Cremasteric Arteries Research Articles

Gubernaculum-sparing orchiopexy versus gubernaculum excision; A randomized trial on success and atrophy rates

Previous studies showed that extra blood supply can decrease testicular atrophy following laparoscopic orchiopexy. We evaluated the impact of preserving the gubernacular attachment (which contains blood supply from cremasteric artery and its anastomoses) on atrophy rates following open conventional orchiopexy. This double-blinded randomized trial was implemented from March 2022 to September 2023. Included boys with non-palpable testis, even with examination under anesthesia, underwent diagnostic laparoscopy to evaluate the testis's location and size. Nubbin testes and those with > 2-cm distance from the internal inguinal ring. Participants were assigned into two groups (gubernaculum sparing (GS) and excision (GE)) by permuted block randomization. Overall success was defined as achieving both morphologic success (atrophy <20% of the intraoperative size) and anatomical success (scrotal or high-scrotal locations). Boys were followed at three- and six-month post-surgery via ultrasound. Independent t-test, repeated ANOVA, and Friedman's tests were used where appropriate. Of 92 boys (105 UDTs overall), 75 testes (36 in GS, 39 in GE groups) were used in the analysis. The mean age of participants was 25±17 months (range 6-84). The mean testis size of cases intraoperatively was 460±226, 396±166, and 520±258mm3 among all participants, GS, and GE cases, respectively. Both groups showed a significant decrease in testicular volume on both follow-up checkpoints, but this decrement was significantly higher in the GE group (p<0.001). The anatomical success rate was significantly higher among GS boys (97.2% versus 82.1%; p=0.038). The overall success rate was significantly higher for the GS group (61.1% versus 25.6%; p=0.002). Although mean testicular volume decreased in both groups, we found superior morphologic and overall success rates among the GS group. The greatest size reduction was noted at the three-month post-surgery compared to the six-month checkpoint. https://irct.ir/trial/58842.

ANGIOEMBOLISATION OF CREMASTERIC ARTERY FOR SCROTAL HAEMATOMA FOLLOWING HERNIAL REPAIR

Cremasteric artery is a branch of inferior epigastric artery supplying the cremaster muscle and coverings of the cord. The possible consequence of injury to this artery is scrotal haematoma. We present a case of haemorrhage from unexpected cresmastric artery injury post-hernioplasty treated with angioembolisation. To the best of our knowledge, this has not been reported in literature.&#x0D; A 66-year-old gentleman with left indirect inguinal hernia underwent a left inguinal hernioplasty in our institution with no immediate complications. However he presented to the emergency department the day after the procedure with complaints of rapidly worsening painful left scrotal swelling accompanied with symptoms of intestinal obstruction. Emergency laparotomy and re-do left hernioplasty was performed, revealing a strangulated inguinoscrotal hernia. Post-operatively, there was non-resolving scrotal swelling with a drop in the haemoglobin level; from 11.9g/dl to 8.5g/dl requiring packed cell transfusion. CT angiogram revealed active contrast extravasation from the left cremasteric artery. Angiographic run confirmed the finding and the left cresmatric artery was superselectively cannulated with a 1.9Fr microcatheter and embolization done with 0.5mm microcoil. Ultrasound scan 24-hour post-procedure showed patent proximal vessel. Clinically there was a reduction of the left scrotal swelling and the haemoglobin remained stable. &#x0D; Cremasteric artery courses laterally deep into the fascia transversalis entering the cord deep to the internal spermatic fascia to supply the cremaster muscle and coverings of the cord. This course renders the artery to be prone for injury during procedure such as hernioplasty; one of the possible consequences is scrotal haematoma. This artery is usually small in caliber and its identification is important for efficient and effective treatment.&#x0D; Angioembolisation is able to treat this injury with superior precision owing to its ability for localization and selective cannulation of the offending vessel.

Histological differences between the central and peripheral areas of the testes of busulfan-administered mice.

Busulfan is an anticancer drug known to cause serious damage to seminiferous tubules in the testes and deplete germ cells in human and animal models. The testicular artery is anastomosed with deferential and cremasteric arteries and is divided into capsular arteries, which give rise to the centripetal arteries and then recurrent arteries. The arterial blood in the testicular tissue is supplied by such a consequent system of arterial vessels, in order from the peripheral to the central area. As anticancer drugs are generally distributed throughout the whole body via the bloodstream and the running and distribution of arteries differ among the testicular areas, we hypothesized that the efficacy of busulfan differs in different testicular areas, particularly between the central and peripheral areas. In this study, busulfan was intraperitoneally injected at 40 mg/kg body weight into C57BL/6J male mice. After 28 days, in busulfan-treated mice, the diameters of seminiferous tubules were significantly higher in the central than in the peripheral area of the testes. The seminiferous tubular areas also significantly decreased in the peripheral areas compared with the central areas. The number of germ cells per seminiferous tubule was significantly higher in the central than in the peripheral area. Sertoli cell nuclei were detached into the lumen in the peripheral area. The number of Leydig cells was significantly lower in the peripheral areas. These data suggest that the effects of busulfan differ between the central and peripheral areas of the testis at 4 weeks after busulfan administration.

