title: Augmentation of left ventricular contractility by cardiac sympathetic neural stimulation.
abstract: BACKGROUND
  Electric stimulation of mediastinal sympathetic cardiac nerves increases cardiac contractility but is not selective for the left ventricle because it elicits sinus tachycardia and enhanced atrioventricular conduction. The aim of this study was to identify sympathetic neural structures inside the heart that selectively control left ventricular inotropy and can be accessed by transvenous catheter stimulation.
  
  
  RESULTS
  In 20 sheep, high-frequency stimulation (200 Hz) during the myocardial refractory period with electrode catheters inside the coronary sinus evoked a systolic left ventricular pressure increase from 97+/-20 to 138+/-32 mm Hg (P<0.001) without changes in sinus rate or PR time. Likewise, the rate of systolic pressure development (1143+/-334 versus 1725+/-632 mm Hg/s; P=0.004) and rate of diastolic relaxation (531+/-128 versus 888+/-331 mm Hg/s; P=0.001) increased. The slope of the end-systolic pressure-volume relationship increased (2.3+/-0.8 versus 3.1+/-0.6 mm Hg/mL; P=0.04), as did cardiac output (3.5+/-0.8 versus 4.4+/-0.8 L/min; P<0.001). Systemic vascular resistance and right ventricular pressure remained unchanged. There was a sigmoid dose-response curve. Ultrasound analysis revealed an increase in circumferential and radial strain in all left ventricular segments that was significant for the posterior, lateral, and anterior segments. Pressure effects were maintained for at least 4 hours of continued high-frequency stimulation and abolished by beta1-receptor blockade. Histology showed distinct adrenergic nerve bundles at the high-frequency stimulation site.
  
  
  CONCLUSIONS
  Cardiac nerve fibers that innervate the left ventricle are amenable to transvenous electric catheter stimulation. This may permit direct interference with and modulation of the sympathetic tone of the left ventricle.
authors.affiliation: Division of Cardiology, RWTH-Aachen University, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
authors.forename: Obaida R
authors.initials: OR
authors.lastname: Rana
authors.forename: Erol
authors.initials: E
authors.lastname: Saygili
authors.forename: Christopher
authors.initials: C
authors.lastname: Gemein
authors.forename: Michael
authors.initials: M
authors.lastname: Becker
authors.forename: Kay W
authors.initials: KW
authors.lastname: Nolte
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Thomas
authors.initials: T
authors.lastname: Schimpf
authors.forename: Christian
authors.initials: C
authors.lastname: Knackstedt
authors.forename: Karl
authors.initials: K
authors.lastname: Mischke
authors.forename: Rainer
authors.initials: R
authors.lastname: Hoffmann
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.forename: Dainius
authors.initials: D
authors.lastname: Pauza
authors.forename: Patrick
authors.initials: P
authors.lastname: Schauerte
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002404:Catheterization; D004558:Electric Stimulation; D004566:Electrodes; D006352:Heart Ventricles / Q000294:innervation*; D023421:Models, Animal; D009200:Myocardial Contraction / Q000502:physiology*; D012756:Sheep; D013564:Sympathetic Nervous System / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology*