Quantifying the altered cardiac response to atropine following pyridostigmine in rhesus macaques

An estimate of the amplitude of respiratory sinus arrhythmia (V̂) has been proposed as a noninvasive measure of parasympathetic activity. This experiment monitored V̂ in response to a subclinical dose of pyridostigmine bromide (PYR) and a pharmacological challenge of atropine sulfate (ATR). Twelve male rhesus macaques received 200 μg/kg of PYR 30 min prior to an injection of 0, 14, 44, or 140 μg/kg ATR. The decrease in V̂ after both the 44 and 140 μg/kg ATR doses was similar to the response to ATR alone in a previous experiment. The 14 μg/kg dose of ATR did not significantly decrease V̂ in this experiment, which is in contrast with the large decrease of V̂ after ATR alone in a previous experiment. Neither drug affected respiration. The dose of ATR which would be effective in causing a 30% decrease of V̂ in the presence of PYR was estimated to be 18.3 μg/kg of ATR. This is twice the dose of ATR calculated to have the same effect without PYR. The attenuated response of V̂ after a pharmacological challenge of ATR may be used to quantify the latent muscarinic effects from exposure to anticholinesterase agents. The attenuated response to ATR may also be useful for evaluating the return of normal cholinergic function after disruption by cholinesterase inhibitors.