Augmentation of Tissue Perfusion in Patients With Peripheral Artery Disease Using Microbubble Cavitation.
Aged
Animals
Blood Flow Velocity
Contrast Media
/ administration & dosage
Disease Models, Animal
Female
Hindlimb
Humans
Injections, Intravenous
Leg
Male
Mice
Mice, Inbred C57BL
Microbubbles
Middle Aged
Muscle, Skeletal
/ blood supply
Peripheral Arterial Disease
/ diagnostic imaging
Regional Blood Flow
Treatment Outcome
Ultrasonic Therapy
cavitation
microcirculation
muscle perfusion
peripheral artery disease
ultrasound
Journal
JACC. Cardiovascular imaging
ISSN: 1876-7591
Titre abrégé: JACC Cardiovasc Imaging
Pays: United States
ID NLM: 101467978
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
01
03
2019
revised:
20
05
2019
accepted:
06
06
2019
pubmed:
20
8
2019
medline:
11
11
2020
entrez:
19
8
2019
Statut:
ppublish
Résumé
The authors investigated ideal acoustic conditions on a clinical scanner custom-programmed for ultrasound (US) cavitation-mediated flow augmentation in preclinical models. We then applied these conditions in a first-in-human study to test the hypothesis that contrast US can increase limb perfusion in normal subjects and patients with peripheral artery disease (PAD). US-induced cavitation of microbubble contrast agents augments tissue perfusion by convective shear and secondary purinergic signaling that mediates release of endogenous vasodilators. In mice, unilateral exposure of the proximal hindlimb to therapeutic US (1.3 MHz, mechanical index 1.3) was performed for 10 min after intravenous injection of lipid microbubbles. US varied according to line density (17, 37, 65 lines) and pulse duration. Microvascular perfusion was evaluated by US perfusion imaging, and in vivo adenosine triphosphate (ATP) release was assessed using in vivo optical imaging. Optimal parameters were then used in healthy volunteers and patients with PAD where calf US alone or in combination with intravenous microbubble contrast infusion was performed for 10 min. In mice, flow was augmented in the US-exposed limb for all acoustic conditions. Only at the lowest line density was there a stepwise increase in perfusion for longer (40-cycle) versus shorter (5-cycle) pulse duration. For higher line densities, blood flow consistently increased by 3-fold to 4-fold in the US-exposed limb irrespective of pulse duration. High line density and long pulse duration resulted in the greatest release of ATP in the cavitation zone. Application of these optimized conditions in humans together with intravenous contrast increased calf muscle blood flow by >2-fold in both healthy subjects and patients with PAD, whereas US alone had no effect. US of microbubbles when using optimized acoustic environments can increase perfusion in limb skeletal muscle, raising the possibility of a therapy for patients with PAD. (Augmentation of Limb Perfusion With Contrast Ultrasound; NCT03195556).
Sections du résumé
OBJECTIVES
The authors investigated ideal acoustic conditions on a clinical scanner custom-programmed for ultrasound (US) cavitation-mediated flow augmentation in preclinical models. We then applied these conditions in a first-in-human study to test the hypothesis that contrast US can increase limb perfusion in normal subjects and patients with peripheral artery disease (PAD).
BACKGROUND
US-induced cavitation of microbubble contrast agents augments tissue perfusion by convective shear and secondary purinergic signaling that mediates release of endogenous vasodilators.
METHODS
In mice, unilateral exposure of the proximal hindlimb to therapeutic US (1.3 MHz, mechanical index 1.3) was performed for 10 min after intravenous injection of lipid microbubbles. US varied according to line density (17, 37, 65 lines) and pulse duration. Microvascular perfusion was evaluated by US perfusion imaging, and in vivo adenosine triphosphate (ATP) release was assessed using in vivo optical imaging. Optimal parameters were then used in healthy volunteers and patients with PAD where calf US alone or in combination with intravenous microbubble contrast infusion was performed for 10 min.
RESULTS
In mice, flow was augmented in the US-exposed limb for all acoustic conditions. Only at the lowest line density was there a stepwise increase in perfusion for longer (40-cycle) versus shorter (5-cycle) pulse duration. For higher line densities, blood flow consistently increased by 3-fold to 4-fold in the US-exposed limb irrespective of pulse duration. High line density and long pulse duration resulted in the greatest release of ATP in the cavitation zone. Application of these optimized conditions in humans together with intravenous contrast increased calf muscle blood flow by >2-fold in both healthy subjects and patients with PAD, whereas US alone had no effect.
CONCLUSIONS
US of microbubbles when using optimized acoustic environments can increase perfusion in limb skeletal muscle, raising the possibility of a therapy for patients with PAD. (Augmentation of Limb Perfusion With Contrast Ultrasound; NCT03195556).
Identifiants
pubmed: 31422129
pii: S1936-878X(19)30588-1
doi: 10.1016/j.jcmg.2019.06.012
pmc: PMC7018586
mid: NIHMS1534593
pii:
doi:
Substances chimiques
Contrast Media
0
Banques de données
ClinicalTrials.gov
['NCT03195556']
Types de publication
Clinical Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
641-651Subventions
Organisme : NIH HHS
ID : P51 OD011092
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL078610
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL130046
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL094294
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Références
Circulation. 2009 Mar 17;119(10):1378-85
pubmed: 19255341
Circ Cardiovasc Imaging. 2015 Apr;8(4):
pubmed: 25834183
Circulation. 2017 Mar 28;135(13):1240-1252
pubmed: 28174191
Thromb Haemost. 2015 Jun;113(6):1357-69
pubmed: 25809056
Am J Physiol Heart Circ Physiol. 2001 Dec;281(6):H2432-40
pubmed: 11709409
Thromb Haemost. 2002 Nov;88(5):865-70
pubmed: 12428107
J Am Soc Echocardiogr. 2011 Dec;24(12):1400-8
pubmed: 22037348
Ultrasound Med Biol. 2015 Feb;41(2):456-64
pubmed: 25542487
Ultrasound Med Biol. 2003 May;29(5):739-48
pubmed: 12754073
Ultrasound Med Biol. 2016 Jul;42(7):1531-40
pubmed: 27083977
J Am Coll Cardiol. 2006 Aug 1;48(3):532-7
pubmed: 16875980
Microcirculation. 2013 Apr;20(3):239-47
pubmed: 23311975
Circulation. 1998 Feb 10;97(5):473-83
pubmed: 9490243
Circ Cardiovasc Imaging. 2015 Apr;8(4):
pubmed: 25855669
J Am Coll Cardiol. 2016 May 31;67(21):2506-15
pubmed: 27230046
Cardiovasc Res. 2017 Apr 1;113(5):508-518
pubmed: 28158679