Independent assessment of a wide-focus, low-pressure electromagnetic lithotripter: absence of renal bioeffects in the pig

OBJECTIVE

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).

MATERIALS AND METHODS

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.

RESULTS

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 (≈ 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 ≈ 18 mm and that of the HM3 ≈ 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.

CONCLUSION

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.     

Shockwave lithotripsy: dose-related effects on renal structure, hemodynamics, and tubular function

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.     

Effect of initial shock wave voltage on shock wave lithotripsy-induced lesion size during step-wise voltage ramping

OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.     

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

OBJECTIVE

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.

MATERIALS AND METHODS

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).

RESULTS

Baseline RI (≈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.

CONCLUSIONS

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.     

Reducing shock number dramatically decreases lesion size in a juvenile kidney model

BACKGROUND AND PURPOSE: Adult stone patients are treated with several thousand lithotripter shockwaves (SWs) in order to pulverize a kidney stone. This typical clinical dose assures that the stone will be fractured completely. However, this same dose induces damage to the kidney, especially pediatric-size kidneys. If increasing SW number is known to increase renal injury and functional impairment, will reducing SW number below typical treatment levels significantly decrease kidney damage and hemodynamic changes? MATERIALS AND METHODS: To address this question, one kidney in each of nine juvenile pigs (6-7 weeks old) was treated with 1000 SWs at 24 kV directed at a lower-pole calix with an unmodified HM-3 lithotripter. Parenchymal-lesion size was determined by sectioning the entire kidney and quantitating the amount of hemorrhage in each slice. Renal function was determined before and after SW treatment by inulin clearance, paraaminohippurate (PAH) extraction, and PAH clearance. The resulting morphologic and functional changes were then compared with those of kidneys that had been treated with a typical clinical dose of 2000 SWs (data previously published; J Am Soc Nephrol 2000;11:310). Eleven pigs were utilized as sham-treated controls. RESULTS: Limiting SW number to 1000 significantly reduced the size of the lesion (by 95%) and reduced the degree of functional change (glomerular filtration rate by 38%, PAH extraction by 73%, renal plasma flow by 46%) compared with kidneys receiving 2000 SWs (an adult dose). CONCLUSIONS: These data support the idea that SW number should be reduced to the lowest number that fractures kidney stones in order to minimize renal injury and functional impairment.     

Why stones break better at slow shockwave rates than at fast rates: in vitro study with a research electrohydraulic lithotripter

BACKGROUND AND PURPOSE: Stones break better when the rate of shockwave (SW) delivery is slowed. It has been hypothesized that the greater cavitation accompanying a fast rate shields pulse propagation, thus interfering with the delivery of SW energy to the stone. We tested this idea by correlating waveforms measured at the SW focus with cavitation viewed using high-speed imaging. MATERIALS AND METHODS: A series of U30 gypsum stones held in a 2-mm mesh basket were exposed to 200 SWs at 30 or 120 SW/min from a research electrohydraulic lithotripter (HM3 clone). Waveforms were collected using a fiberoptic probe hydrophone. High-speed imaging was used to observe cavitation bubbles in the water and at the stone surface. Results: Stone breakage was significantly better at 30 SW/min than at 120 SW/min. The rate had little effect on SW parameters in the water free field. In the presence of particulates released from stones, the positive pressure of the SW remained unaffected, but the trailing tensile phase of the pulse was significantly reduced at 120 SW/min. CONCLUSIONS: Cavitation bubbles do not persist between SWs. Thus, mature bubbles from one pulse do not interfere with the next pulse, even at 120 SW/min. However, cavitation nuclei carried by fine particles released from stones can persist between pulses. These nuclei have little effect on the compressive wave but seed cavitation under the influence of the tensile wave. Bubble growth draws energy from the negative-pressure phase of the SW, reducing its amplitude. This likely affects the dynamics of cavitation bubble clusters at the stone surface, reducing the effectiveness of bubble action in stone comminution.     

Extracorporeal shock wave lithotripsy at 60 shock waves/min reduces renal injury in a porcine model

OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.     

Pretreatment with low-energy shock waves reduces the renal oxidative stress and inflammation caused by high-energy shock wave lithotripsy

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.     

Renal injury during shock wave lithotripsy is significantly reduced by slowing the rate of shock wave delivery

OBJECTIVE: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.     

