Bret A Connors

Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA

Are you Bret A Connors?

Claim your profile

Publications (37)91.43 Total impact

  • Article: Evaluation of the LithoGold LG-380 Lithotripter: In Vitro Acoustic Characterization and Assessment of Renal Injury in the Pig Model.
    [show abstract] [hide abstract]
    ABSTRACT: Purpose: Conduct a laboratory evaluation of a novel low-pressure, broad focal zone electrohydraulic lithotripter (TRT LG-380). Methods: Mapping of the acoustic field of the LG-380, along with a Dornier HM3, a Storz Modulith SLX, and a XiXin CS2012 (XX-ES) lithotripter were performed using a fiber optic hydrophone. A pig model was used to assess renal response to 3,000 SWs administered by a multi-step power ramping protocol at 60 SW/min, and when animals were treated at the maximum power setting at 120 SW/min. Injury to the kidney was assessed by quantitation of lesion size and routine measures of renal function. Results: SW amplitudes for the LG-380 ranged from (P+/P-) 7/-1.8 MPa at PL-1 to 21/-4 MPa at PL-11 while focal width measured ~20 mm, wider than the HM3 (8 mm), SLX (2.6 mm) or XX-ES (18 mm). There was gradual narrowing of the focal width to ~10 mm after 5,000 SWs, but this had negligible effect on breakage of model stones, as stones positioned at the periphery of the focal volume (10 mm off-axis) broke nearly as well as stones at the target point. Kidney injury measured less than 0.1% FRV (functional renal volume) for pigs treated using a gradual power ramping protocol at 60 SW/min and when SWs were delivered at maximum power at 120 SW/min. Conclusions: The LG-380 exhibits the acoustic characteristics of a low-pressure, wide focal zone lithotripter and has the broadest focal width of any lithotripter yet reported. Although there was a gradual narrowing of focal width as the electrode aged, the efficiency of stone breakage was not affected. As injury to the kidney was minimal when treatment followed either the recommended slow SW-rate multi-step ramping protocol or when all SWs were delivered at fast SW-rate using maximum power, this appears to be a relatively safe lithotripter.
    Journal of endourology / Endourological Society 12/2012; · 1.75 Impact Factor
  • Article: Optimising an escalating shockwave amplitude treatment strategy to protect the kidney from injury during shockwave lithotripsy.
    [show abstract] [hide abstract]
    ABSTRACT: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Animal studies have shown that one approach to reduce SWL-induced renal injury is to pause treatment for 3-4 min early in the SWL-treatment protocol. However, there is typically no pause in treatment during clinical lithotripsy. We show in a porcine model that a pause in SWL treatment is unnecessary to achieve a reduction in renal injury if treatment is begun at a low power setting that generates low-amplitude SWs, and given continuously for ≈4 min before applying higher-amplitude SWs. OBJECTIVE: •  To test the idea that a pause (≈3 min) in the delivery of shockwaves (SWs) soon after the initiation of SW lithotripsy (SWL) is unnecessary for achieving a reduction in renal injury, if treatment is begun at a low power setting that generates low-amplitude SWs. MATERIALS AND METHODS: •  Anaesthetised female pigs were assigned to one of three SWL treatment protocols that did not involve a pause in SW delivery of >10 s (2000 SWs at 24 kV; 100 SWs at 12 kV +≈10-s pause + 2000 SWs at 24 kV; 500 SWs at 12 kV +≈10-s pause + 2000 SWs at 24 kV). •  All SWs were delivered at 120 SWs/min using an unmodified Dornier HM3 lithotripter. •  Renal function was measured before and after SWL. •  The kidneys were then processed for quantification of the SWL-induced haemorrhagic lesion. Values for lesion size were compared to previous data collected from pigs in which treatment included a 3-min pause in SW delivery. RESULTS: •  All SWL treatment protocols produced a similar degree of vasoconstriction (23-41% reduction in glomerular filtration rate and effective renal plasma flow) in the SW-treated kidney. •  The mean renal lesion in pigs treated with 100 low-amplitude SWs delivered before the main dose of 2000 high-amplitude SWs (2.27% functional renal volume [FRV]) was statistically similar to that measured for pigs treated with 2000 SWs all at high-amplitude (3.29% FRV). •  However, pigs treated with 500 low-amplitude SWs before the main SW dose had a significantly smaller lesion (0.44% FRV) that was comparable with the lesion in pigs from a previous study in which there was a 3-min pause in treatment separating a smaller initial dose of 100 low-amplitude SWs from the main dose of 2000 high-amplitude SWs (0.46% FRV). The time between the initiation of the low - and high-amplitude SWs was ≈4 min for these latter two groups compared with ≈1 min when there was negligible pause after the initial 100 low-amplitude SWs in the protocol. CONCLUSIONS: •  Pig kidneys treated by SWL using a two-step low-to-high power ramping protocol were protected from injury with negligible pause between steps, provided the time between the initiation of low-amplitude SWs and switching to high-amplitude SWs was ≈4 min. •  Comparison with results from previous studies shows that protection can be achieved using various step-wise treatment scenarios in which either the initial dose of SWs is delivered at low-amplitude for ≈4 min, or there is a definitive pause before resuming SW treatment at higher amplitude. •  Thus, we conclude that renal protection can be achieved without instituting a pause in SWL treatment. It remains prudent to consider that renal protection depends on the acoustic and temporal properties of SWs administered at the beginning stages of a SWL ramping protocol, and that this may differ according to the lithotripter being used.
