Denervation of vagal cardiopulmonary receptors by injection of kainic acid into the nodose ganglia in dogs

We determined if kainic acid, a neuroexcitotoxin, could be used to denervate the cell bodies of cardiopulmonary vagal sensory neurons. Kainic acid (5 μg) was injected into the nodose ganglion of five dogs. Ten to fourteen days following this procedure, these kainic acid-injected dogs were anesthetized and tested for the extent of the deafferentation. Five additional dogs were used as the control group. Heart rate and mean arterial pressure were measured, and a Swan-Ganz catheter was advanced into a branch of the pulmonary artery to measure pulmonary capillary wedge pressure. We recorded renal sympathetic nerve activity from branches of the left renal nerves. Bilateral carotid occlusion increased heart rate and mean arterial pressure in only the denervated group, but sympathetic nerve activity increased significantly in both groups. This demonstrates that the carotid baroreflex is preserved after kainic acid is injected into the nodose ganglia. Volume expansion by use of warmed saline (15 ml kg−1) increased pulmonary capillary wedge pressure 5 mm Hg in control and 14 mm Hg in denervated dogs. In control dogs, sympathetic nerve activity decreased by 10% per mm Hg increase in pulmonary capillary wedge pressure while in denervated dogs, it decreased by 2% per mm Hg. This demonstrates that the vagal cardiopulmonary baroreflex is essentially abolished after injection of kainic acid into the nodose ganglia. After opening the chest, acetylstrophanthidin 100 μg was applied directly to the epicardial surface of the left ventricle to activate cardiac vagal afferents. Epicardial acetylstrophanthidin decreased sympathetic nerve activity by 28% in the control group, but resulted in no change in the kainic-acid-injected dogs. This demonstrates that vagal cardiac chemosensitive reflexes are abolished after bilateral injection of kainic acid into the nodose ganglia. At the end of these experiments, we removed the nodose ganglia for histological evaluation. The vast majority of cell bodies in the ganglia from the denervated group appeared injured compared to cell bodies in ganglia that had not been injected, suggesting that the destruction of cell bodies of vagal afferents was responsible for the functional denervation. Our findings are consistent with the interpretation that kainic acid treatment interrupts vagal afferents that meditate reflex responses to epicardial acetylstrophanthidin and to volume expansion.