Differential bronchodilatory effects of terbutaline, diltiazem, and aminophylline in canine intraparenchymal airways.

OBJECTIVES: Intraparenchymal airways are involved in air flow regulation. Relaxation of intraparenchymal airways to volatile anesthetics varied by topographic location. This study was conducted to determine whether other bronchodilators (terbutaline, diltiazem, and aminophylline) relax bronchiolus to a greater degree than bronchus, as seen with volatile anesthetics. DESIGN: In vitro, controlled, randomized study. SETTING: Animal research laboratory. SUBJECTS: Adult dogs (n = 9). INTERVENTIONS: Proximal (outer diameter, 4-6 mm) and distal (outer diameter, 0.8-1.5 mm) airway rings of dogs were contracted in tissue baths with the effective concentration of acetylcholine that produces half the maximum response. Airway relaxant dose-response curves were constructed to measure isometric tension after administration of terbutaline (concentration range, 10(-8) to 10(-4) M), diltiazem (concentration range, 3 x 10(-7) to 1 x 10(-4) M), and aminophylline (concentration range, 10(-7) to 10(-4) M). MEASUREMENTS AND MAIN RESULTS: All three bronchodilators caused relaxation of the proximal and distal airways. At the maximum dose, diltiazem (maximum relaxation, 95%+/-2% [proximal], 94%+/-6% [distal]; p > .05) was the most efficacious, followed by terbutaline (maximum relaxation, 72%+/-13% [proximal], 55%+/-9% [distal]; p < .05) and aminophylline (maximum relaxation, 32%+/-10% [proximal], 35%+/-18% [distal]; p > .05. At the concentrations tested, they were equally efficacious. No significant differences in relaxation between proximal and distal airways were noted with diltiazem or aminophylline in the entire dose range. However, terbutaline relaxed the distal airway more than the proximal airway in the entire dose range. CONCLUSIONS: The results demonstrate that only terbutaline showed a differential airway relaxant effect between proximal and distal airways, as seen with volatile anesthetics.

The effect of angiotensin converting enzyme inhibition and angiotensin II receptor antagonism on obstructed rat bladder.

PURPOSE: Others have demonstrated that inhibition of angiotensin II production partially ameliorates obstructive changes in the neonatal rabbit bladder. We examined the effect of angiotensin II converting enzyme inhibition and receptor antagonism on the obstructed rat bladder. MATERIALS AND METHODS: Three groups of animals were investigated. Partial bladder neck obstruction was created in 23 rats by placing a 2-zero silk ligature around the vesicourethral junction. Eight rats were given untreated tap water, 9 were given water supplemented with 50 mg./kg. of the angiotensin-converting enzyme inhibitor captopril and 6 were given water with 30 mg./kg. of the angiotensin II subtype AT1 receptor antagonist losartan potassium. Eight unobstructed rats served as controls. After 2 weeks of partial outlet obstruction the animals were sacrificed and bladders were harvested. Routine histological evaluation and assays for total protein, deoxyribonucleic acid and collagen content were performed. RESULTS: Histological evaluation revealed that administration of captopril or losartan potassium resulted in a mild decrease in the degree of obstructive bladder changes. Biochemically neither captopril nor losartan potassium caused a significant decrease in the amount of total deoxyribonucleic acid, protein or collagen content per bladder compared to untreated obstructed bladders. CONCLUSIONS: In contrast to previous studies in neonatal rabbits, neither captopril nor losartan potassium significantly ameliorated the histological or biochemical features of partial bladder outlet obstruction in the rat. Further investigation is necessary into species specific differences to understand better the role that angiotensin II may have in mediating the bladder changes of experimentally induced obstruction.

Use of bladder stimulation in high risk patients.

PURPOSE: We evaluated whether intravesical bladder stimulation therapy is effective in improving bladder compliance in patients with myelomeningocele, neurogenic bladder and high risk urodynamic parameters. MATERIALS AND METHODS: We reviewed the charts of all patients treated with bladder stimulation therapy at our institution since 1984, and identified 7 with pretreatment high risk urodynamic findings (percent expected bladder capacity 60% or less and bladder capacity pressure 50 cm. water or greater). Urodynamic and clinical data were reviewed before and after therapy. RESULTS: Following bladder stimulation in 4 of the 7 patients percent expected bladder capacity substantially increased and bladder capacity pressure decreased to safe levels. Two patients had minimal increases in percent expected bladder capacity but bladder capacity pressure decreased to 50 cm. water or less. Overall percent expected bladder capacity increased from an average pretreatment value of 44% before to 65% after bladder stimulation (p < 0.05). Average bladder capacity pressure improved from 63.9 cm. water before to 32.3 cm. water after treatment (p < 0.05). Also, bladder compliance improved in all 7 patients to the point that bladder augmentation was not performed. CONCLUSIONS: Bladder stimulation is effective in improving bladder compliance in high risk patients and it may be a viable alternative to enterocystoplasty. Further long-term followup will be necessary to establish the longevity of this response.