Laparoscopic Varicocelectomy by Artery Preserving and Mass Ligation Technique- A Comparative Study

Background- There are multiple methods of varicocele treatment. No single approach is adopted as the best therapeutic option. Laparoscopic varicocelectomy (LV) is one of them. Artery sparing laparoscopic varicocelectomy was found to have high recurrence in literature. Retroperitoneal mass ligation of testicular vein and artery was first done in original Palomo operation. Chance of missing some veins are also less if mass ligation is done in LV. Testes get blood supply from testicular artery, cremasteric artery and artery to the vas. For this reason ligation of the testicular artery in the abdomen do not cause ischemia to testes. We present our experience on comparative study between LV with mass ligation (ML) and artery preserving (AP) technique. We compared the operation time, outcome, and complication in two groups of patients. Methods-Forty-eight varicoceles, both unilateral and bilateral, were operated over a period of three years. Twenty three underwent ligation of veins alone and twenty-five underwent ligation of testicular veins and artery en-mass. They were followed up for a period of three months after surgery. We collected all data in a prospective manner. Results: The average operation time for the artery-preserved and the mass ligated group was 41±5 minutes and 27±3 minutes respectively. Average post-operative hospital stay was 46±12 hrs. and 32±7 hours respectively. There were no technical failures in either group. Complications and recurrence were less in the mass-ligation than in the artery-preserved group. On an average follow-up of 3 months all patients remained asymptomatic and had complete reduction in the size of the varicoceles. There were no incidence of testicular atrophy in either group. Conclusion: Laparoscopic varicocelectomy with mass ligation technique is safe, effective, less time consuming and easy to perform. Recurrence and post-operative complications are minimum. This should preferably be done with mass ligation with an attempt to spare lymphatics.

Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries.

Reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide, are reported to contribute to the dynamic regulation of contractility in various arterial preparations, however, the situation in pressurized, myogenically active resistance arteries is much less clear. In the present study, we have utilized established pharmacological inhibitors of NADPH oxidase activity to examine the potential contribution of ROS to intrinsic myogenic contractility in adult Sprague–Dawley rat resistance arteries and responses to vasoactive agents acting via the endothelium (i.e., acetylcholine, SKA-31) or smooth muscle (i.e., sodium nitroprusside, phenylephrine). In cannulated and pressurized cremaster skeletal muscle and middle cerebral arteries, the NOX inhibitors 2-acetylphenothiazine (2-APT) and VAS2870, selective for NOX1 and NOX2, respectively, evoked concentration-dependent inhibition of basal myogenic tone in a reversible and irreversible manner, respectively, whereas the non-selective inhibitor apocynin augmented myogenic contractility. The vasodilatory actions of 2-APT and VAS2870 occurred primarily via the vascular endothelium and smooth muscle, respectively. Functional responses to established endothelium-dependent and –independent vasoactive agents were largely unaltered in the presence of either 2-APT or apocynin. In cremaster arteries from Type 2 Diabetic (T2D) Goto-Kakizaki rats with endothelial dysfunction, treatment with either 2-APT or apocynin did not modify stimulus-evoked vasoactive responses, but did affect basal myogenic tone. These same NOX inhibitors produced robust inhibition of total NADPH oxidase activity in aortic tissue homogenates from control and T2D rats, and NOX isozymes 1, 2 and 4, along with superoxide dismutase 1, were detected by qPCR in cremaster arteries and aorta from both species. Based on the diverse effects that we observed for established, chemically distinct NOX inhibitors, the functional contribution of vascular NADPH oxidase activity to stimulus-evoked vasoactive signaling in myogenically active, small resistance arteries remains unclear.

Testicular arteries anatomy applied to fowler-sthephens surgery in high undescended testis - a narrative review.

