Shock wave lithotripsy (SWL) produces a rapid inflammatory response in renal tissue. This study assessed the time course and location of the inflammatory response in our established porcine model of acute SWL-induced renal injury, using interleukin-6 (IL-6) as a marker of inflammation. The lower pole left renal calyx of anesthetized female pigs (30–35 lbs) received 2000 shock waves (SW) from a Dornier HM3 lithotripter (24 kV, 120 SW/min). Blood and urine samples were taken at timed intervals. At 4 hours post-treatment, kidneys were perfused with cold saline, excised, and tissue samples were flash-frozen in liquid N2. IL-6 was measured by ELISA (R&D Systems). IL-6 was not detectable in all blood, urine and renal tissue (cortex and medulla) samples from control animals (n=5). In SWL-treated animals (n=6), measurable levels of IL-6 were found in the SWL-treated lower pole medulla (18 ± 9 pg/mg protein, n=3). In contrast, blood, urine and other renal tissue (contralateral cortex and medulla; treated kidney: lower and upper pole cortex, upper pole medulla) samples from SWL-treated animals did not contain IL-6. In conclusion, while IL-6 is not a good blood or urinary marker for acute SWL-induced renal injury, elevated tissue levels of IL-6 following SWL appear to be highly localized to those medullary regions directly exposed to SWs, which are also sites of significant SWL-induced tissue trauma. Supported by NIH grant DK67133.

You have accessJournal of UrologyPodium, Wednesday, May 24, 2006, 1:00 - 3:00 pm1 Apr 20061668: Minimal Tissue Injury and Effective Stone Breakage in the Pig Model Using the Eisenmenger Broad Focal Zone, Low-Pressure Lithotripter Andrew P. Evan, Yura A. Pishchalnikov, James C. Williams, James A. McAteer, Bret A. Connors, Rajash K. Handa, Lynn R. Willis, Samuel C. Kim, and James E. Lingeman Andrew P. EvanAndrew P. Evan More articles by this author , Yura A. PishchalnikovYura A. Pishchalnikov More articles by this author , James C. WilliamsJames C. Williams More articles by this author , James A. McAteerJames A. McAteer More articles by this author , Bret A. ConnorsBret A. Connors More articles by this author , Rajash K. HandaRajash K. Handa More articles by this author , Lynn R. WillisLynn R. Willis More articles by this author , Samuel C. KimSamuel C. Kim More articles by this author , and James E. LingemanJames E. Lingeman More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)33860-6AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1668: Minimal Tissue Injury and Effective Stone Breakage in the Pig Model Using the Eisenmenger Broad Focal Zone, Low-Pressure Lithotripter." The Journal of Urology, 175(4S), p. 538 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4SApril 2006Page: 538 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Andrew P. Evan More articles by this author Yura A. Pishchalnikov More articles by this author James C. Williams More articles by this author James A. McAteer More articles by this author Bret A. Connors More articles by this author Rajash K. Handa More articles by this author Lynn R. Willis More articles by this author Samuel C. Kim More articles by this author James E. Lingeman More articles by this author Expand All Advertisement Loading ...

Lithotripsy shock waves (SW) to one renal pole damage that pole but protect the opposite pole from the damage inflicted by another, immediate application of SW. This study investigated whether the protection (1) occurs when the first treatment causes no injury, (2) is caused by SW or injury, (3) exhibits a threshold, and (4) occurs when the same pole receives both treatments. Six- to 7-wk-old anesthetized female pigs were studied. The following groups were studied: group 1 (n = 4), 2000 SW at 12 kV to one pole and 2000 SW at 24 kV (standard) to the opposite pole; group 2 (n = 6), same as group 1 except 500 12-kV SW pretreatment; group 3 (n = 8), 500 12-kV, 2000 standard SW, all to the same pole; and group 4 (n = 8), same as group 3 except 100 12-kV SW pretreatment. Mean +/- SD lesion size in group 1, first pole treated, was 0.66 +/- 0.82% of functional renal volume (FRV; P < 0.05 versus 5.22 +/- 3.6% FRV with no pretreatment [NP]; 95% confidence interval [CI] -7.0 to -2.1) and 0.50 +/- 0.68% FRV in the opposite pole after 2000 standard SW (P < 0.05 versus NP; 95% CI -9.4 to -0.08). Mean lesion size (first pole) in group 2 was 0.020 +/- 0.028% FRV (P < 0.01 versus NP; 95% Cl -9.2 to -1.2) and 0.43 +/- 0.54% FRV in the opposite pole after 2000 standard SW (P < 0.05 versus NP; 95% CI -8.8 to -0.82). Same-pole SW (groups 3 and 4) also protected. Mean lesion sizes were 0.28 +/- 0.33% (P < 0.01 versus NP; 95% Cl -8.0 to -1.9) in group 3 and 0.39 +/- 0.48% FRV (P < 0.01 versus NP; 95% CI -8.2 to -1.7) in group 4. It is concluded that the pretreatment protocol substantially limits the renal injury that normally is caused by SWL and occurs when the pretreatment and standard SW are applied to the same pole. The threshold for the protection may be < 100 SW.

