Augmentation of Left Ventricular Contractility by Cardiac Sympathetic Neural Stimulation

Abstract

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. 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. 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.