ABSTRACTObjectives:In this review we will describe the testicular vessels anatomy and the implications of these vessels in surgical treatment of high undescended testis.Material and Methods:We performed a narrative review of the literature about the role of the testicular arteries anatomy in the treatment of high undescended testis. We also studied two human testes to illustrate the testicular vascularization.Results:Each testis is irrigated by three arteries: testicular artery (internal spermatic artery), a branch of the right aorta; deferential artery (vasal artery), a branch of the inferior vesicle artery that originates from the anterior trunk of internal iliac artery and cremasteric artery (external spermatic artery), a branch of the inferior epigastric artery. There are important communications among the three arteries with visible anastomotic channels between the testicular and deferential arteries.Conclusions:Laparoscopic transection of the testicular vessels by dividing the spermatic vessels (Fowler-Stephens surgery) is safe in patients with high abdominal testis due to the great collateral vascular supply between testicular, vasal and cremasteric arteries; also, two-stage Fowler-Stephens orchiopexy appears to carry a higher rate of success than the single stage approach.

Activation of Nav channels by veratridine in mesenteric arteries: Contractile or relaxation responses?

Veratridine (VTD), a selective activator of voltage-gated Na + (Nav) channels, triggers contractile responses in mesenteric arteries (MA), by increasing intracellular Ca2+ mediated by Na + /Ca 2+ exchanger (NCX) in smooth muscle cells (SMC). However, VTD induces endothelium-dependent relaxation of retinal and cremaster arteries. These opposite VTD-responses gives rise to the question as to whether Nav channels play a role in vascular tone. We aim to characterize the contribution of Nav channels to vascular tone in MA. Since Nav channels are expressed in SMC, endothelial cells (EC) and nerve terminal endings of arteries, our aim is also to identify those which are responsible of VTD-evoked vasomotor responses. The VTD-induced contractile responses of first order mesenteric arteries (FOMA) and cecolic arteries (CA) of mice were recorded by wire myography. EC were used to characterize Ca 2+ responses using FURA-2 probe. Western blot and absolute RT-qPCR were used to characterize Nav channels and NCX expression. Nav1.2 channels are expressed in both SMC and EC of MA. VTD elicits contraction of FOMA, which is abolished by prazosin. Surprisingly, VTD induces relaxation of CA. This vasorelaxation is resistant to prazosin and supressed by atropine. VTD-induced relaxation is inhibited by eNO-synthase inhibitor (L-NNA) and NCX antagonists. Morever, NCX1 is the main NCX isoform expressed in EC. Finally, acetylcholine-induced Ca 2+ reponses are inhibited by NCX antagonists in endothelial cells. VTD induces opposite contractile responses in isolated mesenteric arteries. In fact, VTD activates Nav channels of sympathetic neurons in FOMA, and parasympathetic neurons in CA, leading to noradrenaline and acetylcholine release, respectively. Thus, the vascular tone of both arteries are differently regulated by the autonomic nervous system. Finally, acetylcholine triggers Ca 2+ -activation of eNO-synthase mediated by NCX1 in CA.

KCa channel activation normalizes endothelial function in Type 2 Diabetic resistance arteries by improving intracellular Ca2+ mobilization

BackgroundEndothelial dysfunction is an early pathogenic event in the progression of cardiovascular disease in patients with Type 2 Diabetes (T2D). Endothelial KCa2.3 and KCa3.1 K+ channels are important regulators of arterial diameter, and we thus hypothesized that SKA-31, a small molecule activator of KCa2.3 and KCa3.1, would positively influence agonist-evoked dilation in myogenically active resistance arteries in T2D. MethodologyArterial pressure myography was utilized to investigate endothelium-dependent vasodilation in isolated cremaster skeletal muscle resistance arteries from 22 to 24 week old T2D Goto-Kakizaki rats, age-matched Wistar controls, and small human intra-thoracic resistance arteries from T2D subjects. Agonist stimulated changes in cytosolic free Ca2+ in acutely isolated, single endothelial cells from Wistar and T2D Goto-Kakizaki cremaster and cerebral arteries were examined using Fura-2 fluorescence imaging. Main findingsEndothelium-dependent vasodilation in response to acetylcholine (ACh) or bradykinin (BK) was significantly impaired in isolated cremaster arteries from T2D Goto-Kakizaki rats compared with Wistar controls, and similar results were observed in human intra-thoracic arteries. In contrast, inhibition of myogenic tone by sodium nitroprusside, a direct smooth muscle relaxant, was unaltered in both rat and human T2D arteries. Treatment with a threshold concentration of SKA-31 (0.3 μM) significantly enhanced vasodilatory responses to ACh and BK in arteries from T2D Goto-Kakizaki rats and human subjects, whereas only modest effects were observed in non-diabetic arteries of both species. Mechanistically, SKA-31 enhancement of evoked dilation was independent of vascular NO synthase and COX activities. Remarkably, SKA-31 treatment improved agonist-stimulated Ca2+ elevation in acutely isolated endothelial cells from T2D Goto-Kakizaki cremaster and cerebral arteries, but not from Wistar control vessels. In contrast, SKA-31 treatment did not affect intracellular Ca2+ release by the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor cyclopiazonic acid. ConclusionsCollectively, our data demonstrate that KCa channel modulation can acutely restore endothelium-dependent vasodilatory responses in T2D resistance arteries from rats and humans, which appears to involve improved endothelial Ca2+ mobilization.

