Iliac Artery Blood Flow Research Articles

Midterm Results of a Surgeon-Modified Device to Preserve the Flow of the Internal Iliac Artery During Endovascular Repair of Aneurysm: Single-Center Experiences

During endovascular aneurysm repair (EVAR), commercial iliac branch devices (IBDs) have become an inescapable alternative for preserving antegrade internal iliac artery (IIA) blood flow. Due to the different morphological features of aneurysms, commercial IBDs may not be suitable for all patients. Reported experience with the implantation of the new surgeon-modified IBD (sm IBD) is limited. This investigation describes the indications, efficacy, and safety of the sm IBD. Data from consecutive elective implantations of IBDs in patients between March 2011 and May 2021 in a single center were incorporated. The sm IBDs were indicated in patients with common iliac artery aneurysms (CIAAs) and with a challenging anatomy and in those patients with or without abdominal aortic aneurysm (AAA). Fifteen patients (15 male, mean age 67.6±7.9years) were included. Fifteen sm IBDs were implanted in 1 procedure (100%). Fourteen (93.3%) patients had simultaneous endovascular aneurysm repair (EVAR) and 1 (6.7%) patient previously had a bilateral CIAAs repair by EVAR. The mean common iliac artery (CIA) diameter was 36.6±12.5mm. Technical success was obtained in all patients (100%). The median operation time was 189.7±78.6min, with a median fluoroscopy time of 45.3±15.9min. Axillary artery access was used in 11 (73.3%) procedures. The mean total hospital stay was 5.6±2.8days, and the postoperative follow-up was 35.4months (range 2-120). The estimated IIA bridge stent patency at 1year after operation was 100% and 85.7%±13.2% 5years postoperatively. One (6.7%) IIA branch was occluded, and this patient remained asymptomatic. One patient (6.7%) needed reintervention, and another (6.7%) patient had type II leakage, which is currently under close surveillance. Using an IBD to maintain the pelvic blood flow is an effective and feasible intravascular technique, especially for patients with an abnormal iliac artery anatomy. This novel technique has similar midterm procedural success rate compared to the use of commercial IBDs. Therefore, these devices are more suitable for patients with certain anatomic challenges and can be used as an alternative treatment.

Sleep your baby supine, but mums-to-be should sleep on their side.

Sleep your baby supine, but mums-to-be should sleep on their side.

The effects of maternal position, in late gestation pregnancy, on placental blood flow and oxygenation: an MRI study.

Maternal supine sleep position in late pregnancy is associated with an increased risk of stillbirth. Maternal supine position in late pregnancy reduces maternal cardiac output and uterine blood flow. Using MRI, this study shows that compared to the left lateral position, maternal supine position in late pregnancy is associated with reduced utero-placental blood flow and oxygen transfer across the placenta with an average 6.2% reduction in oxygen delivery to the fetus and an average 11% reduction in fetal umbilical venous blood flow. Maternal sleep position in late gestation is associated with an increased risk of stillbirth, though the pathophysiological reasons for this are unclear. Studies using magnetic resonance imaging (MRI) have shown that compared with lateral positions, lying supine causes a reduction in cardiac output, reduced abdominal aortic blood flow and reduced vena caval flow which is only partially compensated for by increased flow in the azygos venous system. Using functional MRI techniques, including an acquisition termed diffusion-relaxation combined imaging of the placenta (DECIDE), which combines diffusion weighted imaging and T2 relaxometry, blood flow and oxygen transfer were estimated in the maternal, fetal and placental compartments when subjects were scanned both supine and in left lateral positions. In late gestation pregnancy, lying supine caused a 23.7% (P<0.0001) reduction in total internal iliac arterial blood flow to the uterus. In addition, lying in the supine position caused a 6.2% (P=0.038) reduction in oxygen movement across the placenta. The reductions in oxygen transfer to the fetus, termed delivery flux, of 11.2% (P=0.0597) and in fetal oxygen saturation of 4.4% (P=0.0793) did not reach statistical significance. It is concluded that even in healthy late gestation pregnancy, maternal position significantly affects oxygen transfer across the placenta and may in part provide an explanation for late stillbirth in vulnerable fetuses.