    BJU International 05/2012; · 2.84 Impact Factor
  • Article: Evaluation of shock wave lithotripsy injury in the pig using a narrow focal zone lithotriptor.
    [show abstract] [hide abstract]
    ABSTRACT: What's known on the subject? and What does the study add? Of all the SW lithotriptors manufactured to date, more research studies have been conducted on and more is known about the injury (both description of injury and how to manipulate injury size) produced by the Dornier HM-3 than any other machine. From this information have come suggestions for treatment protocols to reduce shock wave (SW)-induced injury for use in stone clinics. By contrast, much less is known about the injury produced by narrow-focus and high-pressure lithotriptors like the Storz Modulith SLX. In fact, a careful study looking at the morphology of the injury produced by the SLX itself is lacking, as is any study exploring ways to reduce renal injury by manipulating SW delivery variables of this lithotriptor. The present study quantitates the lesion size and describes the morphology of the injury produced by the SLX. In addition, we report that reducing the SW delivery rate, a manoeuvre known to lower injury in the HM-3, does not reduce lesion size in the SLX. •  To assess renal injury in a pig model after treatment with a clinical dose of shock waves using a narrow focal zone (≈3 mm) lithotriptor (Modulith SLX, Karl Storz Lithotripsy). •  The left kidney of anaesthetized female pigs were treated with 2000 or 4000 shock waves (SWs) at 120 SWs/min, or 2000 SWs at 60 SWs/min using the Storz SLX. •  Measures of renal function (glomerular filtration rate and renal plasma flow) were collected before and 1 h after shock wave lithotripsy (SWL) and the kidneys were harvested for histological analysis and morphometric quantitation of haemorrhage in the renal parenchyma with lesion size expressed as a percentage of functional renal volume (FRV). •  A fibre-optic probe hydrophone was used to determine acoustic output and map the focal width of the lithotriptor. •  Data for the SLX were compared with data from a previously published study in which pigs of the same age (7-8 weeks) were treated (2000 SWs at 120 or 60 SWs/min) using an unmodified Dornier HM3 lithotriptor. •  Treatment with the SLX produced a highly focused lesion running from cortex to medulla and often spanning the full thickness of the kidney. Unlike the diffuse interstitial haemorrhage observed with the HM3, the SLX lesion bore a blood-filled core of near-complete tissue disruption devoid of histologically recognizable kidney structure. •  Despite the intensity of tissue destruction at the core of the lesion, measures of lesion size based on macroscopic determination of haemorrhage in the parenchyma were not significantly different from kidneys treated using the HM3 (2000 SWs, 120 SWs/min: SLX, 1.86 ± 0.52% FRV; HM3, 3.93 ± 1.29% FRV). •  Doubling the SW dose of the SLX from 2000 to 4000 SWs did not significantly increase lesion size. In addition, slowing the firing rate of the SLX to 60 SWs/min did not reduce the size of the lesion (2.16 ± 0.96% FRV) compared with treatment at 120 SWs/min, as was the case with the HM3 (0.42 ± 0.23% FRV vs 3.93 ± 1.29% FRV). •  Renal function fell significantly below baseline in all treated groups but was similar for both lithotriptors. •  Focal width of the SLX (≈2.6 mm) was about one-third that of the HM3 (≈8 mm) while peak pressures were higher (SLX at power level 9: P+≈90 MPa, P-≈-12 MPa; HM3 at 24 kV: P+≈46 MPa, P-≈-8 MPa). •  The lesion produced by the SLX (narrow focal width, high acoustic pressure) was a more focused, more intense form of tissue damage than occurs with the HM3. •  Slowing the SW rate to 60 SWs/min, a strategy shown to be effective in reducing injury with the HM3, was not protective with the SLX. •  These findings suggest that the focal width and acoustic output of a lithotriptor affect the renal response to SWL.
    BJU International 04/2012; 110(9):1376-85. · 2.84 Impact Factor
  • Article: Pretreatment with low-energy shock waves reduces the renal oxidative stress and inflammation caused by high-energy shock wave lithotripsy.
    [show abstract] [hide abstract]
    ABSTRACT: The purpose of this study was to determine if pretreatment of porcine kidneys with low-energy shock waves (SWs) prior to delivery of a clinical dose of 2,000 SWs reduces or prevents shock wave lithotripsy (SWL)-induced acute oxidative stress and inflammation in the treated kidney. Pigs (7-8 weeks old) received 2,000 SWs at 24 kV (120 SW/min) with or without pretreatment with 100 SWs at 12 kV/2 Hz to the lower pole calyx of one kidney using the HM3. Four hours post-treatment, selected samples of renal tissue were frozen for analysis of cytokine, interleukin-6 (IL-6), and stress response protein, heme oxygenase-1 (HO-1). Urine samples were taken before and after treatment for analysis of tumor necrosis factor-α (TNF-α). Treatment with 2,000 SWs with or without pretreatment caused a statistically significant elevation of HO-1 and IL-6 in the renal medulla localized to the focal zone of the lithotripter. However, the increase in HO-1 and IL-6 was significantly reduced using the pretreatment protocol compared to no pretreatment. Urinary excretion of TNF-α increased significantly (p < 0.05) from baseline for pigs receiving 2,000 SWs alone; however, this effect was completely abolished with the pretreatment protocol. We conclude that pretreatment of the kidney with a low dose of low-energy SWs prior to delivery of a clinical dose of SWs reduces, but does not completely prevent, SWL-induced acute renal oxidative stress and inflammation.
    Urological Research 03/2011; 39(6):437-42. · 1.23 Impact Factor
  • Article: Effect of shock wave number on renal oxidative stress and inflammation.
    [show abstract] [hide abstract]
    ABSTRACT: OBJECTIVE To determine if the magnitude of the acute injury response to shock-wave lithotripsy (SWL) depends on the number of SWs delivered to the kidney, as SWL causes acute renal oxidative stress and inflammation which are most severe in the portion of the kidney within the focal zone of the lithotripter. MATERIALS AND METHODS Pigs (7-8 weeks old) received 500, 1000 or 2000 SWs at 24 kV from a lithotripter to the lower pole calyx of one kidney. At 4 h after treatment the kidneys were removed, and samples of cortex and medulla were frozen for analysis of the cytokine, interleukin-6, and for the stress response protein, heme oxygenase-1 (HO-1). Urine samples taken before and after treatment were analysed for the inflammatory cytokine, tumour necrosis factor-α. For comparison, we included previously published cytokine data from pigs exposed to sham treatment. RESULTS Treatment with either 1000 or 2000 SWs caused a significant induction of HO-1 in the renal medulla within the focal zone of the lithotripter (F2, 1000 SWs, P < 0.05; 2000 SWs, P < 0.001). Interleukin-6 was also significantly elevated in the renal medulla of the pigs that received either 1000 or 2000 SWs (P < 0.05 and <0.001, respectively). Linear dose-response modelling showed a significant correlation between the HO-1 and interleukin-6 responses with SW dose (P < 0.001). Urinary excretion of tumour necrosis factor-α from the lithotripsy-treated kidney increased only for pigs that received 2000 SWs (P < 0.05). CONCLUSION The magnitude of renal oxidative stress and inflammatory response in the medulla increased with the number of SWs. However, it is not known if the HO-1 response is beneficial or deleterious; determining that will inform us whether SWL-induced renal injury can be assessed by quantifying markers of oxidative stress and inflammation.
    BJU International 04/2010; 107(2):318-22. · 2.84 Impact Factor
  • Article: Time-course for recovery of renal function after unilateral (single-tract) percutaneous access in the pig.
    [show abstract] [hide abstract]
    ABSTRACT: The immediate (1-5 hours) response to percutaneous renal access (PERC) in pigs is vasoconstriction in the treated kidney. The present study determined the longer-term (72 hours) consequences of this surgical procedure. Adult female pigs were anesthetized, and bilateral glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urine flow rate, and sodium excretion rate were measured before and 1 hour after sham PERC or unilateral, single-tract PERC using a balloon dilator system. Animals were allowed to regain consciousness and were then anesthetized 72 hours later for final measurements of bilateral renal hemodynamic and excretory function together with renal para-aminohippuric acid (PAH) extraction (a measure of tubular organic anion transport efficiency). Bilateral renal hemodynamics were unchanged in the sham-PERC-treated pigs over the 72-hour observation period. In contrast, both GFR and ERPF were reduced by approximately 55% in the PERC-treated kidney within 1 hour of access, and returned to pre-PERC levels within 72 hours. Renal hemodynamics were not significantly altered in the opposite, untreated kidney of the PERC-treated pigs. Renal PAH extraction was decreased in PERC-treated kidneys at 72 hours post-PERC. Both sham-PERC-treated and PERC-treated animals showed similar falls in urine flow rate and sodium excretion rate immediately after treatment and at 72 hours after PERC. Renal vasoconstriction characterized the acute response of the treated kidney to unilateral PERC, whereas impaired tubular function (reduced PAH extraction) with near-normal GFR and ERPF characterizes the later (72 hours) response to PERC.
    Journal of endourology / Endourological Society 02/2010; 24(2):283-8. · 1.75 Impact Factor
  • Article: Renal functional effects of multiple-tract percutaneous access.