Shock wave lithotripsy of stones implanted in the proximal ureter of the pig

PURPOSE: Ureteral stones can be difficult to treat with shock wave (SW) lithotripsy. A strategy for lithotripsy of proximal ureteral stones is to push them back into the renal pelvis prior to administering SWs. However, push-back is invasive and not always possible. Since there are few clues to suggest how best to treat ureteral stones with SWs in situ, we developed an animal model for research on lithotripsy for ureteral stones. MATERIALS AND METHODS: Gypsum model stones were implanted bilaterally in the proximal ureter and renal calix of the pig via percutaneous access. Lithotripsy was performed using a HM3 lithotripter (Dornier Medical Systems, Marietta, Georgia) and stones at each location were treated with the same dose (400 SWs, 20 kV and 30 SWs per minute). Fragments were collected and the percent increase in projected surface area of the particles was determined. RESULTS: The breakage (mean percent area increase) of stones implanted in the proximal ureter was significantly less than that of stones located in the renal calix treated with the same dose of shock waves (134% vs 327%, p <0.001). Also, stones that were fully confined by the ureter did not break as well as stones located at the ureteropelvic junction. This indicates that the physical environment surrounding a stone can have a significant effect on the efficiency of SW action. CONCLUSIONS: The observation that stones implanted in the ureter showed decreased breakage compared with stones in the kidney is consistent with clinical experience. This finding is a valuable and even essential prerequisite for any experimental animal model system intended for the study of SW action in the breakage of ureteral stones.     

Efficacy of the Duet lithotripter using two energy sources for stone fragmentation by shockwaves: an in vitro study

PURPOSE: To evaluate the efficacy of the Duet lithotripter's novel design of two independent spark-plug generator/reflector systems focused at a common F2. The apparatus allows either simultaneous delivery of shockwaves from both generators (resulting in a per-shock energy delivery at F2 equal to that delivered by its single generator at about 24 kV), alternating (between the two generators), or single-generator delivery of shockwaves at various energy levels and rates. MATERIALS AND METHODS: Eighty-five phantom gypsum stones (volume 786 mm3 each) were placed in a net-like basket and immersed in a specially designed waterbath coupled with the Duet lithotripter (Direx Medical Systems Ltd., Petach Tikva, Israel). Shockwaves were delivered at rates of either 60 or 120 per minute and at intensities of 16 or 22.8 kV (electrohydraulic). Energy was delivered either separately from each generator, in an alternating mode, or simultaneously from both generators. The number of shocks required to fragment the stones sufficiently to allow all of the pieces to fall through the basket holes (complete fragmentation) was recorded. RESULTS: The number of shocks required for complete fragmentation in the alternate mode (120 shocks/min, each generator rate 60/min; 22.8kV) was lower than with the single generator, 112 +/- 19 v 134 +/- 18 (at a rate of 120/min; 22.8 kV). The simultaneous mode of dual generator shockwave delivery was more effective than the traditional single generator (114 +/- 28 shocks at a rate of 120/min, 16 kV v 159 +/- 40 shocks at a rate 120/min; 22.8kV). CONCLUSION: The Duet lithotripter is more effective when used in a simultaneous or alternating mode than is the classical single mode of shock delivery, with the added benefit of shorter treatment time.     

Effect of shock wave number on renal oxidative stress and inflammation

What’s known on the subject? and What does the study add? Oxidative stress and inflammation are tissue‐ and cell‐level components of shock wave lithotripsy (SWL)‐induced acute renal injury, which we recently showed to be localized principally to the medulla within the focal zone of the lithotripter. This study reports that the magnitude of the oxidative stress and inflammation observed in the medulla after SWL is dependent on the number of shock waves delivered to the kidney, indicating that this is a sensitive measure of renal injury caused by shock waves. 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.     

Extracorporeal shock wave lithotripsy using Dornier modified HM3 lithotripter comparison with the results by Dornier HM3 lithotripter