Arterial Responses in Periparturient Beef Cows Following a 9-Week Exposure to Ergot (Claviceps purpurea) in Feed.

Ergot alkaloids are vasoconstrictors frequently detected in low concentrations in livestock feed. The Canadian Food Inspection Agency permits up to 3,000 μg ergot alkaloids per kg cattle feed. The objective of this study was to examine the effects of feeding low concentrations of ergot alkaloids over 9-weeks on vascular dynamics in the caudal and internal iliac arteries of beef cows. A relationship between ergot alkaloid concentration in feed and hemodynamic changes in the caudal and internal iliac arteries was hypothesized. Periparturient beef cows were randomized into four groups and group fed mixed rations containing <15 μg ergot alkaloids per kg of dry matter intake (Control, n = 9), 48 μg/kg (Low, n = 9), 201 μg/kg (Medium, n = 8), and 822 μg/kg (High, n = 6). Three experimental periods comprised the study: pre-treatment (2 weeks), treatment (9 weeks), and post-treatment (3 weeks). B-mode and Doppler ultrasonography was performed weekly to measure hemodynamic endpoints. Plasma prolactin concentrations and rectal temperatures were measured weekly. Caudal artery diameter decreased (Treatment*Experimental Period i.e., Tx*EP, p < 0.001) by 14% in the High group during the treatment period. Reductions (Tx*EP, p < 0.001) in caudal artery blood flow (37%, 29%) and blood volume per pulse (29%, 11%) were recorded during the treatment period in the High and Medium groups. Internal iliac artery diameter and blood flow decreased (Tx*EP, p ≤ 0.004) by 13% and 40% during the treatment period in the Medium group. Moderate reductions (Tx*EP, p ≤ 0.042; 12–25%) in the mean blood velocity during the treatment and post-treatment periods and decreases (Tx*EP, p ≤ 0.01; 12–17%) in the peak systolic velocity of both arteries during the post-treatment period were also detected. Prolactin did not change in any group during the treatment period (p = 0.462). Rectal temperatures were within the normal physiological range for beef cows. In conclusion, we documented moderate vasoconstriction in the caudal artery and the internal iliac artery in cows fed 201–822 μg ergot alkaloids per kg of dry matter intake for 9-week period near parturition. The pattern of alterations was similar between the caudal and internal iliac arteries. Results of this study suggest that feeding up to 822 μg/kg produce reversible pharmacological changes in beef cow vasculature and warrant reconsideration of current regulations for cattle.

Surgical Complications after Open Abdominal Aortic Aneurysm Repair: Intestinal Ischemia, Buttock Claudication and Sexual Dysfunction

While surgical treatment for abdominal aortic aneurysm (AAA) is a standard operation, prevention of complication is important. Intestinal ischemia of the sigmoid colon and/or rectum after AAA surgery is severe and has a high mortality rate although occurrence frequency is low. The most important thing to prevent is the preoperative and intraoperative evaluation of the left hemicolon and rectal circulation. Measurement of inferior mesenteric artery stump pressure is also useful. From the viewpoint of prevention of buttock claudication, it is desirable that internal iliac artery (IIA) blood flow is preserved, but aggressive IIA reconstruction adaptation is considered to be low. For erectile function, it is important that the antegrade blood flow from the IIA to the internal pudendal artery on at least one side is preserved or reconstructed. To prevent retrograde ejaculation, it is important to preserve the superior hypogastric plexus and one side of the lumbar splanchnic nerve, and the hypogastric nerve. Understanding and mastering local anatomy and pathophysiology is important in preventing complications, and we must also remember that we always keep watchful surgical operations in mind in order to prevent tissue damage. (This is a translation of Jpn J Vasc Surg 2019; 28: 99–103.)

Is bladder blood flow an etiologic factor for the bladder pain syndrome?