    [show abstract] [hide abstract]
    ABSTRACT: Percutaneous nephrolithotomy (PCNL) can involve establishing more than one access into the urinary collecting system. The present study examined whether multiple percutaneous accesses results in a more severe reduction in renal function than that after single-percutaneous access. Adult female pigs were anesthetized, and percutaneous access to the left urinary collecting system was achieved by puncturing the lower pole calyx (single-tract access, n = 16) or serially puncturing the lower pole, interpolar region, and upper pole calyces [multiple (three)-tract access, n = 11]. Renal function measurements included glomerular filtration rate and effective renal plasma flow, and were taken immediately before and 1.5 and 4.5 hours after percutaneous access. We also examined glomerular function in a group of adult patients with normal preoperative serum creatinine (Cr) levels (<or=1.4 mg/dL) who underwent either unilateral single-tract PCNL (23 patients) or unilateral multiple (two)-tract PCNL (10 patients). Access tracts were dilated to 30F with a NephroMax balloon dilator system in animal and human patients. Single- and multiple-tract percutaneous access procedures in pigs resulted in a similar renal functional response; both glomerular filtration rate and effective renal plasma flow significantly declined by approximately 60% immediately after access and remained depressed throughout the experimental observation period. A retrospective analysis of patients with normal serum Crs (<or=1.4 mg/dL) who underwent single- or multiple-tract PCNL demonstrated that the procedures produced similar and significant increases in serum Cr on postoperative day 1 (0.33 +/- 0.09 [standard error of mean] mg/dL and 0.39 +/- 0.11 mg/dL, respectively) and day 2 (0.33 +/- 0.09 mg/dL and 0.25 +/- 0.09 mg/dL, respectively). Multiple-tract access does not lead to a more severe reduction in renal function than single-tract access; that is, the acute renal hemodynamic response to PCNL appears independent of the number of access tracts.
    Journal of endourology / Endourological Society 11/2009; 23(12):1951-6. · 1.75 Impact Factor
  • Article: Renal functional effects of simultaneous bilateral single-tract percutaneous access in pigs.
    [show abstract] [hide abstract]
    ABSTRACT: To present our findings of simultaneous bilateral percutaneous nephrolithotomy (sbPCNL) on bilateral renal haemodynamic and excretory function in an in vivo pig model, as despite sbPCNL being a treatment strategy for patients with bilateral renal stones, the functional response of both kidneys to such a procedure is unknown. Nine anaesthetized female pigs ( approximately 70 kg) had a single-tract PCNL procedure in the left kidney and then the right kidney in one session (sbPCNL). Percutaneous access was achieved by a 30 F balloon dilator system. Bilateral renal function was measured before, 1.5 and 4.5 h after sbPCNL and included glomerular filtration rate (GFR), effective renal plasma flow (RPF), renal extraction of para-aminohippurate (EPAH, a measure of the efficiency of tubular organic anion transport), urine flow (UV), absolute sodium excretion (UNaV) and fractional sodium excretion (FENa). Both kidneys had similar baseline haemodynamic and excretory function, and showed comparable changes after sbPCNL. Bilateral GFR and RPF decreased by approximately 35% at 1.5 and 4.5 h after sbPCNL; EPAH was reduced to a similar degree in both kidneys at 1.5 h after sbPCNL and remained depressed throughout the observation period; bilateral UV and UNaV progressively decreased by approximately 30% and approximately 60% at 1.5 and 4.5 h after sbPCNL, respectively; bilateral FENa did not significantly change at 1.5 h after sbPCNL but decreased significantly by approximately 50% at 4.5 h. Both kidneys responded in a similar fashion after sbPCNL, with declines in haemodynamic and excretory function. These bilateral functional responses were comparable to those previously reported after unilateral PCNL, and help to reduce concerns that PCNL of both kidneys in one session could lead to greater functional complications, at least acutely.
    BJU International 07/2009; 105(1):125-8. · 2.84 Impact Factor
  • Article: Renal heme oxygenase-1 upregulation after shock wave lithotripsy.
    [show abstract] [hide abstract]
    ABSTRACT: Shock wave lithotripsy (SWL) is known to induce oxidative stress and a rapid inflammatory response in renal tissue. The purpose of this study was to determine the location and quantify markers for oxidative stress and inflammation in a porcine model of acute SWL-induced renal injury. The lower pole calyx of left kidneys of female pigs received 2000 shock waves at 24 kV2 Hz from a Dornier HM3 lithotripter and subsequently monitored for 4 h. Heme oxygenase-1 protein (HO-1) was measured in renal microsomes by Western blot. Renal medulla HO-1beta-actin ratios were 1.186 +/- 0.48 for treated pole (F2), 0.293 +/- 0.23 for treated kidney upper pole, and 0.122 +/- 0.075 for contralateral kidney (n=6). Thus, we observed an eightfold induction of HO-1 in renal medulla at F2 compared to the upper pole medulla of the treated kidney and the contralateral kidney medulla. In contrast, renal cortex at F2 did not show a similar HO-1 induction. The highly localized HO-1 induction in SWL-treated renal medulla parallels our previously reported finding of interleukin-6. These data together suggest that an early inflammatory response and oxidative stress appear primarily in the treated renal medulla within 4 h after SWL. [Work supported by NIH].
    The Journal of the Acoustical Society of America 05/2009; 125(4):2620. · 1.55 Impact Factor
  • Article: Low-energy shock wave pretreatment results in greater vasoconstriction and less injury in the kidney compared to high-energy shock wave lithotripsy treatment alone.
