Rabbit Central Ear Artery Vasomotor Evaluation Method

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Solution Overview

Problem

Current methods for evaluating vasomotor responses in vivo lack sensitivity and dynamic range, failing to effectively assess the effects of test compounds on vasomotor function, particularly in the context of endothelial integrity and vasodilation mechanisms, which is crucial for understanding vascular diseases and drug interactions.

Innovation Solution

A method involving the administration of test compounds to rabbits, with measurements of the central ear artery lumen diameter using ultrasonic imaging, including pre-constriction with norepinephrine and subsequent vasodilation induced by acetylcholine, to assess the impact on vasomotor responses, allowing for the evaluation of both vasodilators and vasoconstrictors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current methods for evaluating vasomotor responses in vivo are used, then the evaluation can be performed, but the sensitivity and dynamic range are insufficient

Engineering Contradiction:
Improvesensitivity of vasomotor response evaluationVSAvoiddynamic range of evaluation
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent applies preliminary action by pre-constricting the central ear artery with norepinephrine before administering the test compound. This creates a baseline state of vasoconstriction that enhances the ability to detect subsequent vasodilatory responses, thereby improving sensitivity and dynamic range of the evaluation system.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent utilizes parameter changes by measuring variations in vessel lumen diameter in response to different pharmacological agents. By establishing a baseline diameter under controlled conditions and measuring changes after compound administration, the system achieves enhanced measurement precision and expanded dynamic range for evaluating vasomotor responses.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If the central ear artery lumen diameter is measured to evaluate vasomotor responses, then sensitivity and dynamic range are improved, but the complexity of the measurement system increases

Engineering Contradiction:
Improvesensitivity of vasomotor response evaluationVSAvoidcomplexity of ultrasonic imaging system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs copying by using ultrasonic imaging to create a visual representation (copy) of the central ear artery lumen. This allows non-invasive measurement of vessel diameter without requiring direct physical access or complex surgical instrumentation, thereby reducing overall system complexity while maintaining measurement precision.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent uses ultrasonic waves as an intermediary to measure vessel lumen diameter. The ultrasonic imaging system acts as a mediator between the researcher and the vascular structure, enabling precise measurements without direct contact or invasive procedures, thus simplifying the overall measurement system.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If pre-constriction with norepinephrine is performed before vasodilation assessment, then the dynamic range of measurement is enhanced, but the time required for the procedure increases

Engineering Contradiction:
Improvedynamic range of vasomotor evaluationVSAvoidtime for pre-constriction procedure
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by performing the norepinephrine pre-constriction step before the actual vasodilation assessment. This sequential approach ensures that the vessel is in a controlled constricted state ready for accurate measurement of vasodilatory responses, enhancing dynamic range while requiring minimal additional time through efficient protocol design.

Inventive Principle:
Principle #10Preliminary action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach provides a sensitive and dynamic method to evaluate vasomotor responses in vivo, enabling the assessment of drug effects on endothelial-dependent vasodilation and vasoconstriction, thereby aiding in the understanding of vascular diseases and the potential cardiovascular risks associated with drug treatments.

Implementation Method 1

The vasodilation is due to the stimulation of muscarinic M3 receptors by acetylcholine and other cholinomimetics on the endothelial cells and the subsequent release of the vasodilator nitric oxide (NO)

Methodology Applied
Scientific EffectNitric oxide release:

Implementation Method 2

the stimulation of muscarinic receptors in the smooth muscle cells in the presence of unopposed sympathetic adrenergic tone can not only result in loss of vasodilating response but potentially produce a vasoconstriction in blood vessels

Methodology Applied
Scientific EffectAdrenergic stimulation:

Implementation Method 3

measuring the lumen of the central ear artery of a rabbit

Methodology Applied
Scientific EffectUltrasonic imaging: Ultrasound

Data Source

PatentUS8852556B2Animal model for evaluating vasomotor response in vivo
Publication Date: 2014.10.07 JANSSEN RESEARCH & DEVELOPMENT LLC
  • US8852556B2 patent drawing
  • US8852556B2 patent drawing
  • US8852556B2 patent drawing

AI summary

A method for evaluating the effect of a compound on vasomotor response in vivo comprises the steps of administering said compound to a rabbit and measuring the diameter of the vessel lumen of a central ear artery of said rabbit in comparison with the baseline diameter of the vessel lumen of said central ear artery of said rabbit, said baseline diameter being measured prior to the administration of said compound.