Bladder pain syndrome (BPS) is a complex disease which causes cognitive, behavioral, sexual, and emotional problems. Vascular factors related to bladder blood supply may be one of the etiologic cause of BPS. This study aims to investigate the bladder blood flow and internal iliac artery resistive indices of patients with BPS. A total of 30 female patients with the diagnosis of BPS and 30 female as control group were enrolled in the study. Bilateral internal iliac arterial blood flow distal to uterine arteries were examined as the primary source of vesical arterial blood supply. Peak systolic velocities, end diastolic velocities, resistive indices, and flow volumes of internal iliac arteries were measured by color Doppler ultrasonography in a single-blind fashion. The blood flows volume of the right and left internal iliac arteries during empty and full bladder were significantly lower at BPS group compared with control (P < 0.05). Although the difference was not significant, the mean resistive index of right and left internal iliac arteries were lower at the control group ( P > 0.05). Aging decreased the bladder blood volume and both BPS and control group internal iliac artery blood volume decreased by aging. The decrease was more significant at the control group, but the internal iliac artery blood volume was still lower at patients with BPS compared with the control group. Arterial blood flow of bladder was lower at patients with BPS compared with the control group. The decrease in the vascular supply of bladder might be one of the related factors for the BPS etiology.

Blood flow changes in pelvic vessels associated with the application of an abdominal compression belt in healthy postpartum women

Postpartum haemorrhage (PPH) accounts for a high proportion of maternal mortality and morbidity throughout the world. A uterine compression belt which has been developed recently represents a very low tech, low cost solution in managing postpartum haemorrhage. To evaluate the blood flow changes in pelvic vessels following application of the postpartum haemorrhage compression belt (Laerdal Global Health, Stavanger, Norway). The sample included healthy postpartum women within 6 hours of vaginal delivery. The study was performed at Teaching Hospital, Ragama, Sri Lanka. PPH compression belt was applied on the lower abdomen in a supine position with a slight lateral tilt. Patient’s pulse, blood pressure and Doppler indices (RI, PI and PFV) of the uterine, internal iliac and femoral arteries were measured using transabdominal Doppler ultrasonography. Lower limb oxygen saturation was also measured. Measurements were obtained by connecting the subjects to a multimonitor throughout the study period of 20 minutes. Median RI, PI and PFV was calculated and comparisons were made between the baseline and after belt application at 10 and 20 minutes. A total of 20 healthy women were included and the mean time from delivery to study inclusion was 2.5 (range 0.5–5.0) hours. There were no adverse outcomes or altered vital signs noted among participants. Overall there were no significant changes in the internal iliac, uterine and femoral artery blood flow after application of the compression belt. There were no significant changes in the internal iliac, uterine and femoral artery blood flow after application of the compression belt. This preliminary study only shows that the application of the PPH compression belt has no apparent adverse changes in the iliac, uterine and femoral artery blood flow in postpartum mothers.

P13.06: Ultrasound evaluation of saftly of postpartum hemorrhage (PPH) compression belt in reduction of uterine, internal iliac and femoral artery blood flow in healthy postpartum women

P13.06: Ultrasound evaluation of saftly of postpartum hemorrhage (PPH) compression belt in reduction of uterine, internal iliac and femoral artery blood flow in healthy postpartum women

Axillary Artery Deployment of Endovascular Aortic Repair Iliac Limb for Preservation of Internal Iliac Artery Blood Flow

The axillary artery approach has been used for access for complex endovascular aortic procedures such as thoracic endovascular aortic repair with poor anatomy for traditional deployment as well as for fenestrated and branched abdominal aortic endografts. We report the first case of an iliac graft limb deployment through the axillary artery during an endovascular aortic repair for maintenance of anterograde internal iliac flow in a patient with a symptomatic abdominal aortic aneurysm and chronic occlusion of both the external iliac and common femoral arteries.

