To the Editor:
We felt our recent experience attempting to use atropine in a rat model would be informative for other investigators and refresh the literature on the subject. In preparation for research investigating the effects of intravenous lipid emulsion on Advanced Cardiac Life Support medications, we attempted to elucidate the proper dose of atropine to reliably cause cardiovascular effects in male Sprague Dawley rats weighing approximately 250 g. Performing our dose response experiment was necessary due to the equivocal results of previous literature on the subject. Junior et al.Citation1 used 2 mg/kg of intravenous atropine to blunt the presumed cholinergic cardiovascular effects of a cardiotoxin (a piperamide analog). However, older researchCitation2,Citation3 showed that smaller doses of atropine had no effects in a rat model while higher doses (up to 80 mg/kg) caused both tachycardia and bradycardia.
We found that isoflurane-anesthetized male Sprague Dawley rats had baseline heart rates of approximately 350 beats per minute (bpm) and a mean arterial pressure of approximately 80 mmHg. Rats treated with intravenous atropine at a dose of 2 mg/kg (n = 2) had no change in their heart rate and a 27.5 mmHg decrease in blood pressure. Using 10 mg/kg of atropine (n = 2) decreased their heart rate by 15 bpm and blood pressure by 38 mmHg. Rats treated with 20 mg/kg of atropine (n = 2) decreased their heart rate by 75 bpm and blood pressure by 47.5 mmHg. Although the decrease in heart rate from baseline was small and of questionable clinical significance, the expected effect of atropine infusion was tachycardia. At larger doses, the effect on blood pressure becomes clinically significant.
Given the bradycardia and the hypotension induced by atropine, we remind researchers involved with rats that atropine's effects are likely not related to its anticholinergic properties. Although the exact mechanisms of atropine's effects are unclear from our small pilot study, it is possible that atropine had a direct toxic effect on myocardial cells or acted directly on the central nervous system. In attempting to create an anticholinergic state in a rat model, we suggest using a different model or medication.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References
- de Araújo Junior JX, Julien C, Barres C, de Medeiros IA, Ribeiro EA, Lima LM, Barreiro EJ. Cardiovascular effects of a novel synthetic analogue of naturally occurring piperamides. J Cardiovasc Pharmacol 2010; 56:293–299 . doi:10.1097/FJC.0b013e3181ec061e.
- Kaplanski J, Weinhouse E, Martin O. Modification of digoxin induced arrhythmogenicity in adult rats following atropine administration. Res Commun Chem Pathol Pharmacol 1983; 39:173–176.
- Merrick A, Hadley W, Holcslaw T. The effect of large doses of atropine sulfate on heart rate and blood pressure in rats. Res Commun Chem Pathol Pharmacol 1979; 25:13–22.