Ninety-four kidneys with renal stones less than or equal to 20 mm in diameter were treated by extracorporeal shock wave litotripsy (ESWL) using a Dornier modified HM3 lithotripter and the results were compared with those of 98 kidneys with similar size stones treated with a Dornier HM3 lithotripter. The Dornier modified HM3 lithotripter is equipped with a new type of shock wave generator with a reduced capacity for 30% less pressure peakes at the same voltage. It has an enlarged ellipsoid leading to a smaller focus and a reduced pressure per area at the shock wave entry into the skin. All treatments of modified HM3 litotripter series were performed under only intravenous analgosedation, without epidural anesthesia. The number of shock waves in the modified HM3 series ranged 900 to 6000, with the mean values of 2863 +/- 1234, which was 1.55 times as that in the Dornier HM3 series. Complete disintegration was achieved in 94 of 94 modified HM3 series kidneys and 98 of 98 kidneys of HM3 series. Complete removal of the stone was done at 72.6% in the modified HM3 series and at 70.4% in the HM3 series 3 months after ESWL. There were no severe complications in both modified HM3 series and HM3 series. Renal damage caused by ESWL was monitored by the level of urinary enzyme, N-acetyl-beta-glucosaminidase (NAG) and beta 2 microglobulin (beta 2MG) and the level of urinary protein. The levels of NAG, beta 2MG and urinary protein in the HM3 series were higher than those of the modified HM3 series.(ABSTRACT TRUNCATED AT 250 WORDS)     

Percutaneous stone implantation in the pig kidney: a new animal model for lithotripsy research

PURPOSE: This report describes a new animal model for research on the parameters of shockwave delivery and the mechanisms of shockwave action in SWL. MATERIALS AND METHODS: Female pigs (approximately 45 kg) were anesthetized for creation of an upper pole peripheral caliceal access. The tract was dilated with a 30F Nephromax balloon and Amplatz sheath, and a 24F rigid nephroscope was used to guide a gypsum artificial stone into a lower pole calix. An internal ureteral stent was then placed. After a 2-hour recovery period, lithotripsy was performed using an unmodified Dornier HM3 lithotripter. Following SWL, en bloc excision of the urinary tract was performed, and the stone fragments were collected. RESULTS: As observed by nephroscopy, most stones were surrounded by urine that was free of clot or debris. Urine output was >1 mL/kg per minute by the time the animal was positioned for SWL after a 2-hour observation period. When the conditions of shockwave (SW) exposure were 400 SWs, 20 kV, and 120 SW/min, the efficiency of stone fragment recovery was 85% +/- 2% (N = 6 stones). CONCLUSIONS: This procedure provides a minimally invasive method for placement of model stones of clinically relevant size within the pig kidney. Stone implantation is efficient and permits experiments to be conducted in 1 day. Stone fragmentation can be quantitated, and the animal can serve as its own control. Long-term experiments are also feasible. Overall, this new animal model is appropriate for experimentation on the parameters of SW delivery in SWL.     

Cellular effects of piezoelectric versus electrohydraulic high energy shock waves.

High energy shock waves produced by a piezoelectric lithotripter, (EDAP LT.01) and an electrohydraulic lithotripter, (Dornier HM3) were examined for their effects on Chinese hamster ovary cells in suspension. The EDAP caused acute lactate dehydrogenase release, consistent with severe membrane disruption in a proportion of cells, with the remaining proportion of cells replicating normally as measured by clonogenic assay. Similarly, the Dornier also caused lactate dehydrogenase release. However, a significant proportion of cells which remained "viable" after Dornier treatment, (intact to lactate dehydrogenase), did not replicate by clonogenic assay. The Dornier HM3 lithotripter has been reported to produce free radicals in aqueous solution. In the current investigation, we could not detect significant free radical formation from the EDAP LT.01. Chinese hamster ovary cell killing by the Dornier HM3 was significantly augmented by radiosensitizers, 5-iodo-2-deoxyuridine or buthionine sulfoximine, while radioprotectors cysteamine and WR-1065 had no protective effect. EDAP cell killing was not influenced by either radioprotectors or radiosensitizers. The mechanism of in vitro cytotoxicity differs between piezoelectric and electrohydraulic high energy shock wave delivery.     

A comparison of renal damage induced by varying modes of shock wave generation.

To evaluate for the possible differences in the extent of pathologic injury occurring following treatment with various lithotripsy modalities, we subjected rabbits to treatment on either an electrohydraulic, electromechanical, or piezoelectric lithotripter. Functional evaluations by enzymuria failed to reveal any difference in the extent of damage between the lithotripters. Pathologic evaluation of the kidneys revealed that both electrohydraulic and electromechanical lithotripsy resulted in an increased instance of acute subcapsular hematoma and fibrosis when compared to piezoelectric treated kidneys (p less than 0.001). Despite the definitive differences noted in the acute animals, there was no significant variation in the area of permanent renal damage that occurred between the various lithotripters.     

Effects of Extracorporeal Shock Wave Lithotripsy to One Kidney on Bilateral Glomerular Filtration Rate and PAH Clearance in Minipigs

Purpose

This study examined the acute time course of effects of extracorporeal shock wave lithotripsy (ESWL)¹ on renal hemodynamics in anesthetized minipigs with and without pretreatment with verapamil.

