Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery.

BACKGROUND: Changes in K+ channel expression/function are associated with disruption of vascular reactivity in several pathological conditions, including hypertension, diabetes, and atherosclerosis. Gasotransmitters achieve part of their effects in the organism by regulating ion channels, especially K+ channels. Their involvement in hydrogen sulfide (H2S)-mediated vasorelaxation is still unclear, and data about human vessels are limited. OBJECTIVE: To determine the role of K+ channel subtypes in the vasorelaxant mechanism of H2S donor, sodium-hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA). RESULTS: NaHS (1 × 10-6-3 × 10-3 mol/L) induced a concentration-dependent relaxation of HIMA pre-contracted by phenylephrine and high K+. Among K+ channel blockers, iberiotoxin, glibenclamide, 4-aminopyridine (4-AP), and margatoxin significantly inhibited NaHS-induced relaxation of phenylephrine-contracted HIMA (P < 0.01), whereas in the presence of apamin/1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) combination, the HIMA relaxation was partially reduced (P < 0.05). The effect of NaHS was antagonized by NO pathway inhibitors, L-NAME and KT5823, and by cyclo-oxygenase inhibitor, indomethacin (P < 0.01). Under conditions of blocked NO/prostacyclin synthesis and release, apamin/TRAM-34 and glibenclamide caused further decrease in NaHS-induced vasorelaxation (P < 0.01), while iberiotoxin, 4-AP, and margatoxin were without additional effect (P > 0.05). In the presence of nifedipine, NaHS induced partial relaxation of HIMA (P < 0.01). CONCLUSION: Our results demonstrated that H2S donor, NaHS, induced concentration-dependent relaxation of isolated HIMA. Vasorelaxant mechanisms of H2S included direct or indirect opening of different K+ channel subtypes, KATP, BKCa, SKCa/IKCa, and KV (subtype KV1.3), in addition to NO pathway activation and interference with extracellular Ca2+ influx.

Impact of diabetes mellitus on the frequency of post-operative complications after carotid endarterectomy.

BACKGROUND: There is significant controversy surrounding the link between diabetes mellitus and post-operative complications after carotid endarterectomy (CEA). The aim of this study was to identify the possible effects of diabetes on the frequency of post-operative complications after CEA. METHODS: This prospective study was conducted at the Dedinje Clinic for Vascular Surgery, Belgrade. The patients who underwent CEA were divided into two groups: group A (37.7%) included 98 (35.1%) insulin-dependent and 181 (64.9%) insulin-independent diabetic patients, and group B (62.3%) comprised non-diabetic subjects. RESULTS: The pre-operative characteristics were similar, except for a greater prevalence of dyslipidaemia in patients with diabetes. Post-operative cardiac events occurred more often in patients with diabetes (3.6%) than in non-diabetic patients (1.1%) (p = 0.039); post-operative neurological events among patients with diabetes were 3.6% and among non-diabetics, 0.9% (p = 0.009). Peri-operative mortality rate was 2.5% in the diabetic group and 0.9% in the non-diabetic group. The total percentage of post-operative complications was two or more times higher in the diabetic group than the non-diabetic group (8.5 vs 18.3%, p < 0.001). CONCLUSIONS: Diabetes mellitus increased the surgical risk of CEA. Higher rates of mortality and post-operative complications were observed in patients being treated with oral antidiabetics than in those on insulin.

Carotid Restenosis Rate After Stenting for Primary Lesions Versus Restenosis After Endarterectomy With Creation of Risk Index.

PURPOSE: Carotid artery stenting (CAS) is an option for carotid restenosis (CR) treatment with favorable outcomes. However, CAS has also emerged as an alternative to carotid endarterectomy (CEA) for the management of patients with primary carotid stenosis. This study aimed to report CR rates after CAS was performed in patients with primary lesions versus restenosis after CEA, to identify predictors of CR, and to report both neurological and overall outcomes. MATERIALS AND METHODS: From January 2000 to September 2018, a total of 782 patients were divided into 2 groups: The CAS (prim) group consisted of 440 patients in whom CAS was performed for primary lesions, and the CAS (res) group consisted of 342 patients with CAS due to restenosis after CEA. Indications for CAS were symptomatic stenosis/restenosis >70% and asymptomatic stenosis/restenosis >85%. A color duplex scan (CDS) of carotid arteries was performed 6 months after CAS, after 1 year, and annually afterward. Follow-up ranged from 12 to 88 months, with a mean follow-up of 34.6±18.0 months. RESULTS: There were no differences in terms of CR rate between the patients in the CAS (prim) and CAS (res) groups (8.7% vs 7.2%, χ2=0.691, p=0.406). The overall CR rate was 7.9%, whereas significant CR (>70%) rate needing re-intervention was 5.6%, but there was no difference between patients in the CAS (prim) and CAS (res) groups (6.4% vs 4.7%, p=0.351). Six independent predictors for CR were smoking, associated previous myocardial infarction and angina pectoris, plaque morphology, spasm after CAS, the use of FilterWire or Spider Fx cerebral protection devices, and time after stenting. A carotid restenosis risk index (CRRI) was created based on these predictors and ranged from -7 (minimal risk) to +10 (maximum risk); patients with a score >-4 were at increased risk for CR. There were no differences in terms of neurological and overall morbidity and mortality between the 2 groups. CONCLUSIONS: There was no difference in CR rate after CAS between the patients with primary stenosis and restenosis after CEA. A CRRI score >-4 is a criterion for identifying high-risk patients for post-CAS CR that should be tested in future randomized trials.

Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein.

Hydrogen sulfide (H2 S) represents the third and the youngest member of the gaseous transmitters family. The dominant effect of H2 S on isolated vessels is vasodilation. As the mechanism of H2 S-induced relaxation in human vessels remains unclear, the present study aimed to investigate the effects of H2 S donor, sodium hydrosulfide (NaHS), on isolated human saphenous vein (HSV) and to determine the mechanism of action. Our results showed that NaHS (1 µM-3 mM) induced a concentration-dependent relaxation of endothelium-intact HSV rings pre-contracted by phenylephrine. Pre-treatment with L-NAME, ODQ and KT5823 significantly inhibited NaHS-induced relaxation, while indomethacin induced partial inhibition. Among K+ channel blockers, the combination of apamin and TRAM-34 significantly affected the relaxation produced by NaHS, while iberiotoxin and glibenclamide only reduced maximal relaxation of HSV. NaHS partially relaxed endothelium-intact rings pre-contracted by high K+ , as well as phenylephrine-contracted rings in the presence of nifedipine. Additionally, the incubation of HSV rings with NaHS increased NO production. These results demonstrate that NaHS produces the concentration- and endothelium-dependent relaxation of isolated HSV. Vasorelaxation to NaHS probably involves activation of NO/cGMP/PKG pathway and partially prostacyclin. In addition, different K+ channels subtypes, especially SKCa and IKCa , as well as BKCa and KATP channels in high concentrations of NaHS, probably participate in the NaHS-induced vasorelaxation.

Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft.

Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. The present study was undertaken to assess the vasorelaxant effect of procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms. Procyanidin B2 relaxed phenylephrine-induced contraction of HSV rings in concentration-dependent manner. The relaxation was dependent on the presence of endothelium and was strongly affected by l-NAME, hydroxocobalamin or ODQ, the inhibitors of NO/cGMP pathway. Indomethacin significantly affected only the relaxation produced by the highest concentrations of procyanidin B2. Apamin and TRAM-34 combination, in the presence of l-NAME and indomethacin, did not additionally decreased procyanidin B2-induced relaxation. In the presence of K+ channel blockers, relaxation induced by procyanidin B2 was partially attenuated by 4-aminopyridine, significantly inhibited by glibenclamide and almost abolished by iberiotoxin. Procyanidin B2 also relaxed the contractions induced by phenylephrine or caffeine in Ca2+-free solution. Finally, nifedipine slightly, while thapsigargin strongly antagonized HSV relaxation. Our results indicate that procyanidin B2 induces endothelium-dependent relaxation of HSV, which results primarily from stimulation of NO production, as well K+ channels opening, especially BKCa, and partially KATP and KV. Regulation of the intracellular Ca2+ release and inhibition of Ca2+ influx probably contribute to procyanidin B2-induced relaxation.

A prospective, single-blind, randomized, phase III study to evaluate the safety and efficacy of Fibrin Sealant Grifols as an adjunct to hemostasis compared with manual compression in vascular surgery.

