Bret A. Connors, PhD
Assistant Scientist in Anatomy & Cell Biology
POSITIONS AND HONORS.
1977-1979 Laboratory Assistant, Dept. of Biology, Earlham College
1979-1983 Research Technician, Dept. of Anatomy, IU School of Medicine
1983-1990 Associate Instructor, Dept. of Anatomy, IU School of Medicine
1990-1991 Graduate Fellowship, Dept. of Anatomy, IU School of Medicine
1992-1994 Postdoctoral Training, Depts. of Physiol. and Biophys., and Anatomy, IU School of Medicine
1994- Assistant Scientist, Dept. of Anatomy and Cell Biology, IU School of Medicine
1998-present American Association of Anatomists
CONTRIBUTION TO SCIENCE.
C1. I did pioneering work to utilize SEM to examine and quantitate ultrastructural features in the kidney and the ultrastructure of vascular smooth muscle. The kidney work included quantitating cell types along the collecting duct from SEM micrographs in neonatal and mature kidneys of the rabbit (reference1). The vascular smooth muscle work employed newly developed (at that time) tissue digestion protocols to remove extracellular matrix components to allow direct visualization of smooth muscle cells. SEM was then used to quantitate the dimensions of the vascular smooth muscle by techniques also developed in our laboratory (references 3 and 4).
1. Evan AP, LM Satlin, VH Gattone, BA Connors, GJ Schwartz. (1991) Postnatal maturation of the rabbit renal collecting duct. II. Morphologic observations. Am J Physiol 30(1):F91-F107.
2. Evan AP, VH Gattone, BA Connors. (1992) Ultrastructural features of the rabbit proximal tubule. Arch Histol Cytol 55(supplement):139-145.
3. Connors BA, HG Bohlen, AP Evan. (1995) Vascular endothelium and smooth muscle remodeling accompanies hypertrophy of intestinal arterioles in streptozotocin diabetic rats. Microvas Res 49:340-349.
4. Evan AP, BA Connors. (1996) Morphometric analysis of vascular smooth muscle cells by scanning electron microscopy. Intern Rev of Exp Path 36:31-52.
C2. My earliest work with extracorporeal shock wave lithotripsy (SWL) and stone disease was directed at understanding the injury created by SWL. At that time most investigators, and almost all physicians, in the field of shock wave treatment of renal stones believed that lithotripsy was benign and caused little or no injury to the kidney during routine SWL procedures. I was part of a group of researchers who investigated the biological effects of lithotripsy treatment using animal models. We documented that SWL caused significant injury to every treated kidney and determined that the primary injury caused by SWL was rupture of blood vessels followed by interstitial hemorrhage. This work changed the perception of SWL related renal injury in the urological community.
1. Evan AP, LR Willis, BA Connors, JA McAteer, JE Lingeman. (1991) Renal injury following extracorporeal shock wave lithotripsy. J Endourol 5(1):25-35.
2. Blomgren P, BA Connors, JE Lingeman, LR Willis, AP Evan. (1997) Quantitation of shock wave lithotripsy-induced lesion in small and large pig kidneys. Anat Rec 249:341-348.
3. Willis LR, AP Evan, BA Connors, PM Blomgren, NS Fineberg, JE Lingeman. (1999) Relationship between kidney size, renal injury and renal impairment induced by shock wave lithotripsy. J Am Soc Neph 10:1753-1762.
4. Shao Y, BA Connors, AP Evan, LR Willis, DA Lifshitz, JE Lingeman. (2003) Morphological changes induced in the pig kidney by extracorporeal shock wave lithotripsy: nephron injury. Anat Rec 275A:979-989.
C3. To further understand what was causing SWL injury, I began a series of collaborations to explore the physics and biology behind shock wave (SW) damage. Our research provided unique information to the scientific community. This work included detailed measurements of SWs inside kidneys indicating that SW pressures were reduced by approximately 20% when passing through the body wall. We also determined that SW treatment stimulates renal nerves and that this nerve activity contributes to the dramatic reduction in blood flow associated with SWL treatment. Perhaps the most fascinating results to come from these collaborative studies involved the detection of cavitation inside of renal tissue. We were able to show that cavitation occurs in tissue after sufficient injury has produced pools of blood in the treated area.
1. Cleveland RO, DA Lifshitz, BA Connors, AP Evan, LR Willis, LA Crum. (1998) In vivo measurements of lithotripsy shock waves in pigs. Ultrasound Med Bio 24:293-306.
2. Connors BA, AP Evan, LR Willis, PM Blomgren, JE Lingeman, NS Fineberg. (2000) The effect of discharge voltage on renal injury and impairment caused by lithotripsy in the pig. J Am Soc Neph 11:310-318.
3. Connors BA, AP Evan, LR Willis, JR Simon, NS Fineberg, DA Lifshitz, AL Shalhav, RF Paterson, RL Kuo, JE Lingeman. (2003) Renal nerves mediate changes in contralateral renal blood flow after extracorporeal shock wave lithotripsy. Nephron Physiol 95:p67-p75.
4. Bailey MR, YA Pishchalnikov, OA Sapozhnikov, RO Cleveland, JA McAteer, NA Miller, IV Pishchalnikova, BA Connors, LA Crum, AP Evan. (2005) Cavitation detection during shock wave lithotripsy. Ultrasound Med Biol 31:1245-1256.