You have accessJournal of UrologyPodium, Wednesday, May 24, 2006, 3:30 - 5:30 pm1 Apr 20061703: Demonstration of the Potential for Cavitation-Mediated Tissue Damage in Shock Wave Lithotripsy Brian R. Matlaga, Daniel L. Clark, Rajash K. Handa, Kelli R. Wind, Cynthia D. Johnson, Philip M. Blomgren, Bret A. Connors, Robin O. Cleveland, James A. McAteer, Andrew P. Evan, and Lynn R. Willis Brian R. MatlagaBrian R. Matlaga More articles by this author , Daniel L. ClarkDaniel L. Clark More articles by this author , Rajash K. HandaRajash K. Handa More articles by this author , Kelli R. WindKelli R. Wind More articles by this author , Cynthia D. JohnsonCynthia D. Johnson More articles by this author , Philip M. BlomgrenPhilip M. Blomgren More articles by this author , Bret A. ConnorsBret A. Connors More articles by this author , Robin O. ClevelandRobin O. Cleveland More articles by this author , James A. McAteerJames A. McAteer More articles by this author , Andrew P. EvanAndrew P. Evan More articles by this author , and Lynn R. WillisLynn R. Willis More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)33882-5AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1703: Demonstration of the Potential for Cavitation-Mediated Tissue Damage in Shock Wave Lithotripsy." The Journal of Urology, 175(4S), pp. 547–548 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4SApril 2006Page: 547-548 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Brian R. Matlaga More articles by this author Daniel L. Clark More articles by this author Rajash K. Handa More articles by this author Kelli R. Wind More articles by this author Cynthia D. Johnson More articles by this author Philip M. Blomgren More articles by this author Bret A. Connors More articles by this author Robin O. Cleveland More articles by this author James A. McAteer More articles by this author Andrew P. Evan More articles by this author Lynn R. Willis More articles by this author Expand All Advertisement PDF DownloadLoading ...

You have accessJournal of UrologyPodium, Wednesday, May 24, 2006, 3:30 - 5:30 pm1 Apr 20061721: The Effect of Shockwave Lithotripsy on Regional Renal Perfusion Brian R. Matlaga, Mark A. Green, Rajash K. Handa, Bret A. Connors, Andrew P. Evan, James E. Lingeman, and Lynn R. Willis Brian R. MatlagaBrian R. Matlaga More articles by this author , Mark A. GreenMark A. Green More articles by this author , Rajash K. HandaRajash K. Handa More articles by this author , Bret A. ConnorsBret A. Connors More articles by this author , Andrew P. EvanAndrew P. Evan More articles by this author , James E. LingemanJames E. Lingeman More articles by this author , and Lynn R. WillisLynn R. Willis More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)33900-4AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1721: The Effect of Shockwave Lithotripsy on Regional Renal Perfusion." The Journal of Urology, 175(4S), p. 553 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4SApril 2006Page: 553 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Brian R. Matlaga More articles by this author Mark A. Green More articles by this author Rajash K. Handa More articles by this author Bret A. Connors More articles by this author Andrew P. Evan More articles by this author James E. Lingeman More articles by this author Lynn R. Willis More articles by this author Expand All Advertisement PDF DownloadLoading ...

Background and Purpose: Shockwave lithotripsy (SWL) predictably damages renal tissue and transiently reduces function in both kidneys. This study characterized the effects on renal function of a supraclinical dose of shockwaves (SWs) (8000) in porcine kidneys and tested the hypothesis that such excessive treatment would intensify and prolong the resulting renal impairment.Materials and Methods: Pigs aged 6 to 7 weeks were anesthetized and assigned to one of three groups. Groups 1 (N = 8) and 2 (N = 6) each received 8000 SWs at 24 kV (Dornier HM3) to the lower-pole calix of one kidney. Group 3 (7 pigs) received sham treatment. Renal function was monitored for the first 4 hours after SW treatment in Group 1 and for 24 hours in Group 2. Plasma renin activity was measured in Groups 2 and 3.Results: The renal lesions produced by 8000 SWs comprised 13.8% +/- 1.4% of the renal mass. In the 4-hour protocol, this injury was associated with marked reduction of the glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary sodium excretion in both kidneys, although fractional sodium excretion was reduced only in the shocked kidneys. In the 24-hour protocol, GFR and RPF remained below baseline in shocked kidneys at 24 hours. Evidence of progressive ischemic injury was noted in shocked tissue at 24 hours after SW treatment.Conclusions: These findings support the hypothesis that the severity of the renal injury caused by SWL is related to the number of SWs administered and demonstrate the connection in this relation between renal structure and function.

