Biomedical subjects

Abby Borow

Publications and source records attributed to Abby Borow.

4 recordsLinked to original sources

PubMed2004

Inhibition of hyperreflexia by vaginally administered oxybutynin: a novel rabbit model.

PURPOSE: The rabbit has proved to be an excellent model in which to study lower urinary tract function and pathological mechanisms involved in specific forms of lower urinary tract dysfunctions, including those involved with partial outlet obstruction (benign prostatic hyperplasia), erectile dysfunction, bladder instability and ischemic bladder disease. The current study describes a model of bladder instability induced in female rabbits and its use in developing a novel form of vaginal treatment for this instability. MATERIALS AND METHODS: A total of 18 female New Zealand White rabbits were used for this experiment. Each rabbit was anesthetized and the carotid artery was cannulated for blood pressure monitoring. The bladder dome was catheterized for monitoring bladder pressure and for cystometry. A ligature was placed around the urethra just distal to the bladder neck to prevent leakage through the urethra and generate unstable bladder contractions. After initial cystometry the bladder was emptied and then filled to 30 ml. Acetylcholine (Ach) was administered into the vesical artery at 15-minute intervals for 2 hours. Hyperreflexia usually developed within 30 minutes. Vaginal oxybutynin (low and high dose) was applied and the effect on cystometry, the response to Ach, and the amplitude and frequency of hyperreflexia was determined. RESULTS: Each dose of oxybutynin increased bladder capacity and improved compliance. The high oxybutynin dose completely inhibited the response to Ach and significantly decreased micturition pressure. The high dose decreased uninhibited bladder contraction peak pressure in a time dependent manner to a greater extent than it decreased uninhibited contraction frequency. The low dose of oxybutynin had no effect on micturition pressure, significantly inhibited the response to Ach and hyperreflexia amplitude to approximately 40% of control values, and had little effect on hyperreflexia frequency. CONCLUSIONS: Vaginally delivered oxybutynin was effective in improving bladder compliance, inhibiting intra-arterial Ach stimulated bladder contractions and significantly decreasing the amplitude of hyperreflexia. Vaginal oxybutynin had a more potent effect on the evoked response to Ach and on hyperreflexia than it did on micturition pressure.

Administration, Intravaginal↗

PubMed2003

Effectiveness of vaginally administered oxybutynin on rabbit bladder function.

OBJECTIVES: To demonstrate the effectiveness of vaginally delivered oxybutynin on bladder function. Oxybutynin has been used for treatment of urge urinary incontinence for more than 20 years. METHODS: Thirty female New Zealand White rabbits were used for this experiment. Each rabbit was anesthetized, and the carotid artery was cannulated for blood pressure monitoring. The bladder dome was catheterized for both monitoring of bladder pressure and cystometry. After initial cystometry, acetylcholine (ACh) was injected into the vesical artery at 15-minute intervals for 4 hours. Cystometry was performed at the 2-hour mark and at the end of each experiment (4 hours). After the third ACh administration, vaginal or oral oxybutynin was given and the effect on the response to ACh, blood pressure, and cystometry was observed. RESULTS: The high dose of oxybutynin completely inhibited the response to ACh and significantly inhibited the micturition reflex. A 45% inhibition of micturition pressure occurred at the intermediate dose. Little effect on compliance after the low dose and a significant increase in compliance after the mid-dose occurred. Both the low and intermediate doses of oxybutynin reduced the response to ACh to approximately 50% of control. No blood pressure effects of vaginal oxybutynin were noted for any concentration. Oral oxybutynin showed very similar effects to that of the intermediate vaginal dose. CONCLUSIONS: Vaginally delivered oxybutynin was effective in decreasing bladder compliance and inhibiting intra-arterial ACh-stimulated bladder contractions with little or no effect on the vascular effect of ACh.

Acetylcholine↗

PubMed2003

Effect of DHLA on response of isolated rat urinary bladder to repetitive field stimulation.