    [show abstract] [hide abstract]
    ABSTRACT: Pretreating the kidney with low-energy shock waves (SWs) before administering a clinical dose of high-energy SWs has been found to greatly decrease the hemorrhagic lesion that normally results from high-energy shock wave lithotripsy (SWL) treatment alone. We tested the hypothesis that this novel pretreatment SWL protocol results in a greater andor earlier renal vasoconstriction than clinical SWL alone, which could potentially explain the reduced bleeding in the kidney. Anesthetized pigs were treated with a clinical dose of SWs (2000 SWs, 24 kV, 120 SWsmin) or the pretreatment protocol (500 SWs, 12 kV, 120 SWsmin + 3-min pause + 2000 SWs, 24 kV, 120 SWsmin) using the HM3 lithotripter. Sonography (color and pulsed ultrasound) was used to locate a resistance artery within the SW-treated pole of the kidney and to take resistance index (RI) measurements from the blood vessel to estimate the resistanceimpedance to blood flow. The results demonstrated that RI increased (renal vasoconstriction) earlier and greater during the pretreatment protocol compared to normal clinical SWL. Constricted blood vessels would likely be less prone to rupture by SWs and, if broken, would bleed less-resulting in a smaller hemorrhagic lesion.
    The Journal of the Acoustical Society of America 05/2009; 125(4):2621. · 1.55 Impact Factor
  • Article: Shock wave lithotripsy can alter urinary acid-base pH regulation.
    [show abstract] [hide abstract]
    ABSTRACT: The renal papilla is particularly susceptible to injury by shock waves (SWs). Since the papilla is vital for urinary pH regulation, we hypothesized that shock wave lithotripsy (SWL)-induced damage of papillae will alter the pH of the urine. Experiments were conducted in four female adult Gottingen minipigs. The HM3 lithotripter delivered a total of 8000 SWs (24 kV, 120 SWsmin) among all papillae of one kidney, while the untreated, opposite kidney was used as control. The pigs were allowed to recover and 5 weeks later they were anesthetized. Serial urine collections were obtained from the SW-treated and untreated kidney. Urine was collected under mineral oil and immediately tested for its pH. Both kidneys were then perfusion fixed for histological analysis. Urinary pH was 0.17 units greater (P<0.05) in the SW-treated kidney compared to the untreated kidney. Histology showed scarring in all regions of the SW-treated kidney, with thick ascending limbs and collecting ducts having grossly abnormal morphologies indicative of cellular proliferation. These results suggest that SWL-induced injury can cause remodeling of nephron structures and long-term impairment in the regulation of urinary pH.
    The Journal of the Acoustical Society of America 05/2009; 125(4):2622. · 1.55 Impact Factor
  • Article: Extracorporeal shock wave lithotripsy at 60 shock waves/min reduces renal injury in a porcine model.
    [show abstract] [hide abstract]
    ABSTRACT: To determine if extracorporeal shock wave lithotripsy (ESWL) at 60 shock waves (SWs)/min reduces renal damage and haemodynamic impairment compared to treatment at 120 SWs/min. One kidney in each of 19 juvenile pigs (7-8 weeks old) was treated at 120 or at 60 SWs/min (2000 SWs, 24 kV) with an unmodified HM-3 lithotripter (Dornier Medical Systems, Kennesaw, GA, USA). Renal function was determined before and after ESWL treatment by inulin clearance, extraction and clearance of para-aminohippuric acid. Both kidneys were then removed to measure parenchymal lesion size by sectioning the entire kidney and quantifying the size of the haemorrhagic lesion in each slice. ESWL at 60 SWs/min significantly reduced the size of the acute morphological lesion compared to 120 SWs/min (0.42% vs 3.93% of functional renal volume, P = 0.011) and blunted the decrease in glomerular filtration rate and renal plasma flow normally seen after treatment at 120 SWs/min. Treatment at a firing rate of 60 SWs/min produces less morphological injury and causes less alteration in renal haemodynamics than treatment at 120 SWs/min in the pig model of ESWL-induced renal injury.
    BJU International 04/2009; 104(7):1004-8. · 2.84 Impact Factor
  • Article: Localization of renal oxidative stress and inflammatory response after lithotripsy.
    [show abstract] [hide abstract]
    ABSTRACT: OBJECTIVE To determine if the acute renal oxidative stress and inflammation after extracorporeal shock wave lithotripsy (ESWL), thought to be mediated by ischaemia, is most severe in the portion of the kidney within the focal zone of the lithotripter, and if these effects result primarily from ischaemic injury. MATERIALS AND METHODS Pigs (7-8-weeks old) received either 2000 shock waves at 24 kV to the lower-pole calyx of one kidney or unilateral renal ischaemia for 1 h. A third group (sham) received no treatment. Timed urine and blood samples were taken for analysis of lipid peroxidation and the inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). At 4 h after treatment, kidneys were removed and samples of cortex and medulla were frozen for analysis of cytokines and heme oxygenase-1 (HO-1). RESULTS ESWL did not affect urinary excretion of malondialdehyde, but did elicit an eight-fold induction of HO-1 in the portion of the renal medulla within the focal zone of the lithotripter (F2), while remaining unchanged elsewhere in the treated kidney. There was no induction of HO-1 in renal tissue after ischaemia-reperfusion. Urinary excretion of TNF-alpha increased from the lithotripsy-treated kidney by 1 h after treatment, but was unaffected by ischaemia-reperfusion. As with the HO-1 response after lithotripsy, IL-6 increased only in the renal medulla at F2. By contrast, ischaemia-reperfusion increased IL-6 in all samples from the treated kidney. CONCLUSION These findings show that the acute oxidative stress and inflammatory responses to ESWL are localized to the renal medulla at F2. Furthermore, the differing patterns of markers of injury for ESWL and ischaemia-reperfusion suggest that ischaemia is not the principal cause of the injury response after ESWL.
