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Biomedical subjects

L J O'Connor

Publications and source records attributed to L J O'Connor.

7 recordsLinked to original sources

Protective effect of vitamin E on the response of the rabbit bladder to partial outlet obstruction.

PURPOSE: There is increasing evidence that ischemia/reperfusion is a major etiological factor in the progression of bladder dysfunction after partial outlet obstruction. If this evidence is correct, treatment with an antioxidant should be beneficial in rabbits subjected to partial outlet obstruction. We designed the current study to determine if diets high in alpha-tocopherol protected the rabbit bladder against dysfunction induced by partial outlet obstruction. MATERIALS AND METHODS: A total of 32 rabbits were separated into 4 groups of 8. Groups 1 and 2 were placed on a diet enriched with 1,000 IU/kg. alpha-tocopherol, and groups 3 and 4 were fed a regular diet containing 44 IU/kg. alpha-tocopherol. After 4 weeks partial outlet obstruction was created in groups 1 and 3, while groups 2 and 4 underwent sham operation. After 4 weeks of obstruction the rabbits were anesthetized and the bladders were rapidly excised. Four longitudinal strips obtained from the bladder body were used for contractility studies. The balance of the bladder body was separated between muscle and mucosa. Each section was frozen and stored at -70C for analysis of malondialdehyde as a measure of peroxidation and for alpha-tocopherol concentrations. RESULTS: Feeding rabbits a diet high in alpha-tocopherol resulted in significant protection against the development of contractile dysfunction after partial outlet obstruction. The protective effect of alpha-tocopherol was related to significantly decreased malondialdehyde and significantly increased tissue concentrations of alpha-tocopherol. CONCLUSIONS: These data indicate that a major etiology of bladder dysfunction secondary to partial outlet obstruction is related to free radical generation and resultant membrane lipid peroxidation.

Analysis of Variance↗

Comparative physiology and biochemistry of rat and rabbit urinary bladder.

OBJECTIVE: To compare directly the biochemistry and contractile responses of rat and rabbit bladder to different stimuli. Materials and methods Sexually mature male New Zealand White rabbits and Sprague Dawley rats were compared. Each bladder was excised while the animal was anaesthetized; longitudinal bladder strips were cut and then mounted in an organ bath. Tension (2 g) was placed on all strips and each underwent field stimulation (FS) for a total of 20 s at 1-32 Hz, 1 ms and 80 V and was exposed to carbachol (100 micromol/L), ATP (2 mmol/L) and KCl (120 mmol/L). The tension was monitored continually using a polygraph and data stored digitally in a computer. The responses to each stimulus were determined as the maximum tension generated, maximum rate of tension generation and duration to a maximum response. The Ca2+- ATPase activity of the rat and rabbit bladder was determined. Bladder pressures were then predicted from the strip data using Laplace's law and compared with published values. RESULTS: Contractile responses (per unit tissue mass) of rat bladder strips were significantly greater than those of rabbit bladder strips at all frequencies of FS and to carbachol, KCl and ATP. The rate of contractile force generated by rat bladder strips in response to all stimuli were significantly greater than that generated by rabbit strips. Rabbit bladder strips took significantly longer to generate maximum tension than did rat bladder strips in response to pharmacological stimuli. In response to FS, rat strips took significantly longer than rabbit strips to generate maximum tension. Although the predicted rat bladder pressures were significantly greater than those for rabbit, the predicted pressures for both the rat and rabbit were significantly lower than the pressure responses of the isolated whole bladder model. The contractile data correlated well with the Ca2+-ATPase activity data; rat bladder had seven times the enzyme activity of rabbit bladder. CONCLUSION: Per unit mass, rat bladder is capable of generating more than five times the tension of rabbit bladder. Similarly, the rate of tension generation by rat bladder is three to five times greater than that by rabbit bladder. The duration to maximum tension generated in response to FS compared with pharmacological stimuli was affected by the inherent difference in the rate of contractile response to electrical activation compared with agents which diffuse through tissue, and by the difference in size between rat and rabbit bladder smooth muscle cells.

