Upstream eventCardiovascular dysregulation
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding|
|Acetylcholinesterase inhibition leading to acute mortality||adjacent||Low||Low|
Life Stage Applicability
Key Event Relationship Description
Dysregulation of heart rate and vascular tone leading to respiratory distress or arrest has been proposed in some species. In fish, acetylcholinesterase inhibition studies have led to the proposal that oxygen availability is reduced as a consequence of decreased circulatory flow related to slowed heart rate and reduced gill surface area (McKim, 1987b).
Evidence Supporting this KER
Dysregulation of heart rate and vascular tone manifests in the form of reduced gill surface area, reduced fluid flow through the gills and reduced circulatory flow. These factors contribute to a reduction in the available oxygen, so it is biologically plausible that these factors cause respiratory distress in fish (Duangsawasdi, 1977).
Data collected in experimental studies in Rainbow Trout found that AChE inhibition decreased heart rate and increased ventilation volume. However, in spite of the increase in ventilation volume, oxygen utilization remained low. Therefore, it is biologically plausible that reduced fluid flow through the gills leads to respiratory distress in fish (Duangsawasdi, 1977).
Acephate and fenitrothion exposure in adult rainbow trout resulted in decreased heart rate, increased ventilation rate and amplitude similarly characteristic to fish exposed to hypoxia. ECG after exposure showed irregular heart beats and changes in ECG waveforms (Duagsawasdi 1978, Duagsawasdi and Klaverkamp, 1979).
Uncertainties and Inconsistencies
The relationship between dysregulation of heart rate and vascular tone and respiratory distress/arrest could be bidirectional because many fish studies have shown that hypoxia leads to bradycardia (Farrell, 2007).
Quantitative Understanding of the Linkage
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
The relationship between dysregulated heart rate and vascular tone leading to respiratory distress/arrest has been proposed in Rainbow Trout (McKim, 1987, Duangsawasdi, M., 1977, Duangsawasdi, M and Klaverkamp, JF, 1979).
Duangsawasdi M. 1977. Organophosphate insecticide toxicity in rainbow trout (Salmo gairdneri). Effects of temperature and investigations on the sites of action. PhD thesis. University of Manitoba, Manitoba, Canada.
Duangsawasdi M, Klaverkamp JF. 1979. Acephate and fenitrothion toxicity in rainbow trout: Effects of temperature stress and investigations on the sites of action. In Aquatic Toxicology, Vol 2, STP 667. ASTM International, Philadelphia, PA, USA, pp 35–51.
McKim, J.M., Schmieder, P.K., Niemi, G.J., Carlson, R.W., Henry, T.R. 1987. Use of respiratory‐cardiovascular responses of rainbow trout (Salmo gairdneri) in identifying acute toxicity syndromes in fish: Part 2. Malathion, carbaryl, acrolein, and benzaldehyde. Environ Toxicol Chem 6:313–328.
Farrell, AP. Tribute to P. L. Lutz: a message from the heart – why hypoxic bradycardia in fishes? Journal of Experimental Biology 2007 210: 1715-1725