Low-Energy Shockwave Treatment Distal To Peripheral Vascular Disease

Project: Research project

Description

Peripheral vascular disease (PVD) is becoming increasingly common in the aging population of the Western
world. Renovascular hypertension (RVH) associated with large vessel PVD induces remodeling and loss of
downstream microvessels (MV), which are often irreversible after restoration of vascular patency. Alas,
adequate strategies to restore the microcirculation and improve outcomes in RVH and PVD are yet to be
identified and remain in dire need.
Non-invasive low-energy extracorporeal shock wave treatment (SWT) is a novel experimental strategy, which
generates mechanical forces that exert localized stress on cell membranes and elicit biological responses in
the cardiovascular and musculoskeletal systems, including suppression of inflammation and stimulation of new
MV formation. Remarkably, the potential of this novel approach to protect the microcirculation in chronic RVH
and increase MV viability has not been explored.
We have developed and characterized novel swine models of RVH that closely mimic human pathophysiology.
Furthermore, we have developed and refined unique imaging techniques ideally suited for probing MV adaptive
processes in PVD, as well as their potential contribution to MV injury and viability. These tools now provide a
unique opportunity to assess the effects of low-energy extracorporeal SWT on pathophysiology and outcomes
in RVH, and the feasibility of modifying them with novel interventions.
The working hypothesis underlying this proposal is that SWT in RVH-PVD is safe, and would decrease MV
injury, improve function and oxygenation, and thereby improve recovery upon restoration of upstream
vascular patency. To test this hypothesis, we will study the effects of SWT utilizing a combination of cutting-
edge multi-detector CT (MDCT), magnetic resonance imaging (MRI), and micro-CT using innovative tools.
Furthermore, the ability of SWT to improve renal recovery prospects will be tested in PVD pigs undergoing
revascularization and stenting.
Two specific aims will be pursued: Specific Aim 1 will test the hypothesis that SWT is safe, and would improve
function and structure distal to vascular obstruction 4 weeks later. Specific Aim 2 will test the hypothesis that
SWT would restore the recovery potential of the kidney in response to revascularization of PVD.
The proposed studies will advance our understanding of the pathogenesis of MV injury distal to PVD, and may
establish a novel, clinically feasible therapeutic strategy. Improvement of the MV network is a promising
technique in cardiovascular medicine, but this cutting edge approach is yet to be applied in RVH-PVD. Thus,
these studies will likely contribute significantly towards management of PVD.
StatusFinished
Effective start/end date1/1/1412/31/16

Funding

  • National Institutes of Health: $195,769.00
  • National Institutes of Health: $238,500.00

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Peripheral Vascular Diseases
Renovascular Hypertension
Microvessels
Vascular Patency
Microcirculation
Swine
Wounds and Injuries
Kidney
Musculoskeletal System
Cardiovascular System
Blood Vessels
Magnetic Resonance Imaging
Cell Membrane
Medicine
Inflammation
Western World

ASJC

  • Medicine(all)