    BJU International 02/2009; 103(11):1562-8. · 2.84 Impact Factor
  • Article: Assessment of renal injury with a clinical dual head lithotriptor delivering 240 shock waves per minute.
    [show abstract] [hide abstract]
    ABSTRACT: Lithotriptors with 2 treatment heads deliver shock waves along separate paths. Firing 1 head and then the other in alternating mode has been suggested as a strategy to treat stones twice as rapidly as with conventional shock wave lithotripsy. Because the shock wave rate is known to have a role in shock wave lithotripsy induced injury, and given that treatment using 2 separate shock wave sources exposes more renal tissue to shock wave energy than treatment with a conventional lithotriptor, we assessed renal trauma in pigs following treatment at rapid rate (240 shock waves per minute and 120 shock waves per minute per head) using a Duet lithotriptor (Direx Medical Systems, Petach Tikva, Israel) fired in alternating mode. Eight adult female pigs (Hardin Farms, Danville, Indiana) each were treated with sham shock wave lithotripsy or 2,400 shock waves delivered in alternating mode (1,200 shock waves per head, 120 shock waves per minute per head and 240 shock waves per minute overall at a power level of 10) to the lower renal pole. Renal functional parameters, including glomerular filtration rate and effective renal plasma flow, were determined before and 1 hour after shock wave lithotripsy. The kidneys were perfusion fixed in situ and the hemorrhagic lesion was quantified as a percent of functional renal volume. Shock wave treatment resulted in no significant change in renal function and the response was similar to the functional response seen in sham shock wave treated animals. In 6 pigs treated with alternating mode the renal lesion was small at a mean +/- SEM of 0.22% +/- 0.09% of functional renal volume. Kidney tissue and function were minimally affected by a clinical dose of shock waves delivered in alternating mode (120 shock waves per minute per head and 240 shock waves per minute overall) with a Duet lithotriptor. These observations decrease concern that dual head lithotripsy at a rapid rate is inherently dangerous.
    The Journal of urology 01/2009; 181(2):884-9. · 4.02 Impact Factor
  • Article: Pretreatment with low-energy shock waves induces renal vasoconstriction during standard shock wave lithotripsy (SWL): a treatment protocol known to reduce SWL-induced renal injury.
    [show abstract] [hide abstract]
    ABSTRACT: To test the hypothesis that the pretreatment of the kidney with low-energy shock waves (SWs) will induce renal vasoconstriction sooner than a standard clinical dose of high-energy SWs, thus providing a potential mechanism by which the pretreatment SW lithotripsy (SWL) protocol reduces tissue injury. Female farm pigs (6-weeks-old) were anaesthetized with isoflurane and the lower pole of the right kidney treated with SWs using a conventional electrohydraulic lithotripter (HM3, Dornier GmbH, Germany). Pulsed Doppler ultrasonography was used to measure renal resistive index (RI) in blood vessels as a measure of resistance/impedance to blood flow. RI was recorded from one intralobar artery located in the targeted pole of the kidney, and measurements taken from pigs given sham SW treatment (Group 1; no SWs, four pigs), a standard clinical dose of high-energy SWs (Group 2; 2000 SWs, 24 kV, 120 SWs/min, seven pigs), low-energy SW pretreatment followed by high-energy SWL (Group 3; 500 SWs, 12 kV, 120 SWs/min + 2000 SWs, 24 kV, 120 SWs/min, eight pigs) and low-energy SW pretreatment alone (Group 4; 500 SWs, 12 kV, 120 SWs/min, six pigs). Baseline RI (approximately 0.61) was similar for all groups. Pigs receiving sham SW treatment (Group 1) had no significant change in RI. A standard clinical dose of high-energy SWs (Group 2) did not significantly alter RI during treatment, but did increase RI at 45 min after SWL. Low-energy SWs did not alter RI in Group 3 pigs, but subsequent treatment with a standard clinical dose of high-energy SWs resulted in a significantly earlier (at 1000 SWs) and greater (two-fold) rise in RI than that in Group 2 pigs. This rise in RI during the low/high-energy SWL protocol was not due to a delayed vasoconstrictor response of pretreatment, as low-energy SW treatment alone (Group 4) did not increase RI until 65 min after SWL. The pretreatment protocol induces renal vasoconstriction during the period of SW application whereas the standard protocol shows vasoconstriction occurring after SWL. Thus, the earlier and greater rise in RI during the pretreatment protocol may be causally associated with a reduction in tissue injury.
    BJU International 01/2009; 103(9):1270-4. · 2.84 Impact Factor
  • Article: Effect of initial shock wave voltage on shock wave lithotripsy-induced lesion size during step-wise voltage ramping.