C4. With the realization that a clinical dose of SWL causes renal injury, our group set about to find ways to reduce SW injury by manipulating the parameters of treatment. Using animal models we were able to show that SW injury could be reduced by slowing the delivery of SWs during treatment, or by introducing a time pause at the beginning of a SWL procedure. The urology community has embraced this information and many groups have modified their treatment protocols to include the treatment modifications we have suggested.
1. Willis LR, AP Evan, BA Connors, PM Blomgren, RK Handa, JE Lingeman. (2006) Prevention of lithotripsy-induced renal injury by pretreating kidneys with low-energy shock waves. J Am Soc Nephrol 17:663-673.
2. Evan AP, JA McAteer, BA Connors, PM Blomgren, JE Lingeman. (2007) Renal injury in SWL is significantly reduced by slowing the rate of shock wave delivery. BJU Int 100:624-628.
3. Connors BA, AP Evan, PM Blomgren, RK Handa, LR Willis, S Gao. (2009) Effect of initial shock wave voltage on SWL-induced lesion size during step-wise voltage ramping. BJU Int 103:104-107. PMCID: PMC2605209.
4. Connors BA, AP Evan, PM Blomgren, RK Handa, LR Willis, S Gao, JA McAteer, JE Lingeman. (2009) Extracorporeal shock wave lithotripsy at 60 shock waves/min reduces renal injury in a porcine model. BJU Int 104:1004-1008. PMCID: PMC2888935.
C5. With the realization that a clinical dose of SWL causes renal injury, our group also set about to find ways to increase the effectiveness of SWL by manipulating the parameters of treatment. Again, we were able to suggest ways of improving the effectiveness of SWL. We have also recently warned the urology community that SWL treatment may be promoting the formation of kidney stones (reference 4). This information makes efforts to improve the safety and effectiveness of SWL essential for promoting the long-term health of patients.
1. Paterson RF, DA Lifshitz, JE Lingeman, AP Evan, BA Connors, NS Fineberg, JC Williams, JA McAteer. (2002) Stone fragmentation during Shock Wave Lithotripsy is improved by slowing the shock wave rate: studies with a new animal model. J Urol 168:2211-2215.
2. Sokolov DL, MR Bailey, LA Crum, PM Blomgren, BA Connors, AP Evan. (2002) Pre-focal alignment improves stone comminution in shock wave lithotripsy. J Endourol 16:709-715.
3. Paterson RF, SC Kim, RL Kuo, JE Lingeman, AP Evan, BA Connors, JC Williams, JA McAteer. (2005) Shock wave lithotripsy of stones implanted in the proximal ureter of the pig. J Urol 173:1391-1394.
4. Evan AP, EM Worcester, BA Connors, RK Handa, JE Lingeman, FL Coe. (2015) Mechanism by which shock wave lithotripsy can promote formation of human calcium phosphate stones. Am J Physiol 308(8)F938-F949:. PMCID:PMC4398833.
Current Research Support:
2-P01-DK-56788 (Coe, F.L.) 8/1/2014-7/31/2017
Pathophysiology and Histopathology of Nephrolithiasis
Role: Principal Investigator (on subcontract)
The goal of this proposal is to understand how kidney stones form by looking at the mechanisms of stone formation associated with tubular plugging and stone formation associated with Randall's plaques.
2-P01-DK-43881-20 (Bailey, M.R.) 7/1/2014-6/30/2019
Innovative Strategies for Improved Outcomes in Nephrolithiasis
The goals of this research include improving single session treatment effectiveness of extracorporeal shock wave lithotripsy, and to develop ultrasound-based technologies and treatment protocols to non-invasively remove kidney stones.
Selected Completed Research Support:
2-R44-DK-089703-02A1 (Schaefer, R.) 9/1/2014-8/31/2015
Sparker Array for Improved Electrohydraulic Lithotripsy (EHL)
Role: Principal Investigator (on subcontract)
The overall goal of this research is to develop and test a sparker array system as a new device to produce shock waves for extracorporeal shock wave lithotripsy.
2-P01-DK-43881-15 (McAteer, J.E.) 7/1/2009-6/30/2014
Strategies for Improved Shock Wave Lithotripsy
The overall goal of this research is to determine the physical mechanisms of stone comminution and the cause and consequences of shock wave-induced renal injury so that strategies can be devised to minimize or eliminate adverse effects while improving efficacy of shock wave lithotripsy.
I have two main areas of research. The first area centers on understanding kidney structure and function in diseases such as diabetes, hypertension, and in models of renal injury. My current research involves understanding the injury created by shock wave lithotripsy treatment. Shock wave lithotripsy (SWL) is used to fracture kidney stones. It is an effective treatment for most small stones and is widely used throughout the world. However, SWL also causes injury to the kidney being treated. The research that I am involved in seeks to define and measure the structural and functional changes resulting from SWL. In addition, I am trying to determine if altering the parameters of treatment will change the amount of injury. My second main area of research centers on understanding how kidney stones form and what drives the repeated development of stones in some individuals. Kidney stone disease is not one disease, by may diseases which all result in calculus formation in the kidney. Determining what triggers the deposition of mineral deposits will help determine how to treat each type of stone disease.