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Event: 1703

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Dysregulation of heart rate and vascular tone

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Cardiovascular dysregulation

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Biological Context

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Level of Biological Organization
Organ

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
AChE inhibition - acute mortality	KeyEvent	Cataia Ives (send email)	Under Development: Contributions and Comments Welcome	Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Heart rate and vascular function are sensitive to increases in cholinergic signalling. While specific cellular-molecular signalling pathways direct cardiovascular responses in a specific direction, acetylcholine acts at multiple cardiovascular regulatory input points such that the sum impact is best described as a dysregulation event.
In response to elevated levels of acetylcholine, muscarinic M2 receptors are hyperactivated to slow heart rate and induce hypotension. In contrast, nicotinic receptors respond to increased acetylcholine by increasing heart rate (tachycardia) and producing hypertension. The timing of how these contrasting inputs are integrated is complex (Campen, Lodish)

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

The methods used to detect and measure dysregulation of heart rate and vascular tone vary depending on the taxa and life stage. In some cases, special apparatuses are needed to stabilize an animal, in order to collect cardiovascular measurements.

Humans

In human patient cohort studies, cardiovascular status is determined from various measurements collected in medical settings: pulse rate, blood pressure and ECG recordings (Peter, Karki).

Rodents

In experimental settings, blood pressure and pulse rate measurements in rats have been collected using a pressure transducer (Utah Medical, Midvale UT) connected to polyethylene tubing. Pulse rate was calculated using peak systolic blood pressure of the arterial pressure tracing as the marker for a single heartbeat. The mean arterial pressure was calculated from the analogue signal (Gaspari, 2007).

Fish

Heart rate and vascular measurements can be collected from fish using various laboratory systems suited for the species size and life stage (for example, embryonic or adult).

Fish - heart rate in embryos

One study measured heart beats in embryos by direct observation of heartbeats observed under a dissecting microscope over 30 second time intervals (Steele, 2009)

Fish - cardiovascular dynamics in adults

Collection of heart rate and vascular measurements in fish can require that the fish is hooked up to special respirometer-metabolism chambers (McKim, 1982). Individuals were anesthetized with 100 mg/L MS-222 (tricaine methanesulfonate) and immobilized by spinal transection. Coated 30 gauge copper wire electrodes were implanted to collect electrocardiography (ECG) and heart rate (HR) measurements. ECG and HR measurements were collected every 2 hours during a 24-48 hour time period. Blood pressure was monitored with an indwelling dorsal aortic cannula that was filled with heparinized saline and attached to a pressure transducer (Statham Model No. P23Db; Could Inc., Medical Products Division, Oxnard, CA). The pressure transducer was manometrically calibrated with a water column to read in millimeters of mercury. The pressure transducer and electrodes were connected to a Beckman dynograph recorder (Beckman Instrument Co., Skokie, IL) (McKim, 1987).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Cardiovascular dysregulation has been observed in many taxa.

References

List of the literature that was cited for this KE description. More help

Steele SL, Lo KH, Li VW, Cheng SH, Ekker M, Perry SF. 10.1152/ajpregu.00036.2009. Epub 2009 Jun 10. Loss of M2 muscarinic receptor function inhibits development of hypoxic bradycardia and alters cardiac beta-adrenergic sensitivity in larval zebrafish (Danio rerio). Am J Physiol Regul Integr Comp Physiol. 2009 Aug;297(2)
Gaspari RJ, Paydarfar D. Pathophysiology of respiratory failure following acute dichlorvos poisoning in a rodent model. Neurotoxicology. 2007 May;28(3):664-71.
Campen. Toxic Responses of the Heart and Vascular System. In Casarett and Doull's Toxicology: The Basic Science of Poisons. 9th ed. 999-952.
Karki P, Ansari JA, Bhandary S, Koirala S. Cardiac and electrocardiographical manifestations of acute organophosphate poisoning. Singapore Med J. 2004;45:385–9.
Lodish, Harvey, Arnold Berk, S. Lawrence Zipursky, Paul Matsudaira, David Baltimore, and James Darnell. 2000. “Neurotransmitters, Synapses, and Impulse Transmission.” Molecular Cell Biology. 4th Edition. https://www.ncbi.nlm.nih.gov/books/NBK21521/.
McKim, JM, Goeden, HM. A direct measure of the uptake efficiency of a xenobiotic chemical across the gills of brook trout (Salvelinus fontinalis) under normoxic and hypoxic conditions, Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, Volume 72, Issue 1, 1982, pgs 65-74
McKim, James M., Patricia K. Schmieder, Richard W. Carlson, Evelyn P. Hunt, and Gerald J. Niemi. 1987. “Use of Respiratory-Cardiovascular Responses of Rainbow Trout (Salmo Gairdneri) in Identifying Acute Toxicity Syndromes in Fish: Part 1. Pentachlorophenol, 2,4-Dinitrophenol, Tricaine Methanesulfonate and 1-Octanol.” Environmental Toxicology and Chemistry 6 (4): 295–312. https://doi.org/10.1002/etc.5620060407.
Peter, J.V., Sudarsan, T.I. and Moran, J.L. 2014. vas. Indian J Crit Care Med. 18(11): 735–745.