Experimental Subarachnoid Hemorrhage Drives Catecholamine-Dependent Cardiac and Peripheral Microvascular Dysfunction.

Subarachnoid hemorrhage (SAH) is a devastating cerebral event caused by an aneurysmal rupture. In addition to neurological injury, SAH has significant effects on cardiac function and the peripheral microcirculation. Since these peripheral complications may exacerbate brain injury, the prevention and management of these peripheral effects are important for improving the overall clinical outcome after SAH. In this investigation, we examined the effects of SAH on cardiac function and vascular reactivity in a well-characterized blood injection model of SAH. Standard echocardiographic and blood pressure measurement procedures were utilized to assess cardiac function and hemodynamic parameters in vivo; we utilized a pressure myography approach to assess vascular reactivity in cremaster skeletal muscle resistance arteries ex vivo. We observed that elevated catecholamine levels in SAH stun the myocardium, reduce cardiac output and augment myogenic vasoconstriction in isolated cremaster arteries. These cardiac and vascular effects are driven by beta- and alpha-adrenergic receptor signaling, respectively. Clinically utilized adrenergic receptor antagonists can prevent cardiac injury and normalize vascular function. We found that tumor necrosis factor (TNF) gene deletion prevents the augmentation of myogenic reactivity in SAH: since membrane-bound TNF serves as a mechanosensor in the arteries assessed, alpha-adrenergic signaling putatively augments myogenic vasoconstriction by enhancing mechanosensor activity.

Alpha-Dystroglycan Supports Platelet Aggregation and Thrombus Formation

No relevant conflicts of interest to declare.

Nerve‐Mediated Responses in Isolated Myogenic and Non‐Myogenic Arteries

Small arteries and arterioles of the resistance vasculature can exhibit a basal level of vasoconstriction, or myogenic tone, in response to an increase in intraluminal pressure. Myogenic tone occurs without influence from perivascular nerves and the endothelium, and is most likely dependent on stretch‐activated receptors which mediate smooth muscle depolarization and contraction. The aim of the current investigation was to compare nerve‐mediated responses in myogenic and non‐myogenic arteries, as data on modulation of myogenic tone by neurotropic factors is lacking.To address this aim, rat mesenteric and cremasteric arteries were excised and studied as non‐myogenic and myogenic arteries, respectively. A combination of immunohistochemistry, wire and pressure myography was employed to evaluate the effect of perivascular nerve activation by electrical field stimulation (EFS).Both artery types are innervated by sympathetic nerve fibres, as confirmed with staining for tyrosine hydroxylase observed only in the adventitial layer. Furthermore, both mesenteric and cremasteric arteries exhibited vasomotor responses to exogenously added norepinephrine (NE, 1 nM – 10 μM), phenylephrine (10 nM – 10 μM), and adenosine triphosphate (ATP, 10 nM – 10 μM). The sensitivity of the tissue to these agents was greater in the pressure myograph compared with the wire myograph, indicating the importance of considering data using EFS in pressurized arteries as well as from arteries under isometric tension.EFS (10 V, 50 pulses, 7 Hz, 1 ms pulse width) caused vasoconstriction of mesenteric arteries at 70 mmHg (27.5 ± 1.3%) which was attenuated by the voltage‐gated Na+ channel blocker tetrodotoxin (TTX, 1 μM, 6.6 ± 0.8%). Furthermore, EFS‐induced vasoconstriction was reduced by the α1‐adrenoceptor antagonist prazosin (1 μM, 18.7 ± 1.5%), the P2X1receptor antagonist NF 449 (10 μM, 17.5 ± 3.5%), and a combination of the two (10.9 ± 1%). The L‐type Ca2+ channel blocker nifedipine also attenuated the response (1 μM, 11.0 ± 2.8%), and in combination with TTX almost completely abolished it (1.4 ± 1.0%). Propranolol had no effect on the vasoconstriction (1 μM, 25.3 ± 2.9%) despite the presence of β‐adrenoceptors mediating vasodilation to exogenous NE. Most interestingly, EFS failed to elicit any response in cremasteric arteries at 80 mmHg with 47.4 ± 1.1% tone.This investigation highlights the importance of conducting experiments with EFS on pressurized arteries. EFS of mesenteric arteries confirmed a synergistic role for NE and ATP released from perivascular nerves and suggests an additional direct effect on L‐type voltage‐gated Ca2+ channels. Our data raise the question, why are arteries with a basal level of spontaneous tone insensitive to EFS, while non‐myogenic arteries are activated? Explaining these observations may be important for our understanding of neural control of blood flow in vivo.Support or Funding InformationThis research was supported by a British Heart Foundation PhD Studentship awarded to Hamish A L Lemmey.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Interspecific scaling of blood flow rates and arterial sizes in mammals.

