Inspiratory coupling to cardiac activity and to somatic afferent nerve stimulation in the anaesthetised rat P.D. Larsen * , Y.C. Tzeng, D.C. Galletly Department of Surgery and Anaesthesia, Wellington School of Medicine, P.O. Box 7343, Wellington, New Zealand Received 10 June 2003; accepted 22 August 2003 Abstract We examined the ability of somatic afferent nerve stimulation to entrain inspiratory onset in the anaesthetized spontaneously breathing rat, and compared features of this stimulus–ventilatory coupling to entrainment of inspiratory onset by cardiac activity. In 14 rats prior to stimulation, we commonly observed a constant temporal alignment between ECG R waves and inspiratory onset (cardioventilatory coupling). Stimulation of a hamstring nerve at rates close to the heart rate also caused coupling (a constant stimulus to inspiratory onset interval), although this was highly dependent upon frequency of stimulation, with small changes in frequency causing a loss of coupling. In experiments where stimuli were given at constant intervals after ECG R waves, we observed no augmentation of coupling. Our results indicate that both cardiac and somatic afferent nerve activity is able to entrain inspiratory onset. We have suggested that coupling causes respiratory frequency to increase, and it is possible that this is a general mechanism whereby non-respiratory afferents act as stimulants or pacemakers to respiratory rhythm. The role of non-respiratory activity in initiating inspiration needs to be more fully recognised and studied. D 2003 Elsevier B.V. All rights reserved. Keywords: Inspiratory coupling; Cardiac activity; Somatic afferent nerve stimulation 1. Introduction An important property of biological oscillators is that they can be triggered or entrained by periodic inputs from either the external or internal environment (Ermentrout and Rinzel, 1984; Petrillo and Glass, 1984; Guevara et al., 1988; Glass, 2001). We have previously demonstrated that respiratory activity can become temporally linked to heart beat timing in anaesthetized, spontaneously breathing rats (Larsen and Galletly, 1999), as well as in human subjects (Galletly and Larsen, 1997a,b, 1999; Larsen et al., 1999), and we have termed this cardioventilatory coupling. We have shown that during cardioventilatory coupling there is a constant time interval between inspiration and the immediately preceding heart beat, and suggested that this synchronization is due to a cardiovascular neural afferent arising as a result of that heart beat producing an input to the central respiratory oscillators that facilitates the onset of inspiration (Galletly and Larsen, 1997b; Larsen et al., 1999). We have created a simple computer model based on this premise, which reproduces the complex patterns of coupling between heart beats and inspiration that are observed experimentally (Galletly and Larsen, 2001). Respiratory rhythm can become synchronised to stimuli other than the heart rhythm. Various groups have demon- strated synchronisation of breathing to exercise (Iscoe, 1981), periodic electrical stimulation of the nucleus para- brachialis medialis (Cohen and Feldman, 1977), and peri- odic electrical stimulation of somatic afferent nerves (Iscoe and Palosa, 1976; Kawahara et al., 1988). Iscoe and Palosa (1976) conducted experiments inves- tigating the synchronisation of respiratory timing to somat- ic afferent nerve stimulation in anaesthetised cats. They observed that a single stimulus delivered during expiration was capable of advancing the onset of the following inspiration, and that when inspiration was advanced there was a constant stimulus to inspiration time interval. They observed that in response to brief periods of repetitive stimulation respiratory frequency could become locked in whole number ratio to the stimulus frequency, again with a constant time interval between stimulus and inspiratory 1566-0702/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.autneu.2003.08.007 * Corresponding author. Tel.: +64-4-385-5999; fax: +64-4-389-5318. E-mail address: peter.larsen@wnmeds.ac.nz (P.D. Larsen). www.elsevier.com/locate/autneu Autonomic Neuroscience: Basic and Clinical 108 (2003) 45 – 49