MP8-08 PROLONGED ISCHEMIA MEDIATES OVERACTIVE BLADDER TRANSITION TO UNDERACTIVE BLADDER

INTRODUCTION AND OBJECTIVES: Underactive bladder (UB) is a clinical challenge both in terms of accurate diagnosis and effective treatment. The etiology of UB remains unknown. Growing evidence suggests that chronic ischemia may contribute to bladder structural damage and dysfunction. We examined voiding behavior, cystometrograms (CMG), and tissue samples after short-term (8 weeks) and long-term (16 weeks) bladder ischemia. METHODS: Male Sprague-Dawley rats were assigned to treatment, sham,andage-matchedcontrol groups. In the treatedgroup, vascular lesions were introduced to create bilateral iliac artery atherosclerosis and chronic bladder ischemia. Subgroups underwent metabolic cage studies, hemodynamicmeasurements, andCMGat 8weeks and 16weeks after the induction of bladder ischemia. Tissues were processed for analysis. RESULTS: Iliac artery and bladder blood flow decreased in the treated group. At 8 weeks, 60% of treated group developed moderate bladder ischemia (MBI) and 40%had severe bladder ischemia (SBI). At 16 weeks, 30% of treated group had MBI and 70% had SBI. Metabolic cage studies showed increased micturition frequency (MF) and decreased voided volume (VV) in short-term MBI and SBI and long-term MBI. Longterm SBI decreased MF but did not alter VV. CMG showed marked fluctuations in intravesical pressure in MBI and decreased contractile activity in SBI. With filling, pre-micturition pressure increased and bladder compliance decreased in short-termMBI and SBI and in long-termMBI. In long-term SBI, pre-micturition pressure and bladder compliance decreased and residual volume increased. Markers of free radical injury and oxidative stress were present in MBI and SBI. Organ bath showed hypersensitivity to contractile stimuli in MBI and impaired contractile reactivity in SBI. Western blot showed significant upregulation of muscarinic M2 receptor in both short-term and long-term MBI and upreguation of M1 and downregulation of M3 in long-term SBI. TEM showed mitochondrial structural damage in MBI and decrease mitochondrial density in SBI. CONCLUSIONS: Structural and functional consequences of bladder ischemia depend on the severity and duration of arterial insufficiency. Short-term ischemia induced overactivity regardless of severity, while the effects of long-term ischemia are severity-dependent. Prolonged severe ischemia leads to changes consistent with UB. Longterm SBI appears to mediate the transition to underactivity via mechanisms involving oxidative stress, muscarinic receptors, mitochondrial energy production, and loss of contractile activity.

Valve-Like and Protruding Calcified Intimal Flap Complicating Common Iliac Arteries Kissing Stenting.

Endovascular therapy for iliac artery chronic total occlusions is nowadays associated with low rates of procedure-related complications and improved clinical outcomes, and it is predominantly used as first-line therapy prior to aortobifemoral bypass grafting. Herein, we describe the case of a patient presenting with an ischemic left foot digit ulcer and suffering complex aortoiliac lesions, who received common iliac arteries kissing stents, illustrating at final antegrade and retrograde angiograms the early recognition of a blood flow obstructing valve-like calcified intimal flap protruding through the stent struts, which was obstructing antegrade but not retrograde unilateral iliac arterial axis blood flow. The problem was resolved by reconstructing the aortic bifurcation at a more proximal level. Completion angiogram verified normal patency of aorta and iliac vessels. Additionally, a severe left femoral bifurcation stenosis was also corrected by endarterectomy-arterioplasty with a bovine patch. Postintervention ankle brachial pressure indices were significantly improved. At the 6-month and 2-year follow-up, normal peripheral pulses were still reported without intermittent claudication suggesting the durability of the procedure. Through stent-protruding calcified intimal flap, is a very rare, but existing source of antegrade blood flow obstruction after common iliac arteries kissing stents.

Differential changes in vascular mRNA levels between rat iliac and renal arteries produced by cessation of voluntary running

