Experimental Physiology : Translation and Integration Activity in vagal preganglionic motoneurones running to the heart provokes a generalized cardioinhibition producing a decrease not only in heart rate (chronotropy), but also in the rate of atrioventricular (AV) conduction (dromotropy), and in the force of myocardial contraction (inotropy). These effects are secondary to, and are contingent upon, excitation of ganglion cells located in clusters on the epicardium of the dorsum of the atria, closely apposed to the sites of entry of the major veins. There is evidence that in many of the larger mammalian species, the ganglion cells are clustered into discrete zones or ‘fat pads’ which project to different regions of the heart and selectively control cardiac function (Ardell & Randall, 1986; Randall et al. 1986a,b; Gatti et al. 1995, 1997). Several recent studies have described the anatomy of the cardiac vagal ganglia in the rat (Pardini et al. 1987; Abrahamian et al. 1991; Klimaschewski et al. 1992; Burkholder et al. 1992; deSouza et al. 1996; Cheng et al. 1999; Cheng & Powley, 2000). Although the results of some of these studies suggest the existence of a functional topography (e.g. Pardini et al. 1987), there is little clear physiological or pharmacological evidence of this in the rat. In the only previous study of a possible functional organization of rat cardiac ganglia (Burkholder et al. 1992), a brief description is given of a partial selectivity revealed by differing responses to vagal stimulation following local infiltration of hexamethonium into identified fat pads. Data from preliminary experiments in this laboratory suggest that glutamate excitation of cardiac vagal pre- ganglionic motoneurones from different regions of the rat nucleus ambiguus results in differential chronotropic and dromotropic effects (Sampaio et al. 2000). That this may result from a different termination pattern of preganglionic axons onto ganglion cells from different ganglionic clusters is supported by the finding of restricted ganglionic innervation from motoneurones labelled with anterograde Differential chronotropic and dromotropic responses to focal stimulation of cardiac vagal ganglia in the rat Karla N. Sampaio *, Hélder Mauad *, K. Michael Spyer and Timothy W. Ford † Autonomic Neuroscience Institute, Department of Physiology, Royal Free and University College Medical School, London NW3 2PF, UK and * Department of Physiological Sciences, Biomedical Center, Federal University of Espirito Santo, Vitoria, Brazil (Manuscript received 12 November 2002; accepted 25 January 2003) Vagal cardioinhibition is exerted through a reduction not only in the heart rate but also in the rate of propagation of the cardiac action potential and in myocardial contractility. In several species, such effects can be produced independently by selective activation of ganglia in identified ‘fat pads’. In this study we investigate differential control of heart rate and atrioventricular conduction by two ganglionic clusters in the rat, a species increasingly important in studies of cardiovascular control. Epicardial sites producing low-threshold changes in P–P and P–R interval of the ECG in an arterially perfused preparation were explored with concentric bipolar stimulating electrodes. Stimulation sites centred on two principal ganglia, the sinoatrial (SA) ganglion at the junction of the right superior vena cava and right atrium, and the atrioventricular (AV) ganglion at the junction of the inferior pulmonary veins and left atrium. Stimulation of the SA ganglion decreased heart rate in all preparations, with little or no effect on AV conduction in one-third. Stimulation of the AV ganglion consistently slowed conduction without eliciting a comparable bradycardia. Responses survived blockade of ganglionic transmission by trimetaphan, with an enhanced chronotropic selectivity to SA ganglion stimulation, suggesting that co-excitation of preganglionic elements en passant may have contributed to the earlier mixed responses. Effective stimulation sites were precisely circumscribed and corresponded to principal ganglionic clusters confirmed histologically. We conclude that cardiac vagal ganglia in the rat show a topographical functional organisation and are amenable to investigation using the arterially perfused preparation. Experimental Physiology (2003) 88.3, 315–327. 2525 Publication of The Physiological Society † Corresponding author: tford@rfc.ucl.ac.uk ) by guest on May 24, 2011 ep.physoc.org Downloaded from Exp Physiol (