You have accessJournal of UrologyPodium, Sunday, May 9, 2004, 3:30 - 5:30 pm1 Apr 2004704: Percutaneous Access Produces Prolonged Tubular Dysfunction in a Porcine Model Lynn R. Willis, Andrew P. Evan, Ryan F. Paterson, Ramsay L. Kuo, Samuel C. Kim, Bret A. Connors, Rajash K. Handa, and James E. Lingeman Lynn R. WillisLynn R. Willis More articles by this author , Andrew P. EvanAndrew P. Evan More articles by this author , Ryan F. PatersonRyan F. Paterson More articles by this author , Ramsay L. KuoRamsay L. Kuo More articles by this author , Samuel C. KimSamuel C. Kim More articles by this author , Bret A. ConnorsBret A. Connors More articles by this author , Rajash K. HandaRajash K. Handa More articles by this author , and James E. LingemanJames E. Lingeman More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)37953-9AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "704: Percutaneous Access Produces Prolonged Tubular Dysfunction in a Porcine Model." The Journal of Urology, 171(4S), p. 187 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 187 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Lynn R. Willis More articles by this author Andrew P. Evan More articles by this author Ryan F. Paterson More articles by this author Ramsay L. Kuo More articles by this author Samuel C. Kim More articles by this author Bret A. Connors More articles by this author Rajash K. Handa More articles by this author James E. Lingeman More articles by this author Expand All Advertisement PDF DownloadLoading ...

You have accessJournal of UrologyDiscussed Poster, Monday, May 10, 2004, 1:00 - 5:00 pm1 Apr 20041114: Same-Pole Application of Low- and High-Energy Shock Waves Protects Kidney from Swl-Induced Tissue Injury Lynn R. Willis, Andrew P. Evan, Bret A. Connors, Philip M. Blomgren, Rajash K. Handa, and James E. Lingeman Lynn R. WillisLynn R. Willis More articles by this author , Andrew P. EvanAndrew P. Evan More articles by this author , Bret A. ConnorsBret A. Connors More articles by this author , Philip M. BlomgrenPhilip M. Blomgren More articles by this author , Rajash K. HandaRajash K. Handa More articles by this author , and James E. LingemanJames E. Lingeman More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)38351-4AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1114: Same-Pole Application of Low- and High-Energy Shock Waves Protects Kidney from Swl-Induced Tissue Injury." The Journal of Urology, 171(4S), p. 294 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 294 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Lynn R. Willis More articles by this author Andrew P. Evan More articles by this author Bret A. Connors More articles by this author Philip M. Blomgren More articles by this author Rajash K. Handa More articles by this author James E. Lingeman More articles by this author Expand All Advertisement PDF downloadLoading ...

Stone comminution and tissue damage in lithotripsy are sensitive to the acoustic field within the kidney, yet knowledge of shock waves in vivo is limited. We have made measurements of lithotripsy shock waves inside pigs with small hydrophones constructed of a 25-microm PVDF membrane stretched over a 21-mm diameter ring. A thin layer of silicone rubber was used to isolate the membrane electrically from pig fluid. A hydrophone was positioned around the pig kidney following a flank incision. Hydrophones were placed on either the anterior (shock wave entrance) or the posterior (shock wave exit) surface of the left kidney. Fluoroscopic imaging was used to orient the hydrophone perpendicular to the shock wave. For each pig, the voltage settings (12-24 kV) and the position of the shock wave focus within the kidney were varied. Waveforms measured within the pig had a shape very similar to those measured in water, but the peak pressure was about 70% of that in water. The focal region in vivo was 82 mm x 20 mm, larger than that measured in vitro (57 mm x 12 mm). It appeared that a combination of nonlinear effects and inhomogeneities in the tissue broadened the focus of the lithotripter. The shock rise time was on the order of 100 ns, substantially more than the rise time measured in water, and was attributed to higher absorption in tissue.

