Sulodexide Inhibits Arterial Contraction via the Endothelium-Dependent Nitric Oxide Pathway.

Background/Objectives: Sulodexide (SDX) is a drug known for restoring the glycocalyx, thereby offering endothelial protection and regulating permeability. Additionally, it has antithrombotic and anti-inflammatory properties and has shown arterial vasodilatory effects. Endothelial cells play a crucial role in maintaining homeostasis, with their dysfunction being a key contributor to loss in vasodilatory response, especially in arterial pathologies. The aim of this study was to investigate the effects of SDX on stimulated vascular tonus in human arterial samples and to assess the function of the endothelial layer as a source of nitric oxide (NO). Methods: A total of 16 internal mammary artery remnants from coronary artery bypass graft surgeries were dissected into endothelium-intact and endothelium-denuded groups (n = 8 each). The arterial rings were equilibrated under tension, with their basal tonus recorded before and after phenylephrine stimulation. SDX's impact on arterial contraction was assessed through cumulative dose-response curves. NO synthase inhibitor (Nω-nitro-L-arginine methyl ester) was used to assess SDX's vasodilatory effect over the NO pathway. Results: SDX application resulted in concentration-dependent vasorelaxation in both endothelium-intact and endothelium-denuded groups at certain doses. However, the inhibitory effect of SDX was more pronounced in endothelium-intact rings at higher doses compared to endothelium-denuded rings (p < 0.05). Similar inhibition of contraction curves was achieved for both endothelium-intact and endothelium-denuded rings after L-NAME pre-incubation, suggesting a necessity for NO-related endothelial pathways. Conclusions: SDX exerts a concentration-dependent inhibition on arterial contraction, emphasizing the critical role of an intact endothelium and NO-mediated pathways in this process. This underscores SDX's potential in treating endothelial dysfunction-related pathologies.

Sulodexide Develops Contraction in Human Saphenous Vein via Endothelium-Dependent Nitric Oxide Pathway.

Chronic venous disease (CVD) is a proqgressive and underestimated condition related to a vicious circle established by venous reflux and endothelial inflammation, leading to vein dilation and histology distortion, including loss of media tone. Sulodexide (SDX) is a drug restoring the glycocalyx that demonstrated endothelial protection and permeability regulation, together with anti-thrombotic and anti-inflammatory roles. In the lab it also exhibited vein contractility function. The aim of the present study was to show the possible role of endothelium and nitric oxide pathway on SDX's veno-contractile effect on human saphenous veins. The remnants of great saphenous vein (GSV) segments (n = 14) were harvested during coronary artery bypass graft surgery. They were dissected as endothelium-intact (n = 8) and denuded rings (n = 6). First, a viability test was carried out in bath with Krebs-Henseleit solution to investigate a control and basal tension value. After this, cumulative doses of SDX were applied to rings and contraction values were studied in endothelium-intact phenylephrine (PheE, 6 × 10-7 M) pre-contracted vein rings. Finally, endothelium-intact PheE pre-contacted vein rings were treated by nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10-4 M) for 10 min. Contraction protocol was applied, and contraction values were measured in cumulative doses of SDX. The same protocol was applied to endothelium-denuded vein rings to investigate the effect of SDX. Saphenous vein rings showed an increase in contraction to cumulative doses of SDX. In endothel-intact rings, KCL-induced contraction from 92.6% ± 0.3 to 112.9% ± 0.4 with cumulative SDX doses. However, SDX did not show any veno-contractile effect on endothel-denuded rings. In denuded rings contraction responses measured from 94.9% ± 0.3 to 85.2% ± 0.3 with increasing doses of SDX, indicating no significant change. Nitric oxide synthase inhibitor (L-NAME) prohibited the contraction response of the sulodexide in all dosages, indicating that the contractile function of SDX was mediated by endothelial derived nitric oxide. Results of endothel-intact and denuded rings with L-NAME showed a similar incline with denuded rings with SDX only. The results confirmed SDX's veno-contractile effect in human samples, by means of nitric oxide synthase pathways involvement.

Effect of perioperative intravenous magnesium sulfate on postoperative pain after iliac venous stenting.

BACKGROUND: The aim of the present study was to evaluate the effect of perioperative intravenous (IV) magnesium sulfate (MS) on low back pain (LBP) severity after iliac venous stent implantation. METHODS: The present study was a single-center retrospective study. A total of 97 patients who had undergone iliac venous stenting for post-thrombotic syndrome between January 1, 2019 and January 11, 2021 were considered for inclusion in the present study. The patients were divided into two groups: those who had received perioperative MS infusions (group M) and those who had not (control group; group C). Group M was given an IV bolus of 20 mg/kg before anesthesia induction and an IV MS infusion of 20 mg/kg/h during the procedure. Postoperative LBP severity was evaluated using the numerical rating scale at 1, 6, 12, and 24 hours after the procedure. The total tramadol consumption within 24 hours was measured with the help of a patient-controlled analgesia device. Moreover, additional analgesic needs and complaints of nausea and vomiting were evaluated. RESULTS: A total of 97 patients were considered for inclusion in the present study. Of the 97 patients, 29 were excluded because of a lack of follow-up data, leaving 68 patients for the final analysis (group M, n = 36; group C, n = 32). The demographic data, body mass index, sedation time, procedure time, and stented side data were similar between the two groups (P > .05). The rates of atropine and ephedrine use during the procedure were similar between the two groups (P > .05). The numerical rating scale scores were significantly lower for group M at all follow-up periods (P < .001). The total tramadol consumption at 24 hours postoperatively was 191.94 ± 68.194 mg for group M and 378.75 ± 31.367 mg for group C (P < .001). Additional analgesics were used by 8 patients (22.2%) in group M and 17 patients (53.1%) in group C. Additional analgesic needs were significantly lower for group M (P = .008). Nausea and vomiting were observed in six (19.4%) and four (11.1%) patients in group M and eight (32%) and five (15.6%) patients in group C, respectively (P > .05). CONCLUSIONS: For patients undergoing iliac venous stenting, perioperative MS infusion was an effective and safe treatment option that reduced LBP severity, opioid consumption, and the need for additional analgesics in the acute postoperative period.

Complications and pitfalls of central venous port catheters: experience with 782 patients with cancer.

BACKGROUND: The clinical use of port catheters has become widespread because they provide a safe and easy vascular route. Such widespread use of vascular port catheters has revealed early and late complications. AIM: This study was evaluated the early and late noninfectious complications and present precautions and pitfalls to handle these complications. METHODS: The retrospective observational study comprised 801 vascular port catheters inserted into 782 adult patients for various reasons between 2010 and 2018. Patient demographic, indications for port catheter implantation, port catheter types, and insertion sides were noted. Port catheter implantation related early and late complications were recorded. RESULTS: The subclavian vein was selected as a target vein in almost all of the interventions (98.9%). Similarly, right-sided veins were used in about 90% of patients. The most common problem was technical issues related to the interventions. If venous cannulation was challenging, ultrasonography and fluoroscopy guidance roadmap technique were used. Most serious complication was pneumothorax in 7 patients. In the late period, the most common problem was thrombotic occlusion of the catheter. In two-thirds of these patients, thrombolytic therapy for thrombosed port catheters may rescue some catheters and avoid secondary port catheter insertions. CONCLUSIONS: Despite these benefits, port catheters are associated with various complications. However, most of these complications can be effectively prevented by proper techniques and easily applied precautions.