Bladder stimulation therapy improves bladder compliance: results from a multi-institutional trial.

PURPOSE: We examined data from multiple institutions to determine whether intravesical bladder stimulation therapy is effective in improving bladder compliance by increasing bladder capacity and lowering bladder storage pressures. MATERIALS AND METHODS: The charts of 568 patients from 11 institutions were evaluated. Of the 568 patients 335 had adequate and accurate pretreatment and posttreatment urodynamic studies, and were included in this study. A total of 155 patients was from Children's Memorial Hospital, while the remaining 180 were from 10 other institutions. Bladder capacity and bladder capacity pressure were determined for each patient before and after therapy. RESULTS: Overall, 53% of patients had increased bladder capacity of 20% or greater after treatment (average increase 105 cc), which represents a 63% increase from pretreatment values. This increase occurred in an average of 1.9 years. Further analysis of this subset of patients revealed that in 90% intravesical storage pressures were decreased or maintained within a safe range (less than 40 cm. water). Evaluation of patients who did not respond to bladder stimulation with a 20% or greater increase in bladder capacity revealed that they had nearly normal bladder capacity before therapy. When the data on bladder capacity and bladder capacity pressure from Children's Memorial Hospital were compared to results from the 10 other institutions, there were no appreciable differences. CONCLUSIONS: Bladder stimulation is effective in increasing bladder capacity without significantly elevating storage pressure in a majority of patients. We conclude that this technique is safe and effective in improving bladder compliance, and that it is reproducible elsewhere.

Effects of acute hypothermia and beta-adrenergic receptor blockade on serum potassium concentration in rats.

BACKGROUND AND METHODS: We hypothesized that beta-adrenergic receptor blockade would result in an increase in serum potassium concentration in hypothermic rats given a potassium load compared to non-beta-blocked, hypothermic, potassium-loaded rats. To test this hypothesis, we investigated the interaction between body temperature and beta-adrenergic receptor blockade on serum potassium concentrations in ureter-ligated rats with and without potassium loading. To achieve this goal, we performed three experiments. In the first experiment, serum potassium concentrations were determined in 16 rats as they were continuously cooled from 37 degrees C to 22 degrees C. In the second experiment, 12 ureter-ligated rats were cooled to 31 degrees C, after which they were rewarmed to 37 degrees C. Serum potassium concentrations were determined before and after cooling and on rewarming. Twelve other ureter-ligated rats were cooled to 31 degrees C, then given a potassium load until their serum potassium concentrations returned to their baseline values, after which they were rewarmed to 37 degrees C. Serum potassium concentrations were determined before and after cooling, during the potassium infusion, and on rewarming. In the third experiment, 14 rats were pretreated with propranolol and 14 rats served as controls. Half of the rats in each of these two groups were kept at 37 degrees C and half were cooled to 25 degrees C. All rats were then given a 690-mumol potassium chloride infusion. Serum potassium concentrations were determined before and after the potassium infusion. RESULTS: The rats developed hypokalemia with cooling, which spontaneously resolved in the rats without supplementation on rewarming to 37 degrees C. The hypothermic hypokalemic rats that had their serum potassium concentrations corrected to normothermic status (2.93 +/- 0.17 mmol/L) had marked increases in serum potassium concentrations (4.22 +/- 0.15 mmol/L) on rewarming. In the normothermic rats, potassium loading after beta-adrenergic receptor blockade resulted in even higher serum potassium concentrations (5.65 +/- 0.36 mmol/L) compared with non-beta-blocked rats given equal potassium loads (4.6 +/- 0.4 mmol/L). However, in hypothermic (25 degrees C) rats given the same potassium load, there was no difference in serum potassium concentrations in beta-blocked (6.5 +/- 0.35 mmol/L) and non-beta-blocked rats (6.63 +/- 0.3 mmol/L). CONCLUSIONS: These results suggest that acute hypothermia causes a decrease in serum potassium, probably secondary to redistribution, which is reversible on rewarming. Supplementation of potassium during hypothermia can cause a significant increase in serum potassium concentration on rewarming. Blocking beta-adrenergic receptors with propranolol did not effect hypothermia-induced hypokalemia, suggesting that the beta-adrenergic mechanism may not be functional in hypothermia.