PURPOSE:In studies to understand better the role of cavitation in kidney trauma associated with shock wave lithotripsy we assessed structural and functional markers of kidney injury when animals were exposed to modified shock waves (pressure release reflector shock pulses) that suppress cavitation. Experiments were also performed in isolated red blood cells, an in vitro test system that is a sensitive indicator of cavitation mediated shock wave damage.MATERIALS AND METHODS:We treated 6-week-old anesthetized pigs with shock wave lithotripsy using an unmodified HM3 lithotriptor (Dornier Medical Systems, Marietta, Georgia) fitted with its standard brass ellipsoidal reflector (rigid reflector) or with a pressure release reflector insert. The pressure release reflector transposes the compressive and tensile phases of the lithotriptor shock pulse without otherwise altering the positive pressure or negative pressure components of the shock wave. Thus, with the pressure release reflector the amplitude of the incident shock wave is not changed but cavitation in the acoustic field is stifled. The lower pole of the right kidney was treated with 2,000 shocks at 24 kV. Glomerular filtration rate, renal plasma flow and tubular extraction of para-aminohippurate were measured in the 2 kidneys 1 hour before and 1 and 4 hours after shock wave lithotripsy, followed by the removal of each kidney for morphological analysis. In vitro studies assessed shock wave induced lysis to red blood cells in response to rigid or pressure release reflector shock pulses.RESULTS:Sham shock wave lithotripsy had no significant effect on kidney morphology, renal hemodynamics or para-aminohippurate extraction. Shock waves administered with the standard rigid reflector induced a characteristic morphological lesion and functional changes that included bilateral reduction in renal plasma flow, and unilateral reduction in the glomerular filtration rate and para-aminohippurate extraction. When the pressure release reflector was used, the morphological lesion was limited to hemorrhage of vasa recta vessels near the tips of renal papillae and the only change in kidney function was a decrease in the glomerular filtration rate at the 1 and 4-hour periods in shock wave treated kidneys. Red blood cell lysis in vitro was significantly lower with the pressure release reflector than with the rigid reflector.CONCLUSIONS:These data demonstrate that shock wave lithotripsy damage to the kidney is reduced when cavitation is suppressed. This finding supports the idea that cavitation has a prominent role in shock wave lithotripsy trauma.

Extracotporeal shock wave lithotripsy (SWL) can injure tissue and decrease blood flow in the SWL-treated kidney, both tissue and functional effects being largely localized to the region targeted with shock waves (SWs). A novel method of limiting SWL-induced tissue injury is to employ the "protection" protocol, where the kidney is pretreated with low-energy SWs prior to the application of a standard clinical dose of high-energy SWs. Resistive index measurements of renal vascular resistance/impedance to blood flow during SWL treatment protocols revealed that a standard clinical dose of high-energy SWs did not alter RI during SW application. However, there was an interaction between low- and high-energy SWL treatment phases of the "protection" protocol such that an increase in RI (vasoconstriction) was observed during the later half of SUt application, a time when tissue damage is occurring during the standard high-energy SWL protocol. We suggest that renal vasoconstriction may be responsible for reducing the degree of tissue damage that normally results from a standard clinical dose of high-energy SWs.

PURPOSE:The present study tested the hypothesis that renal disease potentiates the structural/functional changes induced by a clinical dose of shockwaves.MATERIALS AND METHODS:Experimental pyelonephritis was induced in 6- to 8-week-old pigs before treatment with 2,000 shocks at 24 kV. These pigs were divided into two groups according to whether they were infected with a highly virulent (Group 1) or less virulent (Group 2) inoculation of E. coli. All animals were imaged by MR prior to SWL as a means of documenting the extent of pyelonephritis and immediately after SWL to examine the lesion produced by the shockwaves. The glomerular filtration rate (GFR), renal plasma flow (RPF) and para-aminohippurate (PAH) extraction were determined bilaterally on day 30 (Group 1) or day 80 (Group 2).RESULTS:In group 2, urine flow and sodium excretion were reduced by 50% from baseline in the shocked kidneys at both 1 and 4 hours post-SWL. A sustained reduction in RPF through 4 hours post-SWL was noted in the shocked kidneys in Group 1, but RPF was significantly reduced only at the 1-hour determination in Group 2. Large, consistent reductions in GFR were evident at 1 and 4 hours post-SWL in shocked and unshocked kidneys of Group 2 and in the shocked kidneys of Group 1. No significant changes were noted in PAH extraction.CONCLUSION:Acute pyelonephritis exaggerated the effect of a clinical dose of shockwaves on renal hemodynamics. This effect suggests that renal disease may be risk factor for SWL-induced injury.