Lipoic acid is an essential coenzyme in the oxidation of pyruvate and alpha-ketoglutarate. It is easily converted to its reduced form, dihydrolipoic acid (DHLA), in vivo thereby forming a redox pair. DHLA is important in the maintenance and integrity of specific neuronal and subcellular membranes. In the present study we investigated the effect of DHLA on the response of isolated rat bladder strips to repetitive field stimulation (FS), a method used to exhaust synaptic stores of acetylcholine resulting in nerve and synaptic damage. Isolated strips of rat urinary bladders were separated into 4 groups. Group 1 strips were incubated with choline + acetyl-CoA; Group 2 strips with choline, acetyl-CoA + DHLA; and Group 3 with DHLA. Group 4 strips were controls. All strips in Groups 1-3 were subjected to 2 h of repetitive FS followed by 2 h of recovery. DHLA had no effect on the progressive decrease in contractile response observed during repetitive stimulation. However, strips incubated in the presence of DHLA showed a significantly greater degree of recovery than strips incubated in the absence of DHLA. We believe that the protection of the contractile response is related to DHLA's ability to protect nerve and/or muscle membranes from oxidative damage.

8,11,14-Eicosatrienoic Acid↗

PubMed2002

Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder.

PURPOSE: Experimental partial bladder outlet obstruction in rats and rabbits drives the bladder through 3 sequential responses, referred to as hypertrophy, compensation and decompensation. The hypertrophy phase, which is a period of rapid bladder growth, has previously been shown to be accompanied by a significant increase in bladder blood flow in rats and rabbits in a manner that likely supports the bladder cell growth process. However, chronic periods of obstruction in the rabbit have been shown to reduce significantly bladder blood flow, especially to the detrusor smooth muscle, corresponding with a loss of bladder contractile function or decompensation in these animals. We determined the effects of chronic 1 to 4-week partial outlet obstruction on rat bladder blood flow and directly correlated them with hypoxia in the rat bladder. MATERIALS AND METHODS: Rats underwent surgical partial bladder outlet obstruction under anesthesia. At weekly intervals after surgery relative blood flow to the bladder and spleen was measured by a fluorescent microsphere infusion technique. Sham operated rats were also studied 2 and 4 weeks following surgery. In a second experiment groups of similarly obstructed rats were treated with Hypoxyprobe-1 (Natural Pharmacia International, Inc., Research Triangle Park, North Carolina), a chemical probe for hypoxia, 3 days, 1 and 2 weeks after partial bladder outlet obstruction. The bladders were subsequently fixed and immunostained using a monoclonal antibody that detects Hypoxyprobe-1 adducts that are selectively formed in hypoxic cells. RESULTS: Neither bladder weight nor bladder relative blood flow was affected by sham surgery. Likewise, control and sham obstructed rat bladders were found to be free of Hypoxyprobe-1 reactive areas. In contrast, obstructed rats had significantly increased bladder weight at all time points. Relative weight of the obstructed rat bladders indicates the response to mild-moderate obstruction. Bladder relative blood flow in obstructed rats was significantly elevated 1 and 2 weeks after partial bladder outlet obstruction but it returned to almost control levels by 3 and 4 weeks. Hypoxyprobe-1 staining demonstrated a sequential transition of hypoxia from bladder mucosa and submucosal regions at 3 days to muscularis and serosal fibroblasts 1 week and finally to smooth muscle cells by 2 weeks after obstruction. CONCLUSIONS: In contrast to the rabbit model, global blood flow in the mild-moderate chronically obstructed rat bladder was found to be higher or nearly equivalent to blood flow in unobstructed control rat bladders. However, even in the presence of normal or above normal blood flow focal regions of hypoxia were still observed in obstructed rat bladders and these regions changed with time. These results provide a reason to understand better why rats are more resistant to the onset of bladder decompensation than rabbits and support the concept that hypoxia is involved in bladder remodeling as well as in progressive functional impairment of the bladder after partial bladder outlet obstruction.

Animals↗