    [show abstract] [hide abstract]
    ABSTRACT: To determine if the starting voltage in a step-wise ramping protocol for extracorporeal shock wave lithotripsy (SWL) alters the size of the renal lesion caused by the SWs. To address this question, one kidney from 19 juvenile pigs (aged 7-8 weeks) was treated in an unmodified Dornier HM-3 lithotripter (Dornier Medical Systems, Kennesaw, GA, USA) with either 2000 SWs at 24 kV (standard clinical treatment, 120 SWs/min), 100 SWs at 18 kV followed by 2000 SWs at 24 kV or 100 SWs at 24 kV followed by 2000 SWs at 24 kV. The latter protocols included a 3-4 min interval, between the 100 SWs and the 2000 SWs, used to check the targeting of the focal zone. The kidneys were removed at the end of the experiment so that lesion size could be determined by sectioning the entire kidney and quantifying the amount of haemorrhage in each slice. The average parenchymal lesion for each pig was then determined and a group mean was calculated. Kidneys that received the standard clinical treatment had a mean (sem) lesion size of 3.93 (1.29)% functional renal volume (FRV). The mean lesion size for the 18 kV ramping group was 0.09 (0.01)% FRV, while lesion size for the 24 kV ramping group was 0.51 (0.14)% FRV. The lesion size for both of these groups was significantly smaller than the lesion size in the standard clinical treatment group. The data suggest that initial voltage in a voltage-ramping protocol does not correlate with renal damage. While voltage ramping does reduce injury when compared with SWL with no voltage ramping, starting at low or high voltage produces lesions of the same approximate size. Our findings also suggest that the interval between the initial shocks and the clinical dose of SWs, in our one-step ramping protocol, is important for protecting the kidney against injury.
    BJU International 09/2008; 103(1):104-7. · 2.84 Impact Factor
  • Article: Correlation of vasoconstriction and kidney protection during shock wave lithotripsy.
    [show abstract] [hide abstract]
    ABSTRACT: Kidney injury in lithotripsy can lead to long-term adverse effects, so minimizing injury is beneficial. We have found that injury is significantly reduced when shock wave (SW) administration is halted briefly- 3-minutes-early in treatment. Previous studies have shown that SWs stimulate renal blood vessels to constrict. Therefore, we tested the idea that vasoconstriction mediates SW-induced protection of the kidney. Doppler ultrasound was used to measure resistive index (RI), a ratio of systolic and diastolic velocities, indicating vasoconstriction. RI was determined for single intralobar arteries in targeted porcine kidneys treated by standard versus protection protocols (2,000SW, uninterrupted vs 500SW-3-min pause-2,000SW) using a Dornier-HM3 lithotripter (2Hz, 24kV). Significant differences in RI from baseline within a group and between groups at various time points were determined using mixed-effect models for repeated measures with Holm's step-down method for multiple comparison adjustment. All animals had similar baselines. Sham pigs (no-SWs) showed no significant change in RI. The protection protocol produced a significant rise (p<0.05, n=8) in RI 15 minutes into treatment, while the standard protocol did not yield a significant rise (p<0.05, n=7) until 45 minutes after treatment. Thus, the treatment protocol shown to protect against injury, induces early vasoconstriction. [NIH-DK43881, NSBRI-SMS00402].
    The Journal of the Acoustical Society of America 05/2008; 123(5):3367. · 1.55 Impact Factor
  • Article: Potential for cavitation-mediated tissue damage in shockwave lithotripsy.
    [show abstract] [hide abstract]
    ABSTRACT: Shockwave lithotripsy (SWL) injures renal tissue, and cavitation has been reported to mediate some of these effects. Much of the work characterizing the cavitation injury of SWL has been performed in small animals or in vitro. We describe experiments that promote cavitation during SWL and estimate the spatial distribution of the resulting hemorrhagic lesion in a large-animal (porcine) model of clinical lithotripsy. The lower pole calix of the left kidney in female farm pigs was targeted for SWL with a Dornier HM3 lithotripter. Intraventricular injections of polystyrene microspheres were made before and at intervals during lithotripsy to blanket systemic circulation with cavitation nuclei. Following SWL, the abdominal viscera were inspected and the kidneys were processed for morphologic analysis. Extensive surface hemorrhage occurred over both the targeted and contralateral kidneys, along with widespread petechial hemorrhage over the spleen, intestines, and peritoneum. The targeted kidneys developed subcapsular hematomas. Histology revealed focal and diffuse damage to the targeted kidneys and vascular rupture in both kidneys with complete necrosis of the walls of intralobular arteries and veins. These results demonstrate the potential for unfocused shockwaves to damage blood vessels outside the focal zone of the lithotripter when the vasculature is seeded with cavitation nuclei. The wide distribution of damage suggests that the acoustic field of a lithotripter delivers negative pressures that exceed the cavitation threshold far off the acoustic axis. The findings underscore that conditions permissive for cavitation can lead to dramatic sequelae during SWL.
    Journal of Endourology 02/2008; 22(1):121-6. · 1.85 Impact Factor
  • Source
    Article: Independent assessment of a wide-focus, low-pressure electromagnetic lithotripter: absence of renal bioeffects in the pig.
