|Green, Benedict - Ben|
|Pfister, James - Jim|
Submitted to: American Journal of Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2008
Publication Date: 4/4/2009
Citation: Green, B.T., Pfister, J.A., Cook, D., Welch, K.D., Stegelmeier, B.L., Lee, S.T., Gardner, D.R., Knoppel, E.L., Panter, K.E. 2009. Effects of Larkspur (Delphinium barbeyi) on Heart Rate and Electrically Evoked Electromyographic Response of the External Anal Sphincter in Cattle. American Journal of Veterinary Research. 70(4):539-546 Interpretive Summary: This is a transdisciplinary study on the dose-related effects of toxic larkspur alkaloids on heart rate and voluntary muscle contractility in beef cattle. Toxic larkspur (Delphinium) species have been responsible for large losses to the cattle industry in Western North America and are a serious economic problem. The present study tested the hypothesis that toxic larkspur produces changes in heart rate and external anal sphincter tone after its ingestion in cattle, and that these effects can be mitigated by inhibitors of acetylcholinesterase. The toxic larkspur alkaloids produced dose-dependent changes in heart rate and voluntary muscle contractility 24 hours after oral administration. The acetylcholinesterase inhibitor neostigmine significantly reduced the tachycardia seen at 24 hours when given at a dose of 0.04 mg/kg i.v. Neostigmine at a dose of 0.02 mg/kg i.m. was used to “rescue” intoxicated animals in recumbency. Reversal of recumbency, and most importantly, lateral recumbency by the use of neostigmine may provide a means to alter the medical outcome of larkspur poisoning in beef cattle.
Technical Abstract: Norditerpenoid alkaloids of larkspur (Delphinium spp.) are competitive antagonists of nicotinic cholinergic receptors and poison cattle with, high mortality. Of the norditerpenoids, the N-(methylsuccinimido) anthranoyllycoctonine type (MSAL-type) alkaloids are most toxic. This study tested the hypothesis that MSAL-type alkaloids in larkspur produce sub-acute effects of on heart rate and external anal sphincter tone which can be surmounted by inhibitors of acetylcholine breakdown in cattle. Dried, finely ground larkspur was administered by oral gavage in a range of doses equivalent to 0.5 - 11.8 mg/kg of MSAL-type alkaloids. Larkspur-treated cows manifested dose-related increases in heart rate and decreases in sphincter tone. The cholinesterase inhibitor neostigmine, which increases acetylcholine concentrations at neuromuscular synapses, significantly decreased heart rate but had no effect on voluntary muscle tone after it was given i.v. at 24 hours after oral administration of 10.4 mg/kg MSAL-type alkaloids. The related anticholinesterase drug, physostigmine had no effect on heart rate but doubled muscle tone. Neostigmine (0.02 mg/kg, i.m.) rapidly reversed the effects of 14.5 mg/kg of the MSAL-type alkaloids, a dose which induced sternal or lateral recumbency in animals. These results suggest that norditerpenoid alkaloids affect multiple nicotinic cholinergic receptors and alter neurotransmission at autonomic ganglia and the neuromuscular junction. Furthermore, neostigmine appears to be effective in reversing the acute neuromuscular and cardiac effects and the longer-term cardiac actions of toxic larkspur alkaloids.