This meta-study investigated the relationships between blood flow rate (Q̇; cm3s-1), wall shear stress (τw; dyncm-2) and lumen radius (ri; cm) in 20 named systemic arteries of nine species of mammals, ranging in mass from 23 g mice to 652 kg cows, at rest. In the dataset, derived from 50 studies, lumen radius varied between 3.7 µm in a cremaster artery of a rat and 11.2 mm in the aorta of a human. The 92 logged data points of [Formula: see text] and ri are described by a single second-order polynomial curve with the equation: [Formula: see text] The slope of the curve increased from approximately 2 in the largest arteries to approximately 3 in the smallest ones. Thus, da Vinci's rule ([Formula: see text]) applies to the main arteries and Murray's law ([Formula: see text]) applies to the microcirculation. A subset of the data, comprising only cephalic arteries in which [Formula: see text] is fairly constant, yielded the allometric power equation: [Formula: see text] These empirical equations allow calculation of resting perfusion rates from arterial lumen size alone, without reliance on theoretical models or assumptions on the scaling of wall shear stress in relation to body mass. As expected, [Formula: see text] of individual named arteries is strongly affected by body mass; however, [Formula: see text] of the common carotid artery from six species (mouse to horse) is also sensitive to differences in whole-body basal metabolic rate, independent of the effect of body mass.

Alpha1 -adrenergic stimulation selectively enhances endothelium-mediated vasodilation in rat cremaster arteries.

We have systematically investigated how vascular smooth muscle α 1‐adrenoceptor activation impacts endothelium‐mediated vasodilation in isolated, myogenically active, rat cremaster muscle 1A arteries. Cannulated cremaster arteries were pressurized intraluminally to 70 mmHg to induce myogenic tone, and exposed to vasoactive agents via bath superfusion at 34°C. Smooth muscle membrane potential was measured via sharp microelectrode recordings in pressurized, myogenic arteries. The α 1‐adrenergic agonist phenylephrine (25–100 nmol/L) produced further constriction of myogenic arteries, but did not alter the vasorelaxant responses to acetylcholine (0.3 μmol/L), SKA‐31 (an activator of endothelial Ca2+‐dependent K+ channels) (3 μmol/L) or sodium nitroprusside (10 μmol/L). Exposure to 0.25–1 μmol/L phenylephrine or 1 μmol/L norepinephrine generated more robust constrictions, and also enhanced the vasodilations evoked by acetylcholine and SKA‐31, but not by sodium nitroprusside. In contrast, the thromboxane receptor agonist U46619 (250 nmol/L) dampened responses to all three vasodilators. Phenylephrine exposure depolarized myogenic arteries, and mimicking this effect with 4‐aminopyridine (1 mmol/L) was sufficient to augment the SKA‐31‐evoked vasodilation. Inhibition of L‐type Ca2+ channels by 1 μmol/L nifedipine decreased myogenic tone, phenylephrine‐induced constriction and prevented α 1‐adrenergic enhancement of endothelium‐evoked vasodilation; these latter deficits were overcome by exposure to 3 and 10 μmol/L phenylephrine. Mechanistically, augmentation of ACh‐evoked dilation by phenylephrine was dampened by eNOS inhibition and abolished by blockade of endothelial KCa channels. Collectively, these data suggest that increasing α 1‐adrenoceptor activation beyond a threshold level augments endothelium‐evoked vasodilation, likely by triggering transcellular signaling between smooth muscle and the endothelium. Physiologically, this negative feedback process may serve as a “brake” to limit the extent of vasoconstriction in the skeletal microcirculation evoked by the elevated sympathetic tone.

