Renal Nerve Stimulation for Treatment of Neurocardiogenic Syncope Malini Madhavan, M.B.B.S. Division of Cardiovascular Diseases Mayo Clinic, Rochester, MN test

Neurocardiogenic Syncope: Need for Novel Therapies Syncope in the USA 3% ER visits, 6% hospital admissions $ 2.4 billion / year Neurocardiogenic syncope - 22% prevalence No uniformly effective therapy for recurrent neurocardiogenic syncope Pacemaker implantation Recurrence of syncope in 30% Ann Intern Med. 2000;133:714-725; BMJ 2004;329:336-41; JAMA 2003;289:2224-9

Neurocardiogenic Syncope: Mechanism Trigger Vagal efferents Bradycardia Sympathetic efferents Vasodilation ↓Ventricular filling ↑Inotropy ↑Cardiac mechanoreceptors ↓Vascular baroreceptors Vascular centers in Medulla ↑Vagal output Bradycardia Sympathetic withdrawal Vasodilation Effective Rx

Renal Sympathetic Innervation: Efferents Nucleus tractus solitarius Rostral ventrolateral medulla Hypothalamus T5-L2 ↑ Renin Sodium retention Renal vasoconstriction ↑ BP Celiac, Superior mesenteric, Aorticorenal ganglia Renal A

Renal Sympathetic Innervation: Afferents ↑ Central sympathetic output Vasoconstriction ↑ Heart rate ↑ Blood pressure Renal pelvis T12 – L3 Nucleus tractus solitarius Rostral ventrolateral medulla Hypothalamus

Renal Denervation Renal denervation – sustained ↓ Blood pressure ↓ Central sympathetic output ↓ Muscle sympathetic nerve activity ↓ Whole body and renal norepinephrine spill- over

Hypotheses Stimulation of the renal sympathetic nerves increases blood pressure Electrical stimulation from the renal vein can stimulate the renal nerves Close proximity of renal vein, artery and nerves

Aim To assess the effect of high frequency electrical stimulation of renal nerves from the renal vein on blood pressure in animals

Methods Dogs (n=5) Baboon (n=1) Isoflurane anesthesia Renal artery and vein angiogram

Methods Quadripolar catheter (4mm tip, 2mm electrode spacing) Unilateral renal vein High frequency stimulation (800-900 pps, 10V, 30- 200s, Grass stimulator)

BP During Renal Vein Stimulation in the Canine 100 200 Blood Pressure (mmHg) Stimulation Rapid and sustained rise in blood pressure

Change in Systolic Blood Pressure during Renal Vein Stimulation

Renal Vein Stimulation: Change in Blood Pressure Systolic BP Diastolic BP Median (IQ) 11(5 – 22) mmHg Median (IQ) 6 (-2 – 16) mmHg

Conclusions Electrical stimulation of renal nerves through the renal vein Sustained ↑ in systolic BP in the canine and baboon Proposed mechanism ↑ Central sympathetic output Potential applications Neurocardiogenic syncope Other reflex syncope Postoperative vasoplegia Diabetic dysautonomia leading to orthostatic hypotention Hypotensive states in the critically ill

Future Directions: Novel Device for Neurocardiogenic Syncope