-Fos expression in rat brain stem and spinal cord in response to activation of cardiac ischemia-sensitive afferent neurons and electrostimulatory modulation. Am J Physiol Heart Circ Physiol 287: H2728 -H2738, 2004. First published July 29, 2004 doi:10.1152/ajpheart.00180. 2004.-The purpose of this study was to identify central neuronal sites activated by stimulation of cardiac ischemia-sensitive afferent neurons and determine whether electrical stimulation of left vagal afferent fibers modified the pattern of neuronal activation. Fos-like immunoreactivity (Fos-LI) was used as an index of neuronal activation in selected levels of cervical and thoracic spinal cord and brain stem. Adult Sprague-Dawley rats were anesthetized with urethane and underwent intrapericardial infusion of an "inflammatory exudate solution" (IES) containing algogenic substances that are released during ischemia (10 mM adenosine, bradykinin, prostaglandin E2, and 5-hydroxytryptamine) or occlusion of the left anterior descending coronary artery (CoAO) to activate cardiac ischemia-sensitive (nociceptive) afferent fibers. IES and CoAO increased Fos-LI above resting levels in dorsal horns in laminae I-V at C2 and T4 and in the caudal nucleus tractus solitarius. Dorsal rhizotomy virtually eliminated Fos-LI in the spinal cord as well as the brain stem. Neuromodulation of the ischemic signal by electrical stimulation of the central end of the left thoracic vagus excited neurons at the cervical and brain stem level but inhibited neurons at the thoracic spinal cord during IES or CoAO. These results suggest that stimulation of the left thoracic vagus excites descending inhibitory pathways. Inhibition at the thoracic spinal level that suppresses the ischemic (nociceptive) input signal may occur by a short-loop descending pathway via signals from cervical propriospinal circuits and/or a longer-loop descending pathway via signals from the nucleus tractus solitarius. neuronal activation; coronary artery occlusion; intrapericardial algogenic solution; thoracic spinal cord; nucleus tractus solitarius; central nervous system MYOCARDIAL CHEMOSENSITIVE afferent neurons in nodose and dorsal root ganglia transduce the signals associated with regional ischemia to induce symptoms of angina (12, 13). The afferent pathways conducting the nociceptive signals from these cardiac ischemic sympathetic and vagal afferent fibers are well documented by electrophysiological studies using two models of cardiac "ischemia": intrapericardial infusion of algogenic substances and temporary occlusion of the left anterior descending artery.Several substances activate these cardiac chemosensitive neurons: bradykinin, substance P, prostaglandins, leukotrienes, lactate, potassium, and adenosine. It has been shown that the concentration of all these substances increases in the exudate solution of various animal models of ischemia (3-5, 13, 19, 25, 35, 40, 41). Models using occlusion of the left anterior descending coronary artery result in activation of cardiac sympathetic afferent fi...