Early vascular changes at the molecular level caused by adoption of a sedentary lifestyle are incompletely characterized. Herein, we employed the rodent wheel-lock model to identify mRNAs in the arterial wall that are responsive to the acute transition from higher to lower levels of daily physical activity. Specifically, we evaluated whether short-term cessation of voluntary wheel running alters vascular mRNA levels in rat conduit arteries previously reported to have marked increases (i.e. iliac artery) versus marked decreases (i.e. renal artery) in blood flow during running. We used young female Wistar rats with free access to voluntary running wheels. Following 23 days of voluntary running (average distance of ∼15 km per night; ∼4.4 h per night), rats in one group were rapidly transitioned to a sedentary state by locking the wheels for 7 days (n = 9; wheel-lock 7 day rats) or remained active in a second group for an additional 7 days (n = 9; wheel-lock 0 day rats). Real-time PCR was conducted on total RNA isolated from iliac and renal arteries to evaluate expression of 25 pro-atherogenic and anti-atherogenic genes. Compared with the iliac arteries of wheel-lock 0 day rats, iliac arteries of wheel-lock 7 day rats exhibited increased expression of TNFR1 (+19%), ET1 (+59%) and LOX-1 (+31%; all P < 0.05). Moreover, compared with renal arteries of wheel-lock 0 day rats, renal arteries of wheel-lock 7 day rats exhibited decreased expression of ETb (-23%), p47phox (-32%) and p67phox (-19%; all P < 0.05). These data demonstrate that cessation of voluntary wheel running for 7 days produces modest, but differential changes in mRNA levels between the iliac and renal arteries of healthy rats. This heterogeneous influence of short-term physical inactivity could be attributed to the distinct alteration in haemodynamic forces between arteries.

Effects of age and hypertension on α1-adrenoceptors in the major source arteries of the rat bladder and penis

α(1)-Adrenoceptors regulate blood pressure, regional vascular resistance and tissue blood flow. As aging and hypertension may impact pelvic arterial blood flow resulting in bladder and penile dysfunction, we investigated effects of age and hypertension on α(1)-adrenoceptors in the major source arteries of the rat bladder and penis. Using radioligand receptor binding, real-time reverse transcription-polymerase chain reaction (RT-PCR) and fluorescent microsphere infusion techniques, we compared 3 and 22-month-old male Fischer rats, and male normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Twenty-two-month-old rats and SHRs had significantly higher total α(1)-adrenoceptor density in the internal iliac artery and lower blood flow to the bladder and penis than 3-month-old and WKY rats, respectively. RT-PCR data showed an age and hypertension related increase in the expression of α(1B)-adrenoceptor mRNA in the internal iliac, vesical and internal pudendal arteries and a switch from α(1A) predominance in 3-month-old and WKY rats to α(1B)>α(1A) in 22-month-old rats and SHRs. Our data indicate the presence of age and hypertension related alterations in vascular α(1)-adrenoceptor subtype distribution and in blood flow to the rat bladder and penis. These findings suggest that pharmacological blockade of the vascular α(1B)-adrenoceptor, which could increase pelvic blood flow, may contribute to the improvement of bladder and penile dysfunctions in animal models for aging and hypertension.

Effects of age and hypertension on α1‐adrenoceptors in the major source arteries of the rat bladder and penis

As aging and hypertension may impact pelvic arterial blood flow resulting in bladder and penile dysfunction, we investigated effects of age and hypertension on α1‐adrenoceptors in the major source arteries of the rat bladder and penis. Using radioligand receptor binding, real‐time RT‐PCR and fluorescent microsphere infusion techniques, we compared 3 and 22‐month‐old male Fischer rats, and male normotensive Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Twenty‐two‐month‐old rats and SHRs had significantly higher total α1‐adrenoceptor density in the internal iliac artery and lower blood flow to the bladder and penis than 3‐month‐old and WKY rats, respectively. RT‐PCR data showed an age and hypertension related increase in the expression of α1B‐adrenoceptor mRNA in the internal iliac, vesical and internal pudendal arteries and a switch from α1A predominance in 3‐month‐old and WKY rats to α1B&gt;α1A in 22‐month‐old rats and SHRs. These findings suggest that pharmacological blockade of the vascular α1B‐adrenoceptor, which could increase pelvic blood flow, may contribute to the improvement of bladder and penile dysfunction in animal models for aging and hypertension. Supported by KAKENHI 21791511, Grant‐in‐Aid for Young Scientists (B) provided by the Ministry of Education, Culture, Sports, Science and Technology of Japan.

