Increasing data from animal studies support the role of pelvic ischemia in Lower urinary tract symptoms (LUTS). Investigators currently perform vascular injury in iliac vessels of animals investigating lower urinary tract symptoms. However, in human, vascular obstruction is a chronic procedure allowing revascularization and adaptation of urinary bladder in hypoxia. Thus, results from animal models cannot be extrapolated to human population. Furthermore, clinical data from human studies regarding pelvic ischemia remain extremely scarce. 
We conducted a clinical study of patients with common iliac artery obstruction before and after surgical revascularization and in comparison with healthy controls, aiming at elucidating the association of vascular obstruction with LUTS and sexual function. Additionally, we examined established markers of pelvic ischemia (MDA, 8-OHdG) from animal studies in human urine samples from patients with vascular obstruction before and after surgical revascularization and in comparison with healthy controls. Finally, we investigated the curative role of surgery in patients with LUTS and vascular injury.

The study was approved by the Hospital Scientific Board and the local University Bioethics Committee. All participants were recruited following written informed consent. The current interim analysis included 15 patients with unilateral or bilateral common iliac artery obstruction (group A) who underwent revascularization by vascular surgeons and 9 controls without LUTS (IPSS≤7)(group B).  Exclusion criteria included history of prior lower urinary tract surgery, urinary tract malignancy, bladder lithiasis, neurogenic lower urinary tract dysfunction and use of micturition-affecting medication for a period of at least 6 months before entering the study.  All patients were examined at baseline and at 6 months post-revascularization. Participants filled the IPSS, OAB-q and IIEF questionnaires to evaluate their symptoms from the lower urinary tract and sexual function, and were submitted to uroflow (evaluated parameters: post-void residual - PVR, max. flow rate - Qmax, average flow rate - Qave) and ultrasound examination. Additionally, patients with IPSS score>7 (group A1, n=6) underwent urodynamic study before and after intervention.  Age, somatometrics (height, weight, waist circumference, BMI), social factors (smoking, alcohol consumption, weekly hours of exercise), medical history (diabetes mellitus, hypertension) served as independent variables. Additionally, urinalysis and blood tests including PSA levels, triglycerides, cholesterol, LDL, HDL, urea and creatinine were performed at baseline. 
Levels of malondialdehyde (MDA) and 8-OHdG representing lipid peroxidation/depicted levels of pelvic ischemia and oxidative stress respectively were measured in urine specimens with ELISA (ab201734, Abcam). Free-void urine specimens were collected at baseline and at the 6-month post-intervention follow-up. Specimens were preserved  with urine preservative single dose, NORGEN BIOTEK CORP, Canada.

There were no differences in age (62±7 vs 60±7 years) and prostate size (36±12cm3 vs 35±14cm3) between the patients’ and controls’ groups. 
There were statistically significant differences between patients and controls in ΙPSS-total score (group A:8.2±6.6 vs group Β:1.2±1.2, p<0.001), IPSS-Storage (p=0.023), IPSS-Voiding (p=0.004), OAB-total (p=0.005), OAB-bother (p=0.011), OAB-concern (p=0.023), OAB-coping (p=0.010) και IIEF-desire (p=0.046). Moreover, micturition time and PVR differed significantly between the groups (group A: Mn 53±30 vs group B: Mn 30±12, p=0.044 and group A: Md 35 IQR 106 vs group B: Md 4 IQR 27.3, p=0.035 respectively). After revascularization, there was significant improvement in ΙPSS-total score (before:15±5.5 vs after :8.8±5.2, p=0.027), IPSS-Voiding (9±5.5 vs 5.1±5, p=0.027), IPSS-Storage (6.8±4.4 vs 3.6±3.6, p=0.041) in patients with baseline IPSS>7 (subgroup A1) and in sexual desire of all patients (group A, p=0.019). 
Levels of MDA (group A- Md:71 IQR:220, group B- Md:125 IQR: 203, post operation- Md:81 IQR:264) correlated negatively and significantly with ΙPSS-total (rho: -0.853, p=0.003) and IPSS-Storage (rho: -0.751, p=0.020) in healthy individuals. Baseline levels of 8-OHdG (group A Mn: 56.88±27.67, group B Mn:70±36.29, post-operative Mn:66.24±37.57) related significantly with MDA (p:0.045, rho:0.413), hours of weekly exercise (p:0.024, rho:0.458) and cholesterol levels (p:0.02, rho:0.472). There were also statistically significant differences (p:0.047) in 8-OHdG levels of diabetics (Mn:47.71±34.42) and non-diabetic (Mn:64.89±18.98) patients. Reduction of 8-OHdG levels after intervention associated strongly and positively with reduction of MDA levels (p:0.023, rho:0.621).

Obstruction of iliac vessels is considered a predisposing factor of pelvic ischemia and lower urinary tract symptoms. However, current knowledge derives from animal models and cannot be applied to human. Our study results suggest that patients with unilateral or bilateral obstruction of common iliac artery suffered from more severe LUTS compared to healthy individuals, confirming current animal studies. Additionally, surgical revascularization could improve LUTS in patients with moderate to severe symptoms (IPSS>7). However, the sample size was small and the follow-up short for robust results. Regarding the role of urine biomarkers of pelvic ischemia, the clinical associations found for MDA and 8-OHdG are probably also affected by the small sample size and further research is suggested.

Interim results of our study suggests that chronic iliac artery obstruction could be associated with LUTS in the human. Surgical revascularization could improve LUTS in patients with moderate-to-severe LUTS (IPSS>7). Larger studies are needed to explore whether surgical revascularization could be a possible future treatment in patients with moderate/severe LUTS and unilateral or bilateral obstruction of iliac vessels. Clinical associations of molecular biomarkers of pelvic ischemia in urine were noted mostly at baseline. Their clinical value needs further study.