Materials and Methods

We applied ESWL (2000 shocks, 24 kV, unmodified Dornier HM3), to the right kidneys of isoflurane-anesthetized female pigs. Urine flow and renal hemodynamics were monitored from each kidney via ureteral balloon catheters. Arterial blood pressure and bilateral urine flow, glomerular filtration rate (GFR, inulin clearance) and renal plasma flow (RPF, para-aminohippurate clearance) were monitored for 45 minutes before ESWL, and at 1, 4 and 24 hours after ESWL.

Results

Treatment with ESWL consistently caused unilateral hematuria and subcapsular renal hematomas in the shocked kidneys and significantly reduced GFR and RPF in those kidneys at 1 and 4 hours after ESWL. Urine flow was reduced through 24 hours in the shocked kidneys. Renal plasma flow, but not GFR, was significantly reduced in the contralateral (unshocked) kidneys at 1 and 4 hours after ESWL to the other kidneys. Verapamil blunted the ESWL-induced reductions of urine flow, GFR and RPF in the shocked kidneys and eliminated the reduction of RPF in the unshocked kidneys.

Conclusions

These experiments demonstrate that ESWL to 1 kidney acutely impaired hemodynamics in both kidneys and that verapamil attenuated the response in the shocked kidneys and eliminated it in the contralateral unshocked kidneys.     

Cystine calculi: correlation of CT-visible structure,CT number,and stone morphology with fragmentation by shock wave lithotripsy

Cystine stones are often highly resistant to shock wave lithotripsy (SWL), but it has been reported that cystine stones of "rough" morphology are actually quite susceptible to SWL. Based on the observation that rough cystine stones contain void regions that are visible by helical computed tomographic (CT) imaging, we hypothesized that the internal structure of cystine stones would correlate with the susceptibility of stones to SWL. Cystine stones with average diameters between 4 and 7 mm were scanned using micro and helical CT, classified morphologically according to published criteria, and broken in a research electrohydraulic lithotripter, with fragments sieved through a 2 mm mesh every 50 SWs. Stones with regions of low X-ray attenuation visible on helical CT required only 650 +/- 312 SW/g for total comminution, while those that did not show CT-visible internal structure required 1,046 +/- 307 SW/g (mean +/- SD, P < 0.004). In addition, both average and minimum values for CT number (in Hounsfield units, HU) correlated with SW/g to comminution (P < 0.003 and P < 0.0003, respectively), and these relationships were independent of stone size. This study also confirmed the relationship between the morphological criteria of Bhatta et al. (J Urol 142:937-940, 1989) and cystine stone fragility: Rough stones required 609 +/- 244 SW/g (n = 11), smooth stones 1,109 +/- 308 SW/g (n = 8), and stones intermediate in morphology 869 +/- 384 SW/g (n = 7; rough different from smooth, P < 0.005). In conclusion, cystine stones that appeared homogeneous by helical CT required 61% more SWs for comminution than did stones showing regions of low X-ray attenuation. These findings demonstrate the feasibility of using helical CT to identify cystine stones that will be susceptible to SWL.     

Conversion of an HM3 lithotripter into a research device

PURPOSE: To describe the conversion of a Dornier HM3 lithotripter into a research device and evaluate its performance. MATERIALS AND METHODS: A used HM3 lithotripter was donated to our university by the St. Thomas' Hospital in London. It was disassembled, shipped to our laboratory, partially assembled, and modified as a research lithotripter. Pressure measurements at several positions and kidney stone model fragmentation tests were performed to evaluate the modified system. Results were compared with information published by other authors and data obtained in our laboratory using another electrohydraulic research lithotripter. RESULTS: Pressure records showed typical lithotripter waveforms with a rapid rise to about 50 MPa, followed by decay to a negative peak of approximately 9 MPa. Maximum compressional peaks were obtained at F2 and 25 mm below F2. Kidney stone model fragmentation was typical for electrohydraulic shockwave lithotripters. CONCLUSIONS: Comparison of pressure measurements with data obtained by other authors on the same lithotripter several years ago indicate that the pressure waveform has not changed significantly. A much smaller water tank, a small X-Y-Z positioner, and no X-ray imaging system facilitate the use of this shockwave generator for in vitro experiments with small samples such as vials containing cell suspensions, having the advantage of a reliable, well-known, and well-characterized commercial shockwave generator.