High-end arteriolar resistance limits uterine artery blood flow and restricts fetal growth in preeclampsia and gestational hypertension at high altitude

The reduction in infant birth weight and increased frequency of preeclampsia (PE) in high-altitude residents have been attributed to greater placental hypoxia, smaller uterine artery (UA) diameter, and lower UA blood flow (Q(UA)). This cross-sectional case-control study determined UA, common iliac (CI), and external iliac (EI) arterial blood flow in Andeans residing at 3,600-4,100 m, who were either nonpregnant (NP, n = 23), or experiencing normotensive pregnancies (NORM; n = 155), preeclampsia (PE, n = 20), or gestational hypertension (GH, n = 12). Pregnancy enlarged UA diameter to ~0.62 cm in all groups, but indices of end-arteriolar vascular resistance were higher in PE or GH than in NORM. Q(UA) was lower in early-onset (≤34 wk) PE or GH than in NORM, but was normal in late-onset (>34 wk) illness. Left Q(UA) was consistently greater than right in NORM, but the pattern reversed in PE. Although Q(CI) and Q(EI) were higher in PE and GH than NORM, the fraction of Q(CI) distributed to the UA was reduced 2- to 3-fold. Women with early-onset PE delivered preterm, and 43% had stillborn small for gestational age (SGA) babies. Those with GH and late-onset PE delivered at term but had higher frequencies of SGA babies (GH=50%, PE=46% vs. NORM=15%, both P < 0.01). Birth weight was strongly associated with reduced Q(UA) (R(2) = 0.80, P < 0.01), as were disease severity and adverse fetal outcomes. We concluded that high end-arteriolar resistance, not smaller UA diameter, limited Q(UA) and restricted fetal growth in PE and GH. These are, to our knowledge, the first quantitative measurements of Q(UA) and pelvic blood flow in early- vs. late-onset PE in high-altitude residents.

Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries

Restenosis resulting from neointimal hyperplasia (NH) limits the effectiveness of intravascular stents. Rates of restenosis vary with stent geometry, but whether stents affect spatial and temporal distributions of wall shear stress (WSS) in vivo is unknown. We tested the hypothesis that alterations in spatial WSS after stent implantation predict sites of NH in rabbit iliac arteries. Antegrade iliac artery stent implantation was performed under angiography, and blood flow was measured before casting 14 or 21 days after implantation. Iliac artery blood flow domains were obtained from three-dimensional microfocal X-ray computed tomography imaging and reconstruction of the arterial casts. Indexes of WSS were determined using three-dimensional computational fluid dynamics. Vascular histology was unchanged proximal and distal to the stent. Time-dependent NH was localized within the stented region and was greatest in regions exposed to low WSS and acute elevations in spatial WSS gradients. The lowest values of WSS spatially localized to the stented area of a theoretical artery progressively increased after 14 and 21 days as NH occurred within these regions. This NH abolished spatial disparity in distributions of WSS. The results suggest that stents may introduce spatial alterations in WSS that modulate NH in vivo.

Collateral function is impaired in aged F344 × BN rats with aortic pathology

Introduction: This study was performed to determine if hindlimb collateral function is impaired in a rat model which develops age-related vascular pathology similar to that observed in humans. Methods: Rats aged 6 (n = 6) and 24 (n = 6) months were studied. Under pentobarbital anesthesia, iliac artery blood flow was measured before and during occlusion of the femoral artery. The thoracic aorta, abdominal aorta, iliac arteries, and femoral arteries were harvested after perfusion fixation with paraformaldehyde and subsequently plastic embedded, sectioned, and stained. Results: Prior to occlusion, iliac flows were 3.0 ± 0.01 mL/min and 3.5 ± 0.02 mL/min respectively in 6 and 24 month old rats. After occlusion in the young rats, flow dropped initially by 0.8 ± 0.01 mL/min and then recovered by 0.7 ± 0.02 mL/min, essentially reaching pre-occlusion values. In 24 month old animals, flow decreased initially by 0.9 ± 0.01 mL/min but only recovered 0.4 ± 0.01 mL/min (p < 0.05). Intimal thickening was apparent only in the thoracic aorta of 24 month old animals. Conclusions: The increase in iliac artery blood flow after femoral artery occlusion reflects dilation of collateral vessels. The reduced compensation in older animals suggests that flow-dependent collateral dilation is reduced. This is consistent with studies which have demonstrated a progressive increase in endothelial dysfunction with aging. These observations together with the aortic pathology are consistent with the hypothesis that vascular aging not only promotes large vessel pathology, but also suppresses the capacity for compensation such as collateral dilation.