Adenosine Triphosphate↗

Subcellular distribution of free fatty acids, phospholipids, and endogenous lipase activity of rabbit urinary bladder smooth muscle and mucosa.

OBJECTIVES: The urinary bladder wall can be separated into two major compartments: the urothelium (mucosa) and the detrusor smooth muscle. Specific dysfunctions of both layers have been linked to ischemia, which may induce significant cellular and subcellular membrane damage via the activation of selective calcium dependent and independent hydrolytic enzymes. Preliminary to investigating changes in cell membrane composition induced by ischemia, we measured the free fatty acid (FFA) and phospholipid (PL) content of normal rabbit bladder muscle and mucosal cellular and subcellular membranes, and characterized the endogenous lipase activity. METHODS: Rabbit bladders were excised and the muscle and mucosal layers separated; each layer was homogenized, then fractionated by differential centrifugation. Endogenous lipase activity of the homogenates, and FFA and PL concentrations of the homogenates and subcellular fractions were measured. RESULTS: (1) The basal FFA concentration of the mucosal homogenates was 5 times that of the muscle homogenates. (2) The basal PL concentrations of the two tissues were similar. (3) Subcellular studies: FFA concentration was greatest in the mitochondrial fraction of both compartments. In the mucosa, PL concentration was significantly greater in the mitochondria and microsomes than in the other fractions; in the smooth muscle, the PL concentration was highest in the mitochondria. (4) The maximal endogenous lipase activity was 10 times higher in the mucosal homogenates than in the muscle homogenates. CONCLUSIONS: These results are consistent with those of previous studies which indicate that the mucosa is metabolically more active than the resting smooth muscle, which may cause the mucosa to be significantly more sensitive than the muscle to hypoxic/ischemic damage.

Animals↗

Effect of partial outflow obstruction on the distribution of free fatty acids and phospholipids in the rabbit bladder.

The urinary bladder is separated into two distinct components, the mucosal epithelium (urothelium) and the underlying detrusor smooth muscle. Specific bladder dysfunctions such as partial outlet obstruction may contribute to the breakdown and damage of cell membranes. The major component of cell membranes is phospholipids, and the release of free fatty acids (FFA) from membrane phospholipids is suggestive of degradative lipase activity. The current investigation is concerned with the effect of partial outlet obstruction on the subcellular distribution of free fatty acids and phospholipids (PL) in rabbit bladder muscle and mucosa. Partial outlet obstructions were surgically created in mature male New Zealand White rabbits by standard methodology. At 2 weeks following surgery, rabbits were euthanized and the bladders, removed and separated into smooth muscle and mucosa. Muscle and mucosa were homogenized and separated by differential centrifugation to obtain separate subcellular fractions including plasma membranes, mitochondria, microsomes, and cytosol. The homogenate and supernatant fraction, free of membranes, were also saved. The free-fatty-acid (FFA) and choline-containing phospholipid (PL) content and the rate of generation of FFA were quantitated using in vitro enzymatic colorimetric methods. Relative to controls there was a significant increase in the FFA content of the obstructed smooth muscle and an increase in the PL content of the obstructed mucosa. There was an increase in FFA content in the mitochondrial fraction and a decrease in the supernatant of the obstructed smooth muscle. The PL content was reduced in the obstructed smooth muscle microsomal and supernatant fractions and was increased in the supernatant fraction of the mucosa. Endogenous lipase activity among control bladders was more than 10-fold greater in mucosa than in muscle. The FFA generation of the smooth muscle was significantly reduced by partial outlet obstruction. In conclusion, partial outlet obstruction causes bladder dysfunction due to activation of enzymes that hydrolyze cellular and subcellular membranes. The increase in endogenous lipase activity and generation of FFA among obstructed bladders indicates that the pathological state affects the membrane structure needed for normal bladder function.

Animals↗