Lower urinary tract dysfunction (LUTd) represents a major health care problem with a high, unmet medical need. Design of additional therapies for LUTd requires precise tools to study bladder storage and voiding (dys)function in animal models. We developed videocystometry in mice, combining intravesical pressure measurements with high-speed fluoroscopy of the urinary tract. Videocystometry substantially outperforms current state-of-the-art methods to monitor the urine storage and voiding process, by enabling quantitative analysis of voiding efficiency, urethral flow, vesicoureteral reflux, and the relation between intravesical pressure and flow, in both anesthetized and awake, nonrestrained mice. Using videocystometry, we identified localized bladder wall micromotions correlated with different states of the filling/voiding cycle, revealed an acute effect of TRPV1 channel activation on voiding efficiency, and pinpointed the effects of urethane anesthesia on urine storage and urethral flow. Videocystometry has broad applications, ranging from the elucidation of molecular mechanisms of bladder control to drug development for LUTd.
Purpose: Prevention of myocardial injury is essential during cardiac surgery. Both crystalloid and blood cardioplegia are popular methods for myocardial protection. Most experimental studies have been in favor of blood cardioplegia. The objective of this study is to determine whether the use of warm blood cardioplegia (BCP) is superior to crystalloid cardioplegia (CCP) by means of myocardial injury markers and clinical outcome parameters. Materials and Methods: In a consecutive series of 293 patients, the first 150 received crystalloid cardioplegia, whereas the next 143 patients received blood cardioplegia. Postoperative myocardial injury was assessed by CTnI and CK-MB. Perioperative morbidity and mortality and clinical outcome parameters (need for inotropic support, ICU and hospital stay) were recorded. An unpaired student t-test was performed to analyse continuous postoperative variables relating to myocardial damage. The presence of possible confounders influencing the CTnI or CK-MB concentrations was tested using a student t-test for continuous variables, for categorical variables ANOVA was used. A final longitudinal model was created for CTnI and CK-MB. CTnI was analyzed by a mixed model with random intercept and slope. For all tests performed, statistical significance was 5%. Results: Both groups were well matched with respect to preoperative variables. No significant difference could be found in maximum postoperative levels of CTnI (8.8 ± 18.4 µg/l in BCP vs 9.6 ± 16.5 µg/l in CCP, p = 0.6455) or CK-MB (19.2 ± 31.0 µg/l in BCP vs 26.4 ± 41.5 µg/l in CCP, p = 0.1209). Nor was there any significant difference in other postoperative variables. Testing treatment effect over time proved only significant influence of the surgical intervention type on CTnI levels in time (p < 0.001). Conclusion: This study could not show significantly higher myocardial injury in the group of patients re
Understanding the lower urinary tract (LUT) and development of highly needed novel therapies to treat LUT disorders depends on accurate techniques to monitor LUT (dys)function in preclinical models. We recently developed videocystometry in rodents, which combines intravesical pressure measurements with X-ray-based fluoroscopy of the LUT, allowing the in vivo analysis of the process of urine storage and voiding with unprecedented detail. Videocystometry relies on the precise contrast-based determination of the bladder volume at high temporal resolution, which can readily be achieved in anesthetized or otherwise motion-restricted mice but not in awake and freely moving animals. To overcome this limitation, we developed a machine-learning method, in which we trained a neural network to automatically detect the bladder in fluoroscopic images, allowing the automatic analysis of bladder filling and voiding cycles based on large sets of time-lapse fluoroscopic images (>3 hours at 30 images/second) from behaving mice and in a non-invasive manner. With this approach, we found that urethane, an injectable anesthetic that is commonly used in preclinical urological research, has a profound, dose-dependent effect on urethral relaxation and voiding duration. Moreover, both in awake and in anaesthetized mice, the bladder capacity was decreased ~4-fold when cystometry was performed acutely after surgical implantation of a suprapubic catheter. Our findings provide a paradigm for the non-invasive, in vivo monitoring of a hollow organ in behaving animals and pinpoint important limitations of the current gold standard techniques to study the LUT in mice.
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