacol Sci 13:50541992


Ross CARuggiero DAPark DHJoh THSved AFFernandez-Pardal J: Tonic vasomotor control by the rostral ventrolateral medulla: effect of electrical or chemical stimulation of the area containing C1 adrenaline neurons on arterial pressure, heart rate, and plasma catecholamines and vasopressin. J Neurosci 4:4744941984


Rovit RLMurali RJannetta PJ: Trigeminal Neuralgia BaltimoreWilliams & Wilkins1990


Thuerl CRump LCOtto MWinterer JTSchneider BFunk L: Neurovascular contact of the brain stem in hypertensive and normotensive subjects: MR findings and clinical significance. AJNR Am J Neuroradiol 22:4764802001


Verberne AJSartor DMBerke A: Midline medullary depressor responses are mediated by inhibition of RVLM sympathoexcitatory neurons in rats. Am J Physiol 276:R1054R10621999


Watkins LLGrossman PSherwood A: Noninvasive assessment of baroreflex control in borderline hypertension. Comparison with the phenylephrine method. Hypertension 28:2382431996


Watters MRBurton BSTurner GECannard KR: MR screening for brain stem compression in hypertension. AJNR Am J Neuroradiol 17:2172211996


Yamamoto IYamada SSato O: Microvascular decompression for hypertension—clinical and experimental study. Neurol Med Chir (Tokyo) 31:161991


Zizka JCeral JElias PTintera JKlzo LSolar M: Vascular compression of rostral medulla oblongata: prospective MR imaging study in hypertensive and normotensive subjects. Radiology 230:65692004




All Time Past Year Past 30 Days
Abstract Views 43 43 14
Full Text Views 84 84 5
PDF Downloads 124 124 5
EPUB Downloads 0 0 0


Google Scholar