Browsing by Subject "Integrative biology and physiology"

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    Role of the renal nerves in hypertension
    (2014-11) Foss, Jason David
    High blood pressure (hypertension; HTN) is the leading risk factor for death, yet the precise causes are unclear. The nervous system is known to play a role in some forms of HTN and research has pointed to the kidneys as a likely neural target in HTN. This possibility has been strengthened by recent clinical trials showing that ablation of the renal nerves (renal denervation; RDNX) has a significant antihypertensive effect in drug resistant patients. However, failure of the most recent sham-controlled trial has raised many questions regarding this treatment. Chief among them is whether the antihypertensive effect of RDNX is due to changes in kidney function secondary to ablation of sympathetic (efferent) renal nerves, or due to a reduction in non-renal sympathetic nerve activity secondary to ablation of sensory (afferent) renal nerves. In order to address this question, I first identified an animal model of HTN in which RDNX had an antihypertensive effect. Importantly, I showed that RDNX had roughly the same effect on blood pressure in hypertensive Dahl salt-sensitive (S) rats as has been reported in clinical trials. I then developed and validated a novel method for selective ablation of afferent renal nerves (renal-CAP treatment). Using this method, I showed that afferent renal nerves are not necessary to maintain cardiovascular or sodium/water homeostasis in normotensive rats subjected to dietary sodium loading. We also showed that renal-CAP treatment and complete RDNX caused the same attenuation of deoxycorticosterone-salt HTN, suggesting that the antihypertensive effect of RDNX in this model is due to ablation of afferent renal nerves. Lastly, we showed that RDNX has the same antihypertensive effect in Dahl S rats with mild HTN (after three weeks of high salt feeding) and in those with severe HTN (after nine weeks of high salt feeding). These results suggest that the antihypertensive effect of RDNX in the Dahl S rat is not dependent on duration of high salt feeding or pretreatment blood pressure and that the antihypertensive effect of RDNX in this model is not due to ablation of afferent renal nerves.
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    A study of the sacral anatomy and its implications on the development of a guide to improve the efficacy of locating the S3 Foramen for implantation of a sacral nerve stimulation lead.
    (2011-11) Stetz, Eric Michael
    Urinary incontinence and overactive bladder are medical conditions where the patient either has frequent urges to urinate (urinary urgency-frequency), the inability to urinate despite the feelings of a full bladder (urinary urge incontinence) or the inability to completely empty the bladder (urinary retention). These conditions affect around 72 million people in North America and around 348 million people world wide. The patient population breakdown is around 72% female and 28% male.1 Many options are available for treating urinary incontinence. These include incontinence pads to absorb unintentional voiding episodes, physical therapy, pharmacologic drug therapy, surgical interventions such as urethral slings and sacral nerve stimulation (SNS). Most patients proceed from pads and physical therapy to drugs and finally nerve stimulation. InterStim is the only FDA approved neurostimulation system currently on the market for treating urinary urge incontinence, urinary urgencyfrequency and non-obstructive urinary retention.2 The therapy consists of an implantable neurostimulator (INS) and an associated lead which delivers the electrical stimulation from the INS to the target sacral nerve. One aspect for successful application of SNS therapy is using a foramen needle to locate the S3 sacral foramen and place the lead electrodes adjacent to the S3 sacral nerve. The activities documented in this thesis centered on the collection of sacral anatomy data as a design input for the evaluation of a lead implant template for use in locating the S3 foramen. The project hypothesis is “Will the use of a lead implant template help to improve the efficacy for locating the S3 foramen when implanting a Sacral Nerve Stimulation lead for treating urinary incontinence?". The project was split into two primary studies. The first half of the project centered on an anatomical study of the morphological variation in dry bone sacrum and cadavers. The anatomical study was intended to quantify the amount of variation that needs to be accommodated by the implant template. The second half of the project centered on the efficacy evaluation of the prototype template.