Comparison of Atlanto-axial Artery Hemodynamics During Functional Positioning Tests with Doppler Ultasound in Rhesus Macaques

摘要

Background: Cervical Spondylotic Arteriopathy (CSA) is a commoncondition that causes of chronic complaint among middle-aged and elderlypeople.One possible etiology is that of head movements inducingintermittent arterial vasospasm and decreased blood flow in thevertebrobasilar systems.Clinical symptoms mainly are dizziness, syncope,blurring of vision and tinnitus without any specific characterization of CSAitself, as these general symptoms can result from a lot of diseases.It isdifficult to make an exact diagnosis based on clinical symptoms alone.Inthe hospital setting, Doppler ultrasound and functional positioning tests ofthe cervical spine are commonly used to identify the presence of CSA;
　　however, ultrasound studies have failed to indicate a consistent movementthat could be considered sensitive and specific in diagnosis of thiscondition.Upon reviewing, no relevant studies have evaluated blood flowthroughout a sequence of functional positioning tests to determine if bloodflow changes reflect that the artery is being progressively stressed.
　　With all these studies, clinical data derived from human trials areusually complicated by research ethics and uncontrolled variables, and aredifficult to interpret.Due to their genetic and genomic similarity, anatomicand physiologic closeness to humans, it is well known that the rhesusmacaque (Macaca mulatta) offers the optimal model for the medical andbiological research on human health-related topics.It is necessary toreplicate functional positioning tests in human clinical trials on rhesusmonkeys, and refine clinical reasoning based on direct blood flow velocitydata across a range of mechanical challenges to the VA of rhesus monkeys.
　　Objective: With the use of duplex Doppler ultrasound (US), to obtainbase-line data for VA blood flow at the atlanto-axial joint, and to detect ifend of range cervical spine movement produces measurable and significantchanges in VA blood flow in healthy rhesus monkeys; with the applicationof CT angiography (CTA), to have an insight into the cervical spine andcervical vasculature of rhesus monkey in its comparability to humans, andto open the possibility of model human disease such as CSA relatedvertebrobasilar ischemia in rhesus monkeys; to provide some evidence onwhich to perform functional positioning tests in patient risk-assessment ofCSA related vertebrobasilar ischemia.
　　Materials and Methods: 6 adult rhesus macaques, 3 male, 3 female,approximate age 4.3±0.6 yrs.; weight 4.5±0.6 kg; height 51.5±2.1 cm(Macaca mulatta, Chongqing Medical University Animal Research Center,Chongqing, P.R.China) were involved in the current study.Five functionalpositioning test maneuvers (flexion 60°; extension 60°; rotation 90°;
　　extension 60°-rotation 90°; and extension 60°-rotation 90°-traction) wereperformed bilaterally with the rhesus monkey placed in supine position.Astandard, duplex Doppler ultrasound (Mylab50, Esaoto Corporation, Genoa,Italy) with a color flow mapping capability and a high frequency 12-5 MHzbroadband linear array transducer was used to measure the blood flowvelocities including peak systolic velocity (PSV, cm/s) and end diastolicvelocity (EDV, cm/s), resistance index (RI) and lumen diameter (LD, cm)in each of the positions three time for both left and right VA.The AquilionONE 320-slice CT scanner and VitreaFx Workstation with 4D imagingsoftware (Aquilion One, Toshiba, Japan) were used to perform andreconstruct CTA scans of one rhesus monkey at the head and neck regionfor revealing any resemblance between the cervical spine of humans andrhesus monkeys.The mean (± SD) blood flow PSVs and EDVs, RIs, andLDs of all 6 rhesus monkeys were calculated for the left and right VA withthe cervical spine in each position.One-way ANOVA with repeatedmeasures were conducted to identify any statistically significant change (p＜ 0.05) between different cervical positions in each VA.Post hoc tests werecalculated with Bonferroni correction for multiple comparisons (p ＜ 0.05).
　　Results: The blood flow PSV is significantly reduced by movementsinvolving contralateral rotation (p ＜ 0.05), extension with ipsilateral andcontralateral rotation (p ＜ 0.001); the application of unilateral traction atC1-C2 segment produced the maximal mechanical stress to the artery (p ＜
　　0.001).The mean EDV of left and right VAs also decreased significantlyduring contralateral rotation (p ＜ 0.05), extension with ipsilateral andcontralateral rotation (p ＜ 0.05), and the additional traction force (p ＜ 0.001)as compared with the neutral position.A significant increase in RIs withleft rotation (p ＜ 0.05) and extension-left rotation-traction (p =0.003) wasdemonstrated in right VAs.For the left VA there were similar changes in theRIs, but were not significant.Mean LD of VA in the neutral position wasfound approximately 1.0 mm on both sides and no significant differenceswas indicated within subjects and during the test sequence.
　　CTA results indicated that the cervical spine of rhesus monkey areanatomically similar to the human.Comparison of the different VA regions,such as the intravertebral and atlanto-axial segments, indicated that theanatomy of bony structure and the pattern of vessel distribution weresimilar in rhesus monkeys and humans.
　　Conclusion: On the basis of the reference data presented in this study,the atlanto-axial segment of the VA is subjected to forces that are sufficientto reduce blood flow velocity in positions such as contralateral rotation,extension with ipsilateral and contralateral rotations; combined extension-rotation with traction of the cervical spine have a particularly significanteffect in reducing maximum blood flow in the contralateral VA; similaritiesbetween rhesus monkeys and humans in cervical spine structures open thepossibility to model CSA related vertebrobasilar ischemia in rhesusmonkeys and to yield insights into appropriate conclusions; the preliminaryevidence regarding the hemodynamic responses of VA in rhesus monkeysare of value to serving as a reference for performing functional positioningtests in humans and for allowing more accurate interpretation of humandata.

目录

声明

CONTENT

LIST OF ABBREVIATIONS

ABSTRACT

INTRODUCTION

1 Pathogenesis

2 Diagnosis

3 Controversy in Current Research

MATERIALS AND METHODS

1 Subjects

2 Equipments

2．1 Ultrasonography

2．2 CT-Angiography

3 Functional Positioning Test Maneuvers

3．1 Flexion 60°

3．2 Extension 60°

3．3 Rotation 90°

3．4 Extension 60° and Rotation 90°

3．5 Extension 60°，Rotation 90° and Traction

4 Ultrasonographic Examination

5 CT-Angiography Examination

6 Statistical Analysis

RESULTS

1 Ultrasonographic Findings

1．1 Comparison of VA Blood Flow in Various Cervical Positions

1．2 Comparison of VA Blood Flow between Left and Right VAs

1．3 Doppler Waveforms of Blood Flow

2 CT-Angiography Findings

DISCUSSION

1 Interpretation of Results

2 Rhesus Macaques in Comparison with Humans

3 Limitations of the Study

4 Implications for Future Study and Clinical Practice

CONCLUSION

REFERENCE

APPENDIX

ARTICLE REVIEW

ACKNOWLEDGEMENT

AWARD AND PUBLICATION