The relationship between kidney size and impaired renal function induced by shock-wave lithotripsy (SWL) was examined in 6- and 10-wk-old anesthetized pigs. Each pig received 2000 shock waves, 24 kV, or sham SWL to the lower pole calyx of one kidney. Bilateral GFR, renal plasma flow (RPF), and para-aminohippurate extraction was measured 1 h before and 1 and 4 h after SWL. The kidneys were then removed for morphometric analysis. Mean kidney weights were 66.1+/-2.7 g (n = 9) and 103.1+/-3.3 g (n = 8) in the SWL groups, and 60.1+/-2.6 g (n = 9) and 82.3+/-4.0 g (n = 9) in the sham-SWL groups. SWL-induced lesions occupied a significantly greater volume of the small kidneys (6.1+/-1.7 vol % versus 1.5+/-0.2 vol% in the large kidneys). RPF was significantly reduced by SWL in small and large kidneys, but to a significantly greater extent in small kidneys. RPF was also significantly reduced in the contralateral kidneys of both groups, but only at 1 h after SWL. SWL significantly reduced GFR to similar degrees in both kidneys of both groups, regardless of kidney size. Para-aminohippurate extraction was likewise reduced to similar degrees in both groups, but this effect was evident only in the SWL-treated kidneys, and only in the pole to which the shock waves had been applied. The injury induced by SWL affected a larger fraction of small kidneys than large ones, and the renal vasoconstriction induced by SWL was greatest in small kidneys.

SWL to one kidney causes localized tissue damage and impairment of tubular function, but reduces renal plasma flow (RPF) in both kidneys. We examined the effect of SWL voltage (kV) and inversion of the waveform (IW) on these localized and bilateral effects of SWL. Five-week-old pigs were anesthetized for either sham-SWL or SWL (2000 shocks, unmodified HM3) at 12, 18, or 24 kV or 2000 shocks, 24 kV, with a reflector that inverts the waveform. RPF and tubular extraction of PAH (EPAH) were measured 1 h before and 1 and 4 h after SWL. EPAH estimates tubular secretion function. SWL significantly reduced RPF to similar degrees at each kV. EPAH was not significantly reduced in the 12-kV group, but was reduced to progressively greater degrees in the 18 and 24 kV groups. IW eliminated ultrasonic evidence of cavitation, produced minimal tissue damage, and eliminated the reduction of EPAH. It did not eliminate the reduction of RPF. The data suggest that shock-wave voltage and cavitation may be related to the tissue injury and reduced EPAH induced by SWL, but suggests that neither may be directly related to the impairment of RPF. [Work supported by NIH, PO1 DK43881.]

This study tested the hypothesis that the effects of SWL on hemodynamics in solitary kidneys differ from those in kidneys of binephric animals. Five female miniature pigs (Pitman-Moore, 6 months of age, 30-35 kg) were anesthetized for unilateral nephrectomy. Seven pigs served as binephric controls. Two weeks later, each pig was anesthetized, prepared for unilateral or bilateral urine collections, and subjected to SWL (Dornier HM3, 2000 shocks, 24 kV). Clearances of inulin (glomerular filtration rate; GFR) and para-aminohippurate (renal plasma flow; RPF) were measured 1 hour prior to and 1, 4, and 24 hours after SWL. The GFR and RPF were higher in uninephrectomized than in intact pigs at all time points. In both groups, SWL reduced GFR and RPF. In the binephric pigs, RPF was reduced at all times post-SWL, but in the uninephrectomized pigs, RPF was returning toward baseline by 4 hours post-SWL and was not different from baseline at 24 hours. A comparison of whole-animal GFR and RPF (righ plus left clearances in binephric pigs v solitary renal clearances in uninephrectomized pigs) showed that whole-animal GFR and RPF did not differ between the groups before or after SWL. Compensatory renal hypertrophy and improved hemodynamics in solitary kidneys may acutely attenuate the renal vasoconstrictive effect of SWL. The long-term consequences of the compensatory changes are unknown.

Open surgery for removal of upper urinary tract stones has long been associated with a high morbidity and mortality. So when shock wave (SW) lithotripsy (SWL) was introduced in the early 1980s, the climate was right for acceptance of a noninvasive method for stone comminution. The growth in popularity of SWL was extremely rapid, based in part on the perception that it was entirely safe [1]. Now, after a decade of clinical SWL, experience tells us differently. SWL may be very effective at breaking kidney stones, but it can also cause severe renal trauma that can lead to irreversible long-term complications [2, 3].