Combination of Doxazosin and Sildenafil Exerts an Additive Relaxing Effect Compared with Each Compound Alone on Human Cavernosal and Prostatic Tissue

IntroductionPhosphodiesterase 5 inhibitors (PDE5) such as sildenafil are first-line treatment for erectile dysfunction (ED). Alpha1 (α1)-adrenoceptor antagonists such as doxazosin are indicated for the treatment of patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). ED and LUTS/BPH are conditions that are often associated. Accordingly, α1-adrenoceptor antagonists and PDE5 inhibitors will be often prescribed in real life setting together.AimTo evaluate the effects of the combination of sildenafil and doxazosin on human cavernosal and prostatic tissue.MethodsProstatic and erectile tissues were obtained from nine to 12 patients, respectively. Patients underwent cystoprostatectomy for infiltrating bladder cancer or penile surgery for penile implant, congenital curvature or Peyronie's disease.Main Outcome MeasuresIn organ baths, prostatic and cavernosal strips were submitted to either concentration-response curves (CRC) to phenylephrine (Phe) or norepinephrine (NE), respectively, in presence of vehicle, sildenafil (10^?6 M, 10^?5 M), doxazosin (10^?8 M, 3.10^?8 M, or 10^?7 M), or a combination of both. Continuous electrical field stimulation (EFS; 32 Hz, 5 ms, 5 seconds, 300 mA) was performed on prostatic strips which were incubated with sildenafil 10^?6 M or vehicle before the successive addition of doxazosin (10^?7 M, 10^?6 M) or vehicle. Cavernosal strips were pre-incubated with doxazosin (10^?9 M, 10^?8 M) or vehicle, then CRC to sildenafil were constructed on NE (3.10^?6 M) precontracted cavernosal strips.ResultsCombination of sildenafil and doxazosin exerted a greater relaxing effect on CRC to Phe or NE compared with each compound alone in both tissues. Sildenafil significantly enhanced the relaxing effect of doxazosin on EFS-induced contractions in prostatic strips. Doxazosin significantly increased the ability of sildenafil to inhibit NE-induced contractions in cavernosal strips.ConclusionsSildenafil and doxazosin reduced adrenergic tone of prostatic and cavernosal smooth muscle and their combination provided a significant benefit when targeting relaxation of both tissues. These experiments provide support for further clinical evaluation of the sildenafil and doxazosin combination in ED patients with LUTS/BPH. Oger S, Behr-Roussel D, Gorny D, Lecoz O, Lebret T, Denoux Y, Faix A, Leriche A, Wayman C, Alexandre L, and Giuliano F. Combination of doxazosin and sildenafil exerts an additive relaxing effect compared with each compound alone on human cavernosal and prostatic tissue. J Sex Med 2009;6:836–847.     

Atrial flutter termination by overdrive transesophageal pacing and the facilitating effect of oral propafenone

Transesophageal overdrive atrial pacing is effective and safe for atrial flutter termination. The influence of antiarrhythmic drug therapy on this procedure is controversial. In this study, we investigated whether oral propafenone may facilitate this procedure. Thirty patients with type I atrial flutter were randomized into 2 groups in which transesophageal pacing was attempted: group A, without treatment; and group B, after oral administration of propafenone 600 mg. Transesophageal pacing was effective in interrupting atrial flutter in 53% of patients (8 of 15) in group A and in 87% of patients (13 of 15) in group B. A significant lengthening of the flutter cycle was observed with respect to the baseline in patients given propafenone (261 ± 23 vs 217 ± 25, p < 0.01). Sinus rhythm resumed at a shorter paced cycle in group A patients (166 ± 13 vs 187 ± 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture was significantly lower in group A (20.5 ± 0.2 vs 23.3 ± 1.2, p < 0.01). In no patient was the threshold for atrial capture higher than the pain threshold. We did not observe abrupt enhancement of atrioventricular conduction. We conclude that propafenone is effective and safe when used with transesophageal pacing in the termination of atrial flutter. The slowing effect of the drug on intraatrial conduction and the possible stabilizing effect on the reentry circuit appear to be outweighed by the positive effect of propafenone on the excitable gap of the circuit, facilitating its capture and accounting for the beneficial effect of the drug on arrhythmia termination.     