Induction of inward arterial remodeling is ameliorated in vivo by inhibition of actin polymerization dynamics in a mouse model of hypertension

Hypertension is associated with structural changes to the resistance vasculature leading to a reduction in resistance artery diameter. This process is termed inward remodeling and is defined as a reduction in lumenal diameter under passive conditions. We posit that inward remodeling involves dynamic changes to the actin cytoskeleton that facilitate the movement and rearrangement of vascular smooth muscle cells around a smaller vascular lumen. Ex vivo, prolonged exposure to vasoconstrictors has been demonstrated to induce remodeling via g‐protein coupled receptors (GPCR) that activate the Rho signaling pathway and subsequently promote actin polymerization. We report here that vascular smooth muscle cells, propagated on nanopatterned culture‐ware to maintain their contractile phenotype, increase their ratio of filamentous (F) to globular (G)‐actin in response to GPCR activation by Norepinephrine and Angiotensin (Ang) II. One of the enzymes in the Rho signaling pathway implicated in the increase in F/G‐actin following GPCR activation is Lim Kinase, which phosphorylates and inactivates the actin severing enzyme, cofilin. In isolated rat cremasteric arteries we demonstrate that inhibition of Lim Kinase blocks inward remodeling in the presence of GPCR agonists and this is coincident with a reduction in cofilin phosphorylation. To examine the process in vivo, we utilized a transgenic mouse line that expresses smooth muscle actin (SMA)‐GFP in vascular smooth muscle cells to measure proximal arterial diameter noninvasively within the outer ears using confocal microscopy. Exposure of these mice to 1000 ng/kg/min of Ang II for two weeks resulted in a significant increase in mean arterial blood pressure. Both ears were imaged prior to Ang II infusion (Day 0) and after 14 days of infusion to assess inward remodeling. Starting at day 0, the right ear was injected with a bolus of a Lim Kinase inhibitor (10 uM) and the left ear was injected with vehicle. Injections were repeated every 4 days for a total of four injections. The vehicle exposed ears significantly inwardly remodeled in contrast to those exposed to the Lim Kinase inhibitor (Vehicle diameter = −15.95 % +/− 1.79 versus Lim Kinase inhibitor diameter = −1.75% +/− 1.78, P&lt;0.05). These data demonstrate that in vivo, Lim Kinase plays a necessary role in inward remodeling, and thus merits additional study as a potential therapeutic target in cardiovascular pathologies associated with inward remodeling.Support or Funding InformationNIH‐HL‐088105 to LAMThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Problem of Treatment of Abdominal Cryptorchidism by Orchidopexy of Fowler-Stephens from a Literature Review

The purpose of this work is to show the importance of the testicular artery and the deleterious effects of its injury from a literature review. There were 75 papers relating the testicular vascularization during the period from 1949 to 2017, coming from base electronic data. The corresponding articles concerned retrospective and prospective studies, review articles published in journals with editorial board, reading and science committee. These articles were written in French and English. The results show the success rate of the Fowler-Stephens orchidopexy was varied. The testicular artery maintains testicular thermoregulation, has an endocrine and nutrition roles, besides it was the artery of fertility. The intratesticular anastomoses weren’t seen between the testicular, cremasteric and differential arteries to rats, human and other mammalians. The testicular artery is the only artery that irrigates the testicular parenchyma. However, studies have observed extratesticular communications between the testicular, deferential and cremasteric arteries. In conclusion, the testicular artery is the main artery providing blood supply to the testicle. This artery plays an important role from a physiological point of view. Its lesions have important consequences on the functional and structural future of the testicle. This invites the strict respect of this artery during surgery spermatic cord or its environment.

Abstract 13974: Loss of Endothelial Primary Cilia Promotes Thrombus Formation in Mice

Introduction: Recent evidence suggest that endothelial cilia may suppress anti-inflammatory signaling and protect against atherosclerosis. Given that atherosclerosis predisposes to thrombosis, we hypothesized that endothelial cilia may also play a fundamental role in thrombogenesis. Hypothesis: We hypothesize that endothelial cilia is important for protection against thrombosis, and that loss of endothelial cilia promotes thrombus formation in mice. Methods: We focused on the intraflagellar transport 88 (IFT88) gene since endothelial deletion of IFT88 has been associated with decreased atherosclerotic lesions in a murine model of atherosclerosis. Key thrombosis-associated molecules were evaluated in IFT88-silenced human umbilical vein endothelial cells (HUVECs). Thrombi formation were monitored in the laser-injured cremasteric arteries of 8 week old male endothelial cell (EC) specific IFT88 knockout (EC-IFT88 -/- ) mice. Results: Compared to scrambled siRNA-treated HUVECs, those exposed to siIFT88 exhibited lower mRNA and protein levels of tissue factor pathway inhibitor (TFPI) and thrombomodulin, two key regulators of blood coagulation (-27% and -20%, respectively; N=3; p &lt; 0.05). We next examined the effect of IFT88 loss on thrombosis in mice. Upon laser-induced injury, we determined, via mean fluorescence intensity, that although the thrombi formed in the cremasteric arteries of EC-IFT88 -/- mice were similar in size to those produced in the wild type (WT) mice (2.2 ± 0.6 and 2.0 ± 0.3 AU, respectively; x10 6 ; N=32 thrombi; p=0.8), the average rate at which thrombi developed was significantly faster in the EC-IFT88 -/- mice relative to that in WT mice (97 ± 11 and 57 ± 3 AU/s, respectively; N=32 thrombi; p&lt;0.001). Conclusions: Loss of endothelial IFT88 results in decreased TFPI mRNA and protein expression in HUVECs. EC-IFT88 -/- mice exhibited earlier thrombi formation in our laser injury model of thrombosis. These results collectively suggest that endothelial cilia intricately regulates thrombus formation in a TFPI-dependent manner and represents a previously unrecognized target to modulate thrombosis susceptibility.

