The Effects of Ketamine on Renal Sympathetic Nerve Activity and Phrenic Nerve Activity in Rabbits (with Vagotomy) With and Without Afferent Inputs from Peripheral Receptors

Abstract

One reason for the reported conflicting results of the effect of ketamine on hemodynamics and respiration may be variations in afferent inputs from peripheral receptors to the central nervous system. In order to evaluate unmasked direct effects of ketamine on sympathetic nerve and phrenic nerve outflow, totally deafferented (involving vagus, sinus nerve, aortic depressor nerve) rabbits (n = 18), rabbits with vagotomy (n = 21), and neuraxis-intact rabbits (n = 6) were used in this study. The animals were anesthetized with urethane and mechanically ventilated. Ketamine 0.5, 1, or 2 mg/kg was injected intravenously and mean arterial pressure (MAP), heart rate (HR), and integrated renal sympathetic nerve and phrenic nerve activity (IRSNA, IPNA) were recorded before, and 1, 2, 3, 5, and 10 min after injection. MAP and IRSNA were significantly decreased, even by the smallest dose of ketamine, in the totally deafferented group. IPNA was decreased by the largest dose of ketamine only in the totally deafferented group. On the other hand, spontaneous respiratory frequency was decreased in the totally deafferented and vagotomy groups, but more so in the totally deafferented group. In the neuraxis-intact group, the only significant change with the largest dose of ketamine, 2 mg/kg was a slight increase in HR. We conclude that ketamine can suppress vasomotor and respiratory centers directly, and that the suppression is counterbalanced by afferent inputs from peripheral receptors.

Ketamine Differentially Blocks Sensory Afferent Synaptic Transmission in Medial Nucleus Tractus Solitarius (mNTS)

“…4,17,18 Interestingly, elimination of baroreceptor afferent inputs by sinoaortic denervation attenuated the cardiovascular responses to ketamine, suggesting that such afferents play a role in the pressor actions of ketamine. 17,35 Bradycardic responses to activation of the peripheral cut end of the cardiac vagus nerve were unaltered by ketamine, suggesting that their peripheral function and cardiac responsiveness are preserved and that more central mechanisms are responsible for cardiac parasympathetic inhibition during ketamine. 4 Together, these studies of intact animals suggest that inhibition of afferent synaptic transmission in mNTS could be a mechanism of action of ketamine.…”

“…For example, A-and C-type nodose neurons differ substantially in their expression of tetrodotoxin-sensitive and -resistant Na ϩ currents, 39,46 and ketamine (IC 50 ϭ 200 M) depresses tetrodotoxin-sensitive sodium uptake in brain. 35 Peripheral nerve axonal sodium channels are more sensitive to ketamine than voltage dependent potassium channels (IC 50 Ϸ 300 vs. Ͼ 940 M). 47 However, the inhibition of potassium channels in neuroblastoma cells by ketamine at clinical concentrations has been correlated to anesthetic actions.…”

Blunted functional responses to pre- and postjunctional sympathetic stimulation in hibernating myocardium

“…This anesthetic regimen was specifically chosen to minimize effects on the sympathetic nervous system. Although at high doses, both ketamine and propofol have been shown to alter autonomic responses, effects at low-to-moderate doses are minimal and opposed (36,43).…”

Role of Muscarinic Cholinergic Transmission in Edinger-Westphal Nucleus-induced Choroidal Vasodilation in Pigeon

“…Studies of the modulatory effects of ketamine, which was used as anesthetic in our experiments, on cardiovascular and autonomic systems has yielded conflicting results (Yamamura, Kimura and Furukawa, 1983 ;Sasao et al, 1996). Cardiostimulatory effects of ketamine have been emphasized as a unique feature of this anesthetic agent (Murray, 1994).…”