Biomedical subjects

Bret A Connors

Publications and source records attributed to Bret A Connors.

14 recordsLinked to original sources

PubMed2006

Prevention of lithotripsy-induced renal injury by pretreating kidneys with low-energy shock waves.

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% CI -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% CI -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.

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PubMed2006

Acute effects of percutaneous tract dilation on renal function and structure.

BACKGROUND: Percutaneous nephrolithotomy (PCNL) is performed on a routine basis for the rapid and efficient removal of large caliceal stones. After percutaneous puncture, rigid dilators or an inflatable balloon are used to dilate the nephrostomy tract to allow access to the collecting system for stone removal. Little is known of the acute impact of tract dilation procedures on renal function. MATERIALS AND METHODS: We compared renal hemodynamic and excretory function in female pigs immediately before and up to 5 hours after percutaneous nephrostomy (PCN) using sequential Amplatz dilators (N = 8) or Nephromax balloon inflation (N = 7) and control pigs with no PCN access (N = 8). We also examined renal function in patients undergoing PCNL. RESULTS: The two PCN procedures produced a renal lesion of comparable size and morphology, as well as similar changes in renal function. Glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary sodium excretion (U(Na)V) were significantly reduced in Amplatz- and Nephromax-treated kidneys throughout the 5-hour observation period, by about 50%, 60%, and 80%, respectively. In control pigs, GFR and RPF remained stable and U(Na)V declined progressively to about 50% of baseline over the course of the experiment. The contralateral kidney showed changes in renal function similar to those in the PCN-treated or control kidney in all three groups. A retrospective analysis of 196 adults with normal renal function who underwent unilateral PCNL using the Nephromax balloon dilator revealed a significant increase in serum creatinine of 0.14 mg/dL at 1 day. CONCLUSION: Both animal and human studies show that PCN is associated with an acute decline in renal function.

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PubMed2006

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.

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PubMed2005

Cavitation detection during shock-wave lithotripsy.

A system was built to detect cavitation in pig kidney during shock-wave lithotripsy (SWL) with a Dornier HM3 lithotripter. Active detection using echo on B-mode ultrasound, and passive cavitation detection using coincident signals on confocal orthogonal receivers, were used to interrogate the renal collecting system (urine) and the kidney parenchyma (tissue). Cavitation was detected in urine immediately upon shock-wave (SW) administration in urine or urine plus X-ray contrast agent but, in native tissue, cavitation required hundreds of SWs to initiate. Localization of cavitation was confirmed by fluoroscopy, sonography and by thermally marking the kidney using the passive cavitation detection receivers as high-intensity focused ultrasound sources. Cavitation collapse times in tissue and native urine were about the same, but less than in urine after injection of X-ray contrast agent. The finding that cavitation occurs in kidney tissue is a critical step toward determining the mechanisms of tissue injury in SWL.

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PubMed2005

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.

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PubMed2003

Morphological changes induced in the pig kidney by extracorporeal shock wave lithotripsy: nephron injury.

While shock wave lithotripsy (SWL) is known to cause significant damage to the kidney, little is known about the initial injury to cells along the nephron. In this study, one kidney in each of six juvenile pigs (6-7 weeks old) was treated with 1,000 shock waves (at 24 kV) directed at a lower pole calyx with an unmodified HM-3 lithotripter. Three pigs were utilized as sham-controls. Kidneys were fixed by vascular perfusion immediately after SWL or sham-SWL. Three of the treated kidneys were used to quantitate lesion size. Cortical and medullary samples for light (LM) and transmission electron microscopy (TEM) were taken from the focal zone for the shock waves (F2), the contralateral kidney, and the kidneys of sham-SWL pigs. Because preservation of the tissue occurred within minutes of SWL, the initial injury caused by the shock waves could be separated from secondary changes. No tissue damage was observed in contralateral sham-SWL kidneys, but treated kidneys showed signs of injury, with a lesion of 0.2% +/- 0.1% of renal volume. Intraparenchymal hemorrhage and injury to tubules was found at F2 in both the cortex and medulla of SWL-treated kidneys. Tubular injury was always associated with intraparenchymal bleeding, and the range of tissue injury included total destruction of tubules, focal cellular fragmentation, necrosis, cell vacuolization, and membrane blebbing. The initial injury caused by SWL was cellular fragmentation and necrosis. Cellular vacuolization, membrane blebbing, and disorganization of apical brush borders appear to be secondary changes related to hypoxia.

