888 June 2002 PACE, Vol. 25, No. 6 Introduction Overall cardiovascular performance is deter- mined by the complex interaction between ven- tricular systolic and diastolic function and the properties of the afterload and preload systems. 1 The atria are part of the preload system and serve three important roles as a conduit, reservoir, and contractile chamber. 2,3 Electrical pacing of the atria affects the pattern of atrial depolarization and contraction and may alter the mechanical in- teraction between the atria and ventricles (e.g., atrioventricular [AV] coupling). Acute and chronic changes in atrial geometry resulting from altered hemodynamics may also produce atrial tachyarrhythmias. 4,5 Thus, ideal atrial pacing tim- ing and location may enhance hemodynamic per- formance and theoretically prevent or attenuate the development of a proarrhythmic atrial sub- strate. Previous investigations have evaluated the dependence of ventricular performance on AV coupling. 6–10 In addition, the increased clinical use of active-fixation atrial pacing leads has stim- ulated exploration of alternative atrial lead loca- tions to prevent atrial arrhythmias. 11–15 The pre- sent investigation tested the hypothesis that atrial pacing lead location can change the dependence of left atrial (LA) and left ventricular (LV) hemo- dynamics on AV timing in dogs. Methods All procedures were reviewed and approved by an internal independent animal review com- mittee. All procedures conformed to the Guide for the Care and Use of Laboratory Animals [DHEW (DHHS) publication (NIH) no. 85-23, revised 1996]. Instrumentation Mongrel dogs of either sex (n 5 8, weight 26 6 2 kg) were anesthetized with intravenous propofol (8 mg/kg). After endotracheal intubation, anesthe- sia was maintained with isoflurane (1.65% end- Atrial Pacing Lead Location Alters the Effects of Atrioventricular Delay on Atrial and Ventricular Hemodynamics DOUGLAS A. HETTRICK, DAVID E. EULER, PAUL S. PAGEL,* SHAILESH K. MUSLEY, EDUARDO N. WARMAN, PAUL D. ZIEGLER, and RAHUL MEHRA Medtronic, Incorporated, Minneapolis, Minnesota and *Departments of Anesthesiology and Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin HETTRICK, D.A., ET AL.: Atrial Pacing Lead Location Alters the Effects of Atrioventricular Delay on Atrial and Ventricular Hemodynamics. The combined role of atrial pacing lead location and AV timing on cardiovascular performance has not been defined. This study tested the hypothesis that atrial pacing lead location can change the dependence of LA and LV hemodynamics on AV timing in vivo. Dogs anes- thetized with isoflurane (n 5 8) were instrumented for measurement of hemodynamics including LA pres- sure, LA volume, and pulmonary venous blood flow. Data were recorded during normal sinus rhythm, and atrial overdrive pacing from the right atrial appendage (RAA), proximal coronary sinus (CS), and LA lat- eral wall (LAW). The AV node was then ablated and measurements repeated during synchronous ven- tricular pacing and during dual chamber pacing from each atrial lead location at various AV delays (20, 60, 120, 180, 240, and 350 ms). Hemodynamics during intrinsic sinus rhythm and overdrive atrial pacing from different sites were similar. In contrast, ventricular or dual chamber pacing caused significant (P , 0.05) changes in cardiac output with different AV timing during RAA (3.5 6 0.2 vs 2.9 6 0.2 L/min at 120 and 350 ms, respectively) and LAW pacing but not CS pacing. A significant interaction between atrial lead location and AV delay was observed for changes in stroke volume, pulmonary venous blood transport, LA volume, and LV preload. The results indicate that the atrial contribution to cardiac output depends on AV timing and atrial lead location in isoflurane-anesthetized dogs with AV nodal conduction block. (PACE 2002; 25:888–896) atrial function, arrhythmia mechanisms, blood flow, hemodynamics, ventricular function Address for reprints: Douglas Hettrick, PhD, Staff Scientist, Ar- rhythmia Management Research T280, Medtronic, Inc., 7000 Central Ave. NE, Minneapolis, MN 55432. Fax: (763) 514-2701; e-mail: doug.hettrick 6medtronic.com Received April 10, 2001; revised June 7, 2001; accepted June 20, 2001. Reprinted with permission from JOURNAL OF PACING AND CLINICAL ELECTROPHYSIOLOGY , Volume 25, No. 6, June 2002 Copyright © 2002 by Futura Publishing Company, Inc., Armonk, NY 10504-0418.