Effect of Chronic Ischemia on Constitutive and Inducible Nitric Oxide Synthase Expression in Erectile Tissue

Arterial occlusive disease is one of the leading causes of organic erectile dysfunction (ED). Recent studies have shown that the incidence of cardiovascular disease closely correlates with the prevalence of ED. Also, ED is thought to be an early signal of impending cardiovascular problems. We previously found that the atherosclerosis of iliohypogastric arteries in the rabbit causes ED, down-regulates cavernosal neuronal nitric oxide synthase (nNOS) gene expression, and impairs NO synthesis. The goal of this study was to determine the effect of atherosclerosis-induced ischemia on cavernosal nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) expression and NO-mediated smooth muscle relaxation in the rabbit. Our study showed that iliac artery blood flow, intracavernosal blood flow, and intracavernosal oxygen tension were unchanged 4 weeks after the induction of arterial atherosclerosis, whereas they were significantly diminished at weeks 8 and 16. Erectile responses to nerve stimulation and cavernosal smooth muscle relaxation were unchanged at week 4 and were significantly diminished at weeks 8 and 16 after the induction of atherosclerosis. Western blotting showed that cavernosal nNOS and eNOS protein levels were unaffected at week 4 but were significantly decreased at weeks 8 and 16 after the induction of atherosclerosis. iNOS protein, however, markedly increased during the course of the induced arterial disease. Immunohistochemical staining showed no change in cavernosal eNOS or nNOS expression at week 4. A dramatic decrease in both was evident at 8 and 16 weeks. iNOS expression progressively increased between 4 and 16 weeks of atherosclerosis. Down-regulation of nNOS and eNOS, along with up-regulation of iNOS, may explain ischemic cavernosal smooth muscle relaxation impairment in the rabbit. Ischemically altered NOS expression may be of great pathophysiologic importance in atherosclerosis-induced ED. These data may provide further insight into the mechanism of arteriogenic ED.

Alteration of urothelial-mediated tone in the ischemic bladder: role of eicosanoids.

Previously we showed that ischemia alters bladder smooth muscle contractility in the rabbit. This study investigates the role of urothelium and eicosanoid-release in ischemic bladder smooth muscle instability. Male New Zealand white rabbits were divided into treated (n = 12) and age-matched control (n = 10) groups. The treated group underwent balloon endothelial injury of the iliac arteries, and then received 4 weeks of cholesterol diet, followed by 4 weeks of regular diet. The control group received a regular diet for 8 weeks. After 8 weeks, blood flow for both the iliac arteries and the bladder as well as bladder oxygen tension were recorded. In one-half of each ischemic and control bladder, the urothelium was removed. Bladder tissues were processed for organ bath and enzyme-immunoassay (EIA) of prostaglandins (PGs) and leukotrienes (LTs). A significant decrease in iliac arterial blood flow, bladder wall blood flow, and bladder oxygen tension was found in the treated group. Bladder ischemia increased the frequency and amplitude of baseline spontaneous smooth muscle contractility. Ischemic tissues with urothelium (Uro+) demonstrated significant increases in the contractile response to electrical field stimulation (EFS) and carbachol relative to control Uro+ tissues. Urothelial removal increased smooth muscle contraction in the control tissues but had no significant effect in the ischemic/hypoxic tissues. Contraction of control tissues without urothelium (Uro-) was similar to contraction of ischemic Uro+ tissues. Contractions of ischemic Uro+ and control Uro- tissues were unchanged after treatment with the cyclooxygenase (COX) inhibitor indomethacin, while they were significantly reduced by the 5-lipoxygenase (5-LO) inhibitor NDGA. EIA showed no change in PGs release from the ischemic urothelium, but significant increase in PGF(2-alpha) and thromboxane A(2) release from the ischemic suburothelial tissue. Ischemia increased the release of LTB(4), LTC(4), and LTE(4) from both urothelium and suburothelial tissue. Our studies suggest loss of urothelial-mediated tone and LTs-mediated smooth muscle instability in the chronically ischemic/hypoxic bladder.

Effects of tumor necrosis factor, endothelin and nitric oxide on hyperdynamic circulation of rats with acute and chronic portal hypertension.

