Shockwave Lithotripsy Program Project

Indianapolis-Project 1 (click for Indianapolis Project 2)

Program Project Leader: Andrew Evan, IUSM, Dept. of Anatomy MS 5055, 635 Barnhill Drive, Indianapolis, IN 46202 <evan@anatomy.iupui.edu>
317 274 8102 fax: 317 278 2040
 
Rajiv Agarwal MD, Nephrology Dept. VA A754 , 1481 W. 10th St. Indianapolis IN 46202
<ragarwal@iupui.edu
317 554 0000 x2241
 
Philip M.Blomgren IUSM, Dept. of Anatomy MS 5055, 635 Barnhill Drive, Indianapolis, IN 46202
<blomgren@anatomy.iupui.edu>
317 278 1792 fax:317 278 2040
 
Bret A.Connors, Ph.D. IUSM Dept. of Anatomy MS 5055, 635 Barnhill Drive, Indianapolis, IN 46202
<connors@anatomy.iupui.edu>
317 274 3494 fax: 317 278 2040
 
Jeremy Doherty, Dept of Pharm. IUSM MS A504, 635 Barnhill Drive, Indianapolis, IN 46202
<doherty@anatomy.iupui.edu>
317 274 1558, 317 274 7714
 
Naomi S. Fineberg Ph.D. Krannert Inst. of Cardiology, Indiana University School of Medicine, 1111 W. 10th Street, Indianapolis, IN 46202 5120
<fineberg@kimail.dmed.iupui.edu>
317 630 6329
 
James E. Lingeman MD, Methodist Hospital of Indiana, 1801 North Senate Boulevard Suite 655, Indianapolis, IN 46202
<jlingeman@clarian.com
317 929 1124 FAX: 317 924 7791
 
Jeff Moody MD, Methodist Hospital of Indiana, 1801 North Senate Blvd. suite 655, Indianapolis IN 46202
<jmoody2@iupui.edu>
317 929 1124 FAX: 317 924 7791
 
Chee Saw, Methodist Hospital of Indiana, 1801 N. Senate Blvd. Suite 655, Indianapolis IN 46202
<csaw@clarian.com>
317 929 1124 FAX: 317 924 7791
 
Youzhi Shao, Dept. of Anatomy, IU Medical School MS 5065, 635 Barnhill Drive, Indianapolis, IN 46202
<shao@anatomy.iupui.edu>
317 274 3494
 
Anne Trout, Dept. of Medical Research Methodist Hosp. 1701 N Senate, Indianapolis, IN 46202
<atrout@clarian.com>
317 929 5402
 
Lynn R.Willis, Ph.D. IU Medical School, Dept. of Pharm. MS A528 635 Barnhill Drive, Indianapolis, IN 46202
<willisl@indycms.iupui.edu>
317 274 1562

Specific Aims of Project 1:

Aim 1: Define the relationship between lesion size induced by SWL and the subsequent impairment of renal hemodynamics and tubular function.

Hypothesis 1:: SWL-induced impairment of renal hemodynamics and tubular function increases with lesion size.

Hypothesis 2:: Systemic hemodynamic status alters the relationship between SWL-induced lesion size and renal functional impairment.

Hypothesis 1 seeks to confirm our suspicion that lesion size correlates better with tubular impairment than with decreased RBF. Hypothesis 2 aims at defining the role of intrarenal hemorrhage and elevated blood pressure as risk factors for SWL-induced injury, and whether by controlling them injury can be diminished or prevented. With Project 3, we use 3-D Color Power Angiography to measure blood flow.

Aim 2: Characterize the cellular, molecular and structural changes occurring in injured microvessels, tubules and interstitiial cells (immediately after SWL and for up to 3 months). Portions of this aim will be done in collaboration with Project 2.

Hypothesis: The acute inflammation generated by shock wave-induced tissue injury promotes fibrogenesis leading to scar formation.

This hypothesis will determine if the acute injury triggers chronic complications. Studies to test the hypothesis will examine the progression of the SWL-induced lesion from several perspectives with Project 2.

Aim 3: Identify the factor(s) responsible for the bilateral reduction of RBF after SWL.

Hypothesis : The SWL-treated kidney produces one or more vasoactive substances, of humoral or neuronal origin, that reduce RBF.

This hypothesis assumes that SWL-induced renal vasoconstriction involves more than one mechanism and it focuses on several of the most likely possible mediators.

Aim 4: Determine the role of acoustic cavitation in SWL induced tissue injury.

Hypothesis: Acoustical cavitation is a major physical mechanism that induces tissue injury.

Newly developed techniques by project 3 of cavitation detection will be used in the auto-perfused porcine kidney.

Aim 5: Characterize the pressure wave at multiple sites within F2 using miniaturized transducer arrays attached to the kidney to deter-

mine the role of shear in tissue injury and develop a definition of "dose" for SWL (collaborative study with Projects 1, 3, 4 and Core B).

Hypothesis: SWL-induced changes in renal function and structure are induced by shear forces

New evidence from Project 4 suggests that non-cavitation shear forces are present at F2. SWL-induced renal injury may result from acoustical cavitation or shear forces. Studies to test this hypothesis aim at distinguishing between these physical forces.

Click to see some effects of SWL

Click to see kidney anatomy illustrations