Forced alignment of mesenchymal stem cells undergoing cardiomyogenic differentiation affects functional integration with cardiomyocyte cultures

Alignment of cardiomyocytes (CMCs) contributes to the anisotropic (direction-related) tissue structure of the heart, thereby facilitating efficient electrical and mechanical activation of the ventricles. This study aimed to investigate the effects of forced alignment of stem cells during cardiomyogenic differentiation on their functional integration with CMC cultures. Labeled neonatal rat (nr) mesenchymal stem cells (nrMSCs) were allowed to differentiate into functional heart muscle cells in different cell-alignment patterns during 10 days of coculture with nrCMCs. Development of functional cellular properties was assessed by measuring impulse transmission across these stem cells between 2 adjacent nrCMC fields, cultured onto microelectrode arrays and previously separated by a laser-dissected channel (230+/-10 microm) for nrMSC transplantation. Coatings in these channels were microabraded in a direction (1) parallel or (2) perpendicular to the channel or were (3) left unabraded to establish different cell patterns. Application of cells onto microabraded coatings resulted in anisotropic cell alignment within the channel. Application on unabraded coatings resulted in isotropic (random) alignment. After coculture, conduction across seeded nrMSCs occurred from day 1 (perpendicular and isotropic) or day 6 (parallel) onward. Conduction velocity across nrMSCs at day 10 was highest in the perpendicular (11+/-0.9 cm/sec; n=12), intermediate in the isotropic (7.1+/-1 cm/sec; n=11) and lowest in the parallel configuration (4.9+/-1 cm/sec; n=11) (P<0.01). nrCMCs and fibroblasts served as positive and negative control, respectively. Also, immunocytochemical analysis showed alignment-dependent increases in connexin 43 expression. In conclusion, forced alignment of nrMSCs undergoing cardiomyogenic differentiation affects the time course and degree of functional integration with surrounding cardiac tissue.     

Ileal patch duodenoplasty after right colectomy extended to the duodenal wall

After radical resection of cancer of the right colonic flexure, a parietal defect can be created in case of duodenal invasion. In this paper the authors describe an "easy and safe" duodenoplasty surgical technique using an ileal patch.     

Usefulness of ultrasonography in predicting pleural effusions > 500 mL in patients receiving mechanical ventilation

STUDY OBJECTIVE: To assess the accuracy of chest ultrasonography in predicting pleural effusions > 500 mL in patients receiving mechanical ventilation. DESIGN: Prospective study. SETTING: Surgical and medical ICU in a teaching hospital. PATIENTS: Forty-four patients receiving mechanical ventilation with indications of chest drainage of a nonloculated pleural effusion. INTERVENTIONS: Diagnosis of pleural effusion was based on clinical examination and chest radiography. Chest drainage was indicated when considered as potentially useful for the patient (hypoxemia and/or weaning failure). Sonograms were performed before drainage at the bedside, in the supine position, and measurements were performed at the end of expiration. Effusions were classified as > 500 mL or < or = 500 mL according to the drained volume. MEASUREMENTS AND RESULTS: The drained volume ranged from 100 to 1,800 mL (mean, 730 +/- 440 mL [+/- SD]). The distance between the lung and posterior chest wall at the lung base (PLDbase) and the distance between the lung and posterior chest wall at the fifth intercostal space (PLD5) were significantly correlated with the drained volume (PLDbase, r = 0.68, p < 0.001; PLD5, r = 0.56, p < 0.001). A PLDbase > 5 cm predicted a drained volume > 500 mL with a sensitivity of 83%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 82%. Interobserver and intraobserver percentages of error were, respectively, 7 +/- 6% and 9 +/- 6% for PLDbase, and 6 +/- 5% and 8 +/- 5% for PLD5. The PaO2/fraction of inspired oxygen ratio significantly increased after chest drainage in patients with collected volumes > 500 mL (p < 0.01). CONCLUSIONS: Bedside pleural ultrasonography accurately predicted a nonloculated pleural effusion > 500 mL in patients receiving mechanical ventilation using simple and reproducible measurements.     

Prognostic value of aerobic capacity and exercise oxygen pulse in postaortic dissection patients

BackgroundAlthough recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient''s physical rehabilitation and assess their cardiovascular prognosis.DesignWe aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed‐up after acute aortic dissection.MethodsPatients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow‐up was done after CPET for new aortic event and major cardio‐vascular events (MCE) not directly related to the aorta.ResultsAmong the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22‐1.84) mlO2/beat, that is, 97 (83–113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow‐up of 39(20‐51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (<85% of predicted value) was independently predictive of aortic event recurrence, while low peak oxygen uptake (<70% of predicted value) was an independent predictor of MCE occurrence.ConclusionCPET is safe in postaortic dissection patients should be used to not only to personalize exercise rehabilitation, but also to identify those patients with the highest risk for new aortic events and MCE not directly related to aorta.