To evaluate the effect of tumor necrosis factor (TNF), endothelin (ET) and nitric oxide (NO) on hyperdynamic circulation (HC) of rats with acute and chronic portal hypertension (PHT). Chronic portal hypertension was induced in Wistar rats by injection of carbon tetrachloride. After two weeks of cirrhosis formation, L-NMMA (25 mg/kg) was injected into one group of cirrhotic rats via femoral vein and the experiment was begun immediately. Another group of cirrhotic rats was injected with anti-rat TNFalpha (300 mg/kg) via abdominal cavity twice within 48 h and the experiment was performed 24 h after the second injection. The blood concentrations of TNFalpha, ET-1 and NO in portal vein and the nitric oxide synthase (NOS) activity in hepatic tissue were determined pre-and post-injection of anti-rat TNFalpha or L-NMMA. Stroke volume (SV), cardiac output (CO), portal pressure (PP), superior mesenteric artery blood flow (SMA flow) and iliac artery blood flow (IAflow) were measured simultaneously. Acute portal hypertension was established in Wistar rats by partial portal-vein ligation (PVL). The parameters mentioned above were determined at 0.5 h, 24 h, 48 h, 72 h and 120 h after PVL. After the formation of stable PHT, the PVL rats were injected with anti-rat TNFalpha or L-NMMA according to different groups, the parameters mentioned above were also determined. In cirrhotic rats, the blood levels of TNFalpha, NO in portal vein and the liver NOS activity were significantly increased (P<0.05) while the blood level of ET-1 was not statistically different (P>0.05) from the control animals (477.67+/-83.81 pg/mL vs 48.87+/-32.79 pg/mL, 278.41+/-20.11 micromol/L vs 113.28+/-14.51 micromol/L, 1.81+/-0.06 u/mg.prot vs 0.87+/-0.03 u/mg.prot and 14.33+/-4.42 pg/mL vs 8.72+/-0.79 pg/mL, respectively). After injection of anti-rat TNFalpha, the blood level of TNFalpha was lower than that in controls (15.17+/-18.79 pg/mL vs 48.87+/-32.79 pg/mL). The blood level of NO and the liver NOS activity were significantly decreased, but still higher than those of the controls. The blood level of ET-1 was not significantly changed. PP, SV, CO, SMAflow and IAflow were ameliorated. After injection of L-NMMA, the blood level of NO and the liver NOS activity were recovered to those of the controls. PP and CO were also recovered to those of the controls. SV, SMAflow and IAflow were ameliorated. In PVL rats, the blood levels of TNFalpha, NO in portal vein and the liver NOS activity were gradually increased and reached the highest levels at 48 h after PVL. The blood level of ET-1 among different staged animals was not significantly different from the control animals. PP among different staged animals (2.4+/-0.18 kPa at 0.5 h, 1.56+/-0.08 kPa at 24 h, 1.74+/-0.1 kPa at 48 h, 2.38+/-0.05 kPa at 72 h, 2.39+/-0.16 kPa at 120 h) was significantly higher than that in controls (0.9+/-0.16 kPa). After injection of anti-rat TNFalpha in 72 h PVL rats, the blood level of TNFalpha was lower than that in controls (14+/-14 pg/mL vs 48.87+/-32.79 pg/mL). The blood level of NO and the liver NOS activity were significantly decreased, but still higher than those of the controls. The blood level of ET-1 was not significantly changed. PP was decreased from 2.38+/-0.05 kPa to 1.68+/-0.12 kPa, but significantly higher than that in controls. SV, CO, SMAflow and IAflow were ameliorated. After injection of L-NMMA in 72 h PVL rats, the blood level of NO and the liver NOS activity were recovered to those of the controls. PP, SV, CO, SMAflow and IAflow were also recovered to those of the controls. NO plays a critical role in the development and maintenance of HC in acute PHT and is a key factor for maintenance of HC in chronic PHT. TNFalpha may not participate in the hemodynamic changes of HC directly, while play an indirect role by inducing the production of NO through activating NOS. No evidence that circulating ET-1 plays a role in both models of portal hypertension has been found.