Adiponectin Receptor Agonist, AdipoRon, Causes Vasorelaxation Predominantly Via a Direct Smooth Muscle Action.

AdipoRon, an adiponectin receptor agonist, was recently proposed for treating insulin resistance and hyperglycemia. As adiponectin is vasoprotective via NO-mediated signaling, it was hypothesized that adipoRon similarly exerts potentially beneficial vasodilator effects. We therefore examined if adipoRon induces vasorelaxation and via what contributing mechanisms. Vascular function was assessed in skeletal muscle arteries from rats and cerebral/coronary arteries from mice using pressure and wire myography. Using qPCR, mRNA for adiponectin receptors was demonstrated in skeletal muscle, cerebral and coronary arteries. AdipoRon-caused vasorelaxation was not abolished by compound C (10 μM; AMPK inhibitor). Inhibition of endothelium-dependent relaxation with combinations of l-NAME/indomethacin/apamin/TRAM-34 only slightly reduced adipoRon-mediated vasorelaxation in cerebral and coronary arteries. EC-denuded cremaster arteries showed similar relaxant responses to adipoRon as in intact vessels, suggesting adipoRon directly impacts VSMCs. K(+) currents measured in VSMCs isolated from mouse basilar and LAD arteries were not altered by adiopRon. In cremaster arteries, adipoRon induced vasorelaxation without a marked decrease in VSMC [Ca(2+)]i . Adiponectin, itself, caused vasodilation in intact cremaster arteries while failing to cause significant dilation in EC-denuded arteries, consistent with endothelium dependency of adiponectin. AdipoRon exerts vasodilation by mechanisms distinct to adiponectin. The dominant mechanism for adipoRon-induced vasorelaxation occurs independently of endothelium-dependent relaxing factors, AMPK activation, K(+) efflux-mediated hyperpolarization and reductions in cytosolic [Ca(2+)]i .

Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis.

Short-term studies in subjects with diabetes receiving glucagon-like peptide 1 (GLP-1)-targeted therapies have suggested a reduced number of cardiovascular events. The mechanisms underlying this unexpectedly rapid effect are not known. We cloned full-length GLP-1 receptor (GLP-1R) mRNA from a human megakaryocyte cell line (MEG-01), and found expression levels of GLP-1Rs in MEG-01 cells to be higher than those in the human lung but lower than in the human pancreas. Incubation with GLP-1 and the GLP-1R agonist exenatide elicited a cAMP response in MEG-01 cells, and exenatide significantly inhibited thrombin-, ADP-, and collagen-induced platelet aggregation. Incubation with exenatide also inhibited thrombus formation under flow conditions in ex vivo perfusion chambers using human and mouse whole blood. In a mouse cremaster artery laser injury model, a single intravenous injection of exenatide inhibited thrombus formation in normoglycemic and hyperglycemic mice in vivo. Thrombus formation was greater in mice transplanted with bone marrow lacking a functional GLP-1R (Glp1r(-/-)), compared with those receiving wild-type bone marrow. Although antithrombotic effects of exenatide were partly lost in mice transplanted with bone marrow from Glp1r(-/-) mice, they were undetectable in mice with a genetic deficiency of endothelial nitric oxide synthase. The inhibition of platelet function and the prevention of thrombus formation by GLP-1R agonists represent potential mechanisms for reduced atherothrombotic events.

