The impact of collateral therapeutics on stroke hemodynamics in normotensive and hypertensive rats: a step toward translation
IntroductionStroke interventions that increase collateral flow have the potential to salvage penumbral tissue and increase the number of patients eligible for reperfusion therapy. We compared the efficacy of two different collateral therapeutics during transient middle cerebral artery occlusion (tMC...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-03-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1373445/full |
| _version_ | 1827312432538714112 |
|---|---|
| author | Marilyn J. Cipolla Marilyn J. Cipolla Marilyn J. Cipolla Marilyn J. Cipolla Ryan D. Hunt David S. Liebeskind Sarah M. Tremble |
| author_facet | Marilyn J. Cipolla Marilyn J. Cipolla Marilyn J. Cipolla Marilyn J. Cipolla Ryan D. Hunt David S. Liebeskind Sarah M. Tremble |
| author_sort | Marilyn J. Cipolla |
| collection | DOAJ |
| description | IntroductionStroke interventions that increase collateral flow have the potential to salvage penumbral tissue and increase the number of patients eligible for reperfusion therapy. We compared the efficacy of two different collateral therapeutics during transient middle cerebral artery occlusion (tMCAO) in normotensive and hypertensive rats.MethodsThe change in collateral and core perfusion was measured using dual laser Doppler in response to either a pressor agent (phenylephrine, 10 mg/kg iv or vehicle) or a collateral vasodilator (TM5441, 5 mg/kg iv or vehicle) given 30 min into tMCAO in male Wistar and spontaneously hypertensive rats (SHRs).ResultsPressor therapy increased collateral flow in the Wistar rats but was ineffective in the SHRs. The increase in collateral flow in the Wistar rats was associated with impaired cerebral blood flow autoregulation (CBFAR) that was intact in the SHRs. TM5441 caused a decrease in collateral perfusion in the Wistar rats and a modest increase in the SHRs. The pressor therapy reduced early infarction in both groups but increased edema in the SHRs, whereas TM5441 did not have any beneficial effects in either group.ConclusionsThus, the pressor therapy was superior to a collateral vasodilator in increasing collateral flow and improving outcomes in the Wistar rats, likely due to pial collaterals that were pressure passive; the lack of CBF response in the SHRs to pressor therapy was likely due to intact CBFAR that limited perfusion. While TM5441 modestly increased CBF in the SHRs but not in the Wistar rats, it did not have a beneficial effect on stroke outcomes. These results suggest that collateral therapies may need to be selected for certain comorbidities. |
| first_indexed | 2024-04-24T21:43:16Z |
| format | Article |
| id | doaj.art-0d40aca288d246ac9af98287683f2d11 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-24T21:43:16Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-0d40aca288d246ac9af98287683f2d112024-03-21T04:37:11ZengFrontiers Media S.A.Frontiers in Neurology1664-22952024-03-011510.3389/fneur.2024.13734451373445The impact of collateral therapeutics on stroke hemodynamics in normotensive and hypertensive rats: a step toward translationMarilyn J. Cipolla0Marilyn J. Cipolla1Marilyn J. Cipolla2Marilyn J. Cipolla3Ryan D. Hunt4David S. Liebeskind5Sarah M. Tremble6Department of Neurological Sciences, Larner College of Medicine, University of Vermont, Burlington, VT, United StatesDepartment of Obstetrics, Gynecology and Reproductive Sciences, Larner College of Medicine, University of Vermont, Burlington, VT, United StatesDepartment of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT, United StatesDepartment of Electrical and Biomedical Engineering, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT, United StatesDepartment of Neurological Sciences, Larner College of Medicine, University of Vermont, Burlington, VT, United StatesDepartment of Neurology, University of California Los Angeles, Los Angeles, CA, United StatesDepartment of Neurological Sciences, Larner College of Medicine, University of Vermont, Burlington, VT, United StatesIntroductionStroke interventions that increase collateral flow have the potential to salvage penumbral tissue and increase the number of patients eligible for reperfusion therapy. We compared the efficacy of two different collateral therapeutics during transient middle cerebral artery occlusion (tMCAO) in normotensive and hypertensive rats.MethodsThe change in collateral and core perfusion was measured using dual laser Doppler in response to either a pressor agent (phenylephrine, 10 mg/kg iv or vehicle) or a collateral vasodilator (TM5441, 5 mg/kg iv or vehicle) given 30 min into tMCAO in male Wistar and spontaneously hypertensive rats (SHRs).ResultsPressor therapy increased collateral flow in the Wistar rats but was ineffective in the SHRs. The increase in collateral flow in the Wistar rats was associated with impaired cerebral blood flow autoregulation (CBFAR) that was intact in the SHRs. TM5441 caused a decrease in collateral perfusion in the Wistar rats and a modest increase in the SHRs. The pressor therapy reduced early infarction in both groups but increased edema in the SHRs, whereas TM5441 did not have any beneficial effects in either group.ConclusionsThus, the pressor therapy was superior to a collateral vasodilator in increasing collateral flow and improving outcomes in the Wistar rats, likely due to pial collaterals that were pressure passive; the lack of CBF response in the SHRs to pressor therapy was likely due to intact CBFAR that limited perfusion. While TM5441 modestly increased CBF in the SHRs but not in the Wistar rats, it did not have a beneficial effect on stroke outcomes. These results suggest that collateral therapies may need to be selected for certain comorbidities.https://www.frontiersin.org/articles/10.3389/fneur.2024.1373445/fullischemic strokecollateral circulationhypertensiontreatmentautoregulation |
| spellingShingle | Marilyn J. Cipolla Marilyn J. Cipolla Marilyn J. Cipolla Marilyn J. Cipolla Ryan D. Hunt David S. Liebeskind Sarah M. Tremble The impact of collateral therapeutics on stroke hemodynamics in normotensive and hypertensive rats: a step toward translation Frontiers in Neurology ischemic stroke collateral circulation hypertension treatment autoregulation |
| title | The impact of collateral therapeutics on stroke hemodynamics in normotensive and hypertensive rats: a step toward translation |
| title_full | The impact of collateral therapeutics on stroke hemodynamics in normotensive and hypertensive rats: a step toward translation |
| title_fullStr | The impact of collateral therapeutics on stroke hemodynamics in normotensive and hypertensive rats: a step toward translation |
| title_full_unstemmed | The impact of collateral therapeutics on stroke hemodynamics in normotensive and hypertensive rats: a step toward translation |
| title_short | The impact of collateral therapeutics on stroke hemodynamics in normotensive and hypertensive rats: a step toward translation |
| title_sort | impact of collateral therapeutics on stroke hemodynamics in normotensive and hypertensive rats a step toward translation |
| topic | ischemic stroke collateral circulation hypertension treatment autoregulation |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1373445/full |
| work_keys_str_mv | AT marilynjcipolla theimpactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT marilynjcipolla theimpactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT marilynjcipolla theimpactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT marilynjcipolla theimpactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT ryandhunt theimpactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT davidsliebeskind theimpactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT sarahmtremble theimpactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT marilynjcipolla impactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT marilynjcipolla impactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT marilynjcipolla impactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT marilynjcipolla impactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT ryandhunt impactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT davidsliebeskind impactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation AT sarahmtremble impactofcollateraltherapeuticsonstrokehemodynamicsinnormotensiveandhypertensiveratsasteptowardtranslation |