    [show abstract] [hide abstract]
    ABSTRACT: To assess the renal injury response in a pig model treated with a clinical dose of shock waves (SWs) delivered at a slow rate (27 SW/min) using a novel wide focal zone (18 mm), low acoustic pressure (<20 MPa) electromagnetic lithotripter (Xi Xin-Eisenmenger, XX-ES; Xi Xin Medical Instruments Co. Ltd., Suzhou, PRC). The left kidneys of anaesthetized female pigs were treated with 1500 SWs from either an unmodified electrohydraulic lithotripter (HM3, Dornier MedTech America, Inc., Kennesaw, GA, USA; 18 kV, 30 SW/min) or the XX-ES (9.3 kV, 27 SW/min). Measures of renal function (glomerular filtration rate, GFR, and renal plasma flow) were collected before and after SW lithotripsy, and kidneys were harvested for histological quantification of vascular haemorrhage, expressed as a percentage of the functional renal volume (FRV). A fibre-optic probe hydrophone was used to characterize the acoustic field, and the breakage of gypsum model stones was used to compare the function of the two lithotripters. Kidneys treated with the XX-ES showed no significant change in renal haemodynamic function and no detectable tissue injury. Pigs treated with the HM3 had a modest decline from baseline ( approximately 20%) in both GFR (P > 0.05) and renal plasma flow (P = 0.064) in the treated kidney, but that was not significantly different from the control group. Although most HM3-treated pigs showed no evidence of renal tissue injury, two had focal injury measuring 0.1% FRV, localized to the renal papillae. The width of the focal zone for the XX-ES was approximately 18 mm and that of the HM3 approximately 8 mm. Peak positive pressures at settings used to treat pigs and break model stones were considerably lower for the XX-ES (17 MPa at 9.3 kV) than for the HM3 (37 MPa at 18 kV). The XX-ES required fewer SWs to break stones to completion than did the HM3, with a mean (sd) of 634 (42) and 831 (43) SWs, respectively (P < 0.01). However, conditions were different for these tests because of differences in physical configuration of the two machines. The absence of renal injury with the wide focal zone XX-ES lithotripter operated at low shock pressure and a slow SW rate suggests that this lithotripter would be safe when used at the settings recommended for patient treatment. That the injury was also minimal using the Dornier HM3 lithotripter at a slow SW rate implies that the reduced tissue injury seen with these two machines was because they were operated at a slow SW rate. As recent studies have shown stone breakage to be improved when the focal zone is wider than the stone, a wide focal zone lithotripter operated at low pressure and slow rate has the features necessary to provide better stone breakage with less tissue injury.
    BJU International 02/2008; 101(3):382-8. · 2.84 Impact Factor
  • Article: Renal injury during shock wave lithotripsy is significantly reduced by slowing the rate of shock wave delivery.
    [show abstract] [hide abstract]
    ABSTRACT: To assess the tissue protection afforded by simply reducing the rate of shock wave (SW) delivery, compared with studies in the pig in which SW lithotripsy (SWL)-induced vascular damage was significantly reduced by initiating treatment using low-amplitude SWs. Juvenile pigs (6-7 weeks old) were treated with an unmodified lithotripter (HM3, Dornier Medical Systems, Kennesaw, GA) at either 120 or 30 SW/min. Treatment was to one kidney per pig, with SWs (2000, 24 kV) directed to a lower-pole calyx. After treatment, parenchymal haemorrhage was determined morphometrically and expressed as percentage of functional renal volume (%FRV). Kidneys treated at 120 SW/min had focal to extensive subcapsular haematomas. Parenchymal lesions were found only at the lower pole, but included regions within renal papillae and the cortex. Occasionally, damage extended across the full thickness of the kidney. The lesion in the pigs treated at 120 SW/min occupied a mean (sd) of 4.6 (1.7) %FRV. Kidneys of pigs treated at 30 SW/min showed no surface bleeding. Parenchymal haemorrhage was limited to papillae within the focal volume, and measured 0.08 (0.02) %FRV, a significant (P < 0.005) reduction in injury. Slowing the rate of delivery to 30 SW/min has a dramatic protective effect on the integrity of the kidney vasculature. This finding in our established pig model suggests a potential strategy to improve the safety of lithotripsy. As it was shown that a reduced SW rate also improves the efficiency of stone fragmentation, a slow rate appears to be a means to improve both the safety and efficacy of SWL.
    BJU International 10/2007; 100(3):624-7; discussion 627-8. · 2.84 Impact Factor

Institutions

  • 2003–2011
    • Indiana University-Purdue University Indianapolis
      • • Department of Anatomy and Cell Biology
      • • Department of Pharmacology and Toxicology
      Indianapolis, IN, USA
    • Government of the People's Republic of China
      Beijing, Beijing Shi, China
  • 2002–2008
    • University of Washington Seattle
      • Applied Physics Laboratory
      Seattle, WA, USA
  • 2007
    • Indiana University-Purdue University School of Medicine
      • Pharmacology and Toxicology
      Indianapolis, IN, USA
    • Institute of Anatomy and Cell Biology
      Heidelberg, Baden-Wuerttemberg, Germany
  • 2005
    • University of British Columbia - Vancouver
      • Department of Surgery
      Vancouver, British Columbia, Canada