Abstract 10824: A Novel Role of Endothelial Autophagy in the Regulation of Thrombosis in vivo

Background: Arterial thrombosis of native and graft vessels is the inciting event for acute coronary syndromes, and the cause of significant cardiovascular morbidity and mortality. Endothelial cell (EC) dysfunction is believed to play a central role in the pathobiology of thrombosis. ECs are activated upon atherosclerotic plaque rupture and induce the expression of tissue factor (TF) with resultant atherothrombotic sequelae. The molecular basis of how endothelial TF is unregulated remains unknown. We hypothesize that endothelial autophagy, a process involved in cellular homeostasis and stress responses, plays a causal role in the expression of TF, and via this mechanism modulates thrombosis. Methods: We generated EC-specific ATG7 knockout (EC-ATG7 -/- ) mice using CreLoxP technology. We used small interfering RNA (siRNA) to knockdown and characterize the effect of ATG7 inhibition in HUVECs. We also employed intravital microscopy in FeCl 3 -induced carotid and laser-induced cremaster artery injury to evaluate thrombosis. Results: siRNA-mediated knockdown of ATG7 in HUVEC resulted in decreased TF mRNA and protein expression by over 60% (N=3-5; p&lt;0.05). Mean TF mRNA level in EC-ATG7 -/- mice was 43% lower (p&lt;0.05) compared with WT mice, after FeCl 3 -induced carotid artery injury. Time to carotid artery occlusion was significantly prolonged in EC-ATG7 -/- mice compared with WT mice (15.5±2.0 and 31.0±4.0 min, respectively; N=10/group; p=0.003). The time to maximum platelet fluorescence intensity in EC-ATG7 -/- mice was significantly prolonged relative to that for WT mice (1.0±0.6 and 2.3±1.2 min, respectively; N=33-38 thrombi; p&lt;0.0001). Thrombi size, as determined by platelet fluorescence intensity, were significantly smaller in EC-ATG7 -/- vs. WT mice, (1.8±0.7 and 8.2±2.9, respectively; x10 9 ; p=0.049). Conclusions: Knockdown of ATG7 resulted in reduced TF expression in vitro and in vivo. Compared to WT mice, EC-ATG7 -/- mice exhibited 2-fold greater occlusion times and reduced thrombi formation across all models of thrombosis. Taken together, these findings are evidence that endothelial autophagy regulates thrombosis in a TF-dependent manner, and underscores a novel and previously unrecognized target for antithrombotic drug development.

ENDOTHELIAL AUTOPHAGY REGULATES ARTERIAL THROMBUS FORMATION IN MICE

Arterial thrombosis occurs after rupture of an atherosclerotic plaque, wherein endothelial cells (ECs) become activated and express procoagulant molecules. The role of ECs in thrombosis has not been fully elucidated. Recent evidence suggests that loss of autophagy, an intracellular catabolic process, decreases von Willebrand factor secretion in cultured ECs and in mice. Inasmuch as ATG7 is a key catalyst of autophagy, we explored the potential role of autophagy in thrombogenesis using EC-specific ATG7 knockout (EC-ATG7-/-) mice and their wild-type (WT) littermate controls. Thrombosis was evaluated using intravital microscopy in FeCl3-induced carotid and mesenteric, and laser-induced cremaster artery injury models. Circulating platelet counts were enumerated and platelet surface expression of P-selectin and β3-integrin (β3) determined by fluorescence-activated cell sorting. Time to carotid artery occlusion was significantly prolonged in EC-ATG7-/- mice compared with WT mice (15.5±2.0 and 31.0±4.0 min, respectively; N=10/group; p=0.003). Time to mesenteric artery occlusion was also significantly longer in EC-ATG7-/- mice compared with WT mice (20.0±1.4 and 26.6±1.8 min, respectively; N=10/group; p=0.008). Thrombi in laser injured cremaster arterioles were examined in 38 WT and 33 EC-ATG7-/- mice. The time to maximum platelet fluorescence intensity in EC-ATG7-/- mice was significantly prolonged relative to that for WT mice (1.0±0.6 and 2.3±1.2 min, respectively; p<0.0001). Thrombi size, as determined by platelet fluorescence intensity, were significantly smaller in EC-ATG7-/- vs. WT mice, (1.8±0.7 and 8.2±2.9, respectively; x109; p=0.049). Despite these differences, platelet counts for WT and EC-ATG7-/- mice were not appreciably different (768±86 and 715±125, respectively; x106; N=10; p=0.3). In WT and EC-ATG7-/- mice, surface expression of β3 (68.4±24.4 and 42.8±21.1 AU, respectively; p=0.7) and P-selectin (6.0±1.2 and 5.2±0.8 AU, respectively; p=0.9) were also similar. Although EC-ATG7-/- mice exhibited extended occlusion times and reduced thrombi formation across all three models of thrombosis, platelet count, P-selectin levels and β3 expression were similar to those in WT mice. Taken together, these findings are evidence that endothelial autophagy contributes to thrombosis in a platelet-independent manner.