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PubMed2003

Renal nerves mediate changes in contralateral renal blood flow after extracorporeal shockwave lithotripsy.

Renal blood flow falls in both kidneys following delivery of a clinical dose of shockwaves (SW) (2000 SW, 24 kV, Dornier HM3) to only one kidney. The role of renal nerves in this response was examined in a porcine model of renal denervation. Six-week-old pigs underwent unilateral renal denervation. Nerves along the renal artery of one kidney were identified, sectioned and painted with 10% phenol. Two weeks later the pigs were anesthetized and baseline renal function was determined using inulin and PAH clearances. Animals then had either sham-shockwave lithotripsy (SWL) (group 1), SWL to the innervated kidney (group 2) or SWL to the denervated kidney (group 3). Bilateral renal function was again measured 1 and 4 h after SWL. Both kidneys were then removed for analysis of norepinephrine content to validate the denervation. Renal plasma (RPF) flow was significantly reduced in shocked innervated kidneys (group 2) and shocked denervated kidneys (group 3). RPF was not reduced in the unshocked denervated kidneys of group 2. These observations suggest that renal nerves play a pivotal role in modulating the vascular response of the contralateral unshocked kidney to SWL, but only a partial role, if any, in modulating that response in the shocked kidney.

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PubMed2002

Stone fragmentation during shock wave lithotripsy is improved by slowing the shock wave rate: studies with a new animal model.

PURPOSE: The current trend toward ungated shock wave lithotripsy means that more patients are being treated with shock waves delivered at a rapid rate (120 shock waves per minute or greater). However, no benefit of an increased shock wave rate has been shown and in vitro studies indicate that slowing the shock wave rate actually improves stone fragmentation. We tested the effect of the shock wave rate on stone comminution in a new animal model. MATERIALS AND METHODS: Gypsum model stones were inserted via upper pole percutaneous access into the lower pole calix of the kidneys of female pigs weighing approximately 100 pounds. Shock wave lithotripsy was performed (400 shock waves uninterrupted at 20 kV. and 30 or 120 shock waves per minute) 2 hours later using an unmodified HM3 lithotriptor (Dornier Medical Systems, Marietta, Georgia). After en bloc excision of the urinary tract stone fragments were collected and sieved through 2 mm. mesh. The particles were weighed and surface area was determined. RESULTS: Stones treated at 30 shock waves per minute broke more completely than stones treated at 120 shock waves per minute. The percent of fragments greater than 2 mm. was significantly higher for stones treated at the fast rate of 120 versus the slow rate of 30 shock waves per minute (mean +/- SEM 81% +/- 14% versus 45% +/- 12%, p <0.005). When stone fragmentation was expressed as the percent increase in fragment surface area, significantly greater fragmentation occurred at the slower than at the more rapid rate (327% +/- 63% versus 135% +/- 136%, p <0.02). CONCLUSIONS: Slowing the rate of shock wave administration during shock wave lithotripsy significantly improves the efficiency of stone fragmentation in vivo.

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PubMed2002

Kidney damage and renal functional changes are minimized by waveform control that suppresses cavitation in shock wave lithotripsy.

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.

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PubMed2002

Atubular glomeruli in a rat model of polycystic kidney disease.

BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) is associated with a progressive decline in glomerular filtration rate (GFR) that often leads to end-stage renal disease. The basis for this decline in GFR is poorly understood. METHODS: Glomeruli in heterozygous Han:SPRD rats with ADPKD and their normal litter mates were studied by light microscopy, using serial sectioning techniques. The connections of the renal corpuscles to proximal tubules were classified as normal, atrophied, or absent (atubular glomerulus). Renal corpuscles also were examined by scanning electron microscopy. Single nephron glomerular blood flows were determined using microspheres. RESULTS: In the kidneys of six-month-old rats with ADPKD, 50% of the glomeruli were atubular and another 26% were associated with atrophied neck segments; these glomeruli were most often smaller in size than normal. About 16% of the glomeruli were hypertrophied and had normal connections to proximal tubules. Sclerotic changes in cystic kidney glomeruli were usually mild or moderate, and belied the failure of glomerular function. Glomerular blood flow in the cystic kidneys averaged half of normal and was markedly heterogeneous; the majority of small glomeruli displayed very low blood flows and a few showed relatively high blood flows. Fewer glomerular abnormalities were found in rats treated for five months with potassium citrate in their drinking water. CONCLUSIONS: The diminished GFR in the rat with ADPKD can be accounted for largely by the formation of atubular glomeruli. Compensatory glomerular hypertrophy also is present and may contribute to the progression of the renal disease.

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PubMed2002

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.

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PubMed2002

Prefocal alignment improves stone comminution in shockwave lithotripsy.

BACKGROUND: The Dornier HM-3 machine continues to be one of the most effective lithotripters in use. However, tissue damage occurs in most, if not all, shockwave lithotripsy (SWL) treatments. Cavitation appears to contribute to desired stone comminution as well as to undesired tissue damage. Studies of cavitation in electrohydraulic shockwave lithotripters indicate that the greatest cavitation activity occurs, not at the geometric focus, F2, but at a site proximal to F2 by 1 to 3 cm. In clinical practice, however, stones are aligned with F2. MATERIALS AND METHODS: In vitro stone comminution, hemolysis, and free-radical production were assessed along the focal axis, and pig kidneys treated with SWL in vivo were sectioned to determine the extent of hemorrhagic injury along the focal axis. Model gypsum stones received 200 shockwaves in vitro at 18 kV. RESULTS: At F2, the average number of fragments >1.5 mm was 1.3 +/- 0.5, and the weight loss was 11.3 +/- 1.1%. At 2 cm from F2 (F2-2 cm), these values increased to 4 +/- 2.8 and 16.1 +/- 4.2%, respectively. Samples of 10% hematocrit blood were similarly exposed. Hemolysis was equivalent at F2-2 cm (14.7 +/- 2.3%) and F2 (15.2 +/- 3%) but decreased significantly at all other positions. Samples of iodine solution received 1500 shockwaves at 20 kV. Hydroxyl radical production was greatest at F2-2 cm (0.384 +/- 0.035 microM) and decreased significantly distal to this position. The volume of tissue injury in pig kidneys was greatest with prefocal shockwave exposure. CONCLUSION: Stone comminution may be achieved more rapidly without greater tissue damage by a simple shift in stone alignment to F2-2 cm.

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PubMed2000

The effect of discharge voltage on renal injury and impairment caused by lithotripsy in the pig.

The present study was designed to determine the effects of shock wave voltage (kV) on lesion size and renal function induced by shock wave lithotripsy (SWL) in the 6- to 8-wk-old pig. Each SWL-treated pig received 2000 shock waves at 12, 18, or 24 kV to the lower pole calyx of one kidney. A group of sham SWL pigs served as time controls. Bilateral GFR, renal plasma flow (RPF), and para-aminohippurate (PAH) extraction were measured 1 h before and 1 and 4 h after SWL in all treated and sham animals. The kidneys were removed at the end of each experiment for morphometric analysis. The SWL-induced lesion increased significantly in size as shock wave energy was increased from 12 to 24 kV. PAH extraction, a measure of tubular function, was not significantly affected at 12 kV, was transiently reduced at 18 kV, and was reduced for the duration of the experiment at 24 kV. GFR and RPF, however, were significantly and similarly reduced at the 1 h post-SWL period at all three kilovolt levels. At the 4-h post-SWL period, both GFR and RPF had returned to baseline levels. Lesion size and tubular injury were correlated with changes in kilovoltage, while changes in renal hemodynamics were already maximal at the lowest discharge voltage. These findings suggest that renal microvessels are highly sensitive to shock waves and that frank injury to tubules and vessels may be more closely related to discharge energy than is renal blood flow.

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PubMedDate not supplied

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.

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