1. This meta-analysis reviewed animal studies on functional vascular adaptation during pregnancy, focusing on vasodilator and vasoconstrictor responses in mesenteric arteries.
2. The analysis found uniformly upregulated flow-mediated vasodilation across species but heterogeneity in responses to pharmacological agents.
3. While most studies examined late pregnancy, the quality of evidence was limited due to a lack of randomization and blinding in the underlying studies.
4. Systematic reviews of animal data can provide new insights, identify gaps, and increase the efficacy of animal research compared to individual studies.
2. Insight in:
1. Cellular pathways involved in pregnancy-induced
vasodilation
2. Systematic overview of literature (mesenteric arteries)
3. Advantages of systematic review of animal studies
3. During pregnancy
Human Weeks of gestation
Rat NP 5 11 16 21 Days of gestation
Chamberlain and Broughton (1998); Slangen et al. (1996); Danielson et al. (1995)
11. Summary
• Pregnancy induces vasodilation
• Two types of stimuli (pharmacological / mechanical)
• G-protein coupled receptors are important
• Theories mainly based on rats
Mesenteric system is important
Conflicting results in literature
Idea
• Systematic review
Effect of first pregnancy on vascular responses in
mesenteric arteries
12. Goal
Selection of studies concerning
• Healthy subjects in their first pregnancy
• Healthy nulliparous subjects
• Comparable age
• Vasodilator and vasoconstrictor mesenteric responses
13. Pubmed and Embase search
Three components
1. Pregnancy
2. Mesenteric arteries
3. Vasodilator and vasoconstrictor responses
14. Component Description
Pregnancy "pregnancy"[MeSH Terms] OR "pregnancy"[tiab] OR "pregnancies"[tiab] OR
"gestation"[tiab] OR "pregnant"[tiab] OR "maternal-fetal relations"[tiab]
Mesenteric arteries "mesenteric arteries"[MeSH Terms] OR "Mesentery/blood supply"[Mesh] OR
"mesenteric"[tiab] OR "mesentery artery"[tiab] OR "mesentery arteries"[tiab] OR
"mesenterial artery"[tiab] OR "mesenterial arteries"[tiab] OR "arteria
mesenterica"[tiab] OR "omental microvessels"[tiab] OR "omental arteries"[tiab] OR
"omental artery"[tiab]
Vasoconstrictor and "vasoconstriction"[MeSH Terms] OR "vasoconstriction"[tiab] OR
vasodilator responses "vasoconstrictions"[tiab] OR "vasoconstrictor agents"[MeSH Terms] OR
"vasoconstrictor agents"[Pharmacological Action] OR "vascular resistance"[MeSH
Terms] OR "vascular resistance"[tiab] OR "vascular capacitance"[MeSH Terms] OR
("vascular"[tiab] AND "capacitance"[tiab]) OR "vasoconstrictor"[tiab] OR
"vasoconstrictors"[tiab] OR "vasopressor"[tiab] OR "vasoactive agonist"[tiab] OR
"vasoactive agonists"[tiab] OR "vasopressors"[tiab] OR "vasomotor system"[MeSH
Terms] OR "vasomotor system"[tiab] OR "peripheral resistance"[tiab] OR "artery
constriction"[tiab] OR "vessel constriction"[tiab] OR "vasoconstrictive"[tiab] OR
"vasoconstricting"[tiab] OR "vasoconstricted"[tiab] OR "vasodilation"[MeSH Terms]
OR "vasodilation"[tiab] OR "vasodilatation"[tiab] OR "vasodilatating"[tiab] OR
"vasodilating"[tiab] OR "vasodilative"[tiab] OR "vasodilatative"[tiab] OR "artery
dilation"[tiab] OR "vessel dilation"[tiab] OR "artery dilatation"[tiab] OR "vessel
dilatation"[tiab] OR "vasodilator agents"[MeSH Terms] OR "vasodilator
agents"[Pharmacological Action] OR "vasodilator"[tiab] OR "vasodilators"[tiab] OR
"vasorelaxation"[tiab] OR "Vascular Endothelium Dependent Relaxation"[tiab] OR
"Endothelium Dependent Relaxation"[tiab] OR "Vascular Endothelium-Dependent
Relaxation"[tiab] OR "Endothelium-Dependent-Relaxation"[tiab] OR
"hemodynamics"[MeSH Terms] OR "hemodynamics"[tiab]OR "hemodynamic"[tiab]
OR "vasodilated"[tiab] OR "vasoactive agent"[tiab] OR "vasoactive drug"[tiab] OR
"vasoactive drugs"[tiab] OR "dilation"[tiab] OR "dilatation"[tiab] OR
"contraction"[tiab] OR "relaxation"[tiab]
15. Inclusion and exclusion
Identified studies (n=398)
Title and abstract (n=302)
- No healthy first pregnancy versus virgin control (n=258)
- No mesenteric artery vasoconstrictor/vasodilator response (n=19)
- No standard medium (n=5)
- No original data; review (n=20)
Subtracted studies (n=96)
Full article (n=43)
- No healthy first pregnancy versus virgin control (n=12)
- No mesenteric artery vasoconstrictor/vasodilator response (n=26)
- No age-matching (n=5)
Included studies (n=55)
Responses (r=78)
- Response <5 measurements (r=38)
- Other blockade than NO, PGI2, endothelium (r=40)
Included responses (r=188)
- Pharmacological /
Electrical (r=160)
* EC50 described (r=83)
* Emax described (r=63)
* Graph present (r=130)
- Mechanical (r=28)
* Graph present (r=27)
16. Study characteristics
Species (55 studies)
• Rodents: - rat (n=46)
SDR (n=27)
WR (n=15)
unknown (n=1)
- mouse (n=5)
- guinea pig (n=2)
• Rabbit (n=1)
• Pigs (n=1)
Gestational period (188 responses)
• Early (r=3)
• Mid (r=23)
• Late (r=161)
• Unknown (r=1)
21. Conclusion
1. Most studies concern late pregnancy
2. Quality is limited
3. Flow-mediated vasodilation is uniformly upregulated
4. Heterogeneity amongst species
5. Importance of systematic reviews for animal data
6. Difficulty in extrapolation to vasodilator pathways
involved in human pregnancy
22. Take home message
Systematic reviews of animal studies
• Give new insight
• Identify lacunas in knowledge
• Lead to new original research
• Increase efficancy of animal use
• Reduce unnecessary use of animals
23. Take home message
Systematic review of animal studies
There is no excuse
24. Acknowledgements
Dr. CR Hooijmans
Dr. RBM de Vries
Drs. L. ten Bos
Prof. Dr. PABM Smits
Prof. Dr. FK Lotgering
Prof. Dr. MJ Ritskens
Prof. Dr. MEA Spaanderman