OBJECTIVE: New formulations and applications of hemostatic adjuncts such as fibrin sealant (FS) to support local hemostasis and sutures continue to be developed. In a pivotal, confirmatory, controlled, prospective, single-blinded, randomized, multicenter phase III clinical trial, the efficacy and safety of FS Grifols during vascular surgeries were evaluated. METHODS: Patients undergoing a nonemergency, open, peripheral vascular surgical procedure with moderate arterial bleeding were recruited. In an initial preliminary part of the study, all patients were treated with FS Grifols. In a subsequent primary part, patients were randomized (2:1) to FS Grifols or manual compression (MC). The primary efficacy end point was the proportion of the primary part patients achieving hemostasis by 4 minutes after the start of treatment. Cumulative proportion and time to hemostasis were secondary efficacy end points. Safety end points (in pooled preliminary and primary parts) included adverse events (AEs), vital signs, physical assessments, clinical laboratory tests, viral markers, and immunogenicity. RESULTS: The primary efficacy end point was met by 76.1% of patients (83/109) for the FS Grifols group versus 22.8% of patients (13/57) for the MC group (P < .001). The cumulative proportion of patients at 5, 7, and 10 minutes was 80.7%, 84.4%, and 88.1%, respectively, in the FS Grifols treatment group, and 28.1%, 35.1%, and 45.6% in the MC treatment group (P < .001). The median time to hemostasis was shorter in the FS Grifols group (4 minutes vs ≥10 minutes in the MC group; P < .001). The nature of AEs reported were those expected in the study patient profile. The percentage of patients experiencing treatment-emergent AEs were similar in both the FS Grifols (pooled n = 59 + 109) and MC groups (81.0% and 77.2%, respectively), most recurrent being procedural pain (34.5% and 36.8%, respectively) and pyrexia (11.3% and 10.5%, respectively). CONCLUSIONS: FS Grifols was superior in efficacy and similar in safety to MC as an adjunct local hemostatic agent in patients undergoing open vascular surgeries.

Surgical Treatment of Proximal Segmental Occlusion of the Internal Carotid Artery.

PURPOSE: To present the feasibility, safety, and efficacy of carotid endarterectomy in patients with type II internal carotid artery occlusions, including the long-term outcomes. METHODS: From March 2008 to August 2015, 74 consecutive patients (48 men with a mean age of 65.1 ± 8.06 years) underwent carotid endarterectomy because of internal carotid artery (ICA) segmental occlusions. These were verified with preoperative carotid duplex scans (CDS) and CT angiography (CTA). Also, brain CT scanning was performed in all these patients. The indication for treatment was made jointly by a vascular surgeon, neurologist, and an interventional radiologist in a multidisciplinary team (MDT) context. After successful treatment, all the patients were followed-up at 1, 3, 6, and 12 months, then every 6 months thereafter. RESULTS: The most common symptom at presentation was transient ischaemic attack (TIA) in 49 patients (66.2%), followed by stroke in the past six months in the 17 remaining patients (23%). Revascularisation of the ICA with endarterectomy techniques was performed successfully in all the patients with an average clamp time of 11.9 min. All the procedures were performed under general anaesthesia in combination with a superficial cervical block. The early complication rate was 8.1% and included two cardiac events (2.7%) (one rhythm disorder and one acute coronary syndrome), three TIAs (4.1%), and one intracerebral hemorrhage (1.3%). Only one patient with the intracerebral hemorrhage died 5 days after surgery giving a postoperative mortality of 1.3% for this series. During the follow-up period (mean 50.4 ± 31.3 months), the primary patency rates at 1, 3, 5, and 7 years were 98.4%, 94.9%, 92.9%, and 82.9%, respectively. Likewise, the survival rates were 98.7%, 96.8%, 89%, and 77.6%, respectively. Ultrasound Doppler controls during follow-up detected 8 ICA restenoses; however, only 3 of these patients required further endovascular treatment. CONCLUSIONS: Carotid endarterectomy of internal carotid artery (ICA) segmental occlusion is a safe and effective procedure associated with acceptable risk and good long-term results. Therefore, the current guidelines which do not recommend carotid endarterectomy in this patient group should be reassessed, with the requirement for ongoing large-scale randomized controlled trials to compare CEA with best medical therapy in this patient cohort.

Scoring system to predict early carotid restenosis after eversion endarterectomy by analysis of inflammatory markers.

BACKGROUND: Inflammation is one of the mechanisms that leads to carotid restenosis (CR). The aim of this study was to examine the influence of increased values of inflammation markers (high-sensitivity C-reactive protein [hs-CRP], C3 complement, and fibrinogen) on CR development after eversion carotid endarterectomy (CEA). METHODS: A consecutive 300 patients were included in the study, in which eversion CEA was performed between March 1 and August 1, 2010. Demographic data, atherosclerosis risk factors, comorbidities, and ultrasound plaque characteristics were listed in relation to potential risk factors for CR. Serum concentrations of hs-CRP, fibrinogen, and C3 complement were taken just before surgery (6 hours); 48 hours after CEA; and during regular checkups at 1 month, 6 months, 1 year, and 2 years. An "inflammatory score" was also created, which consisted of six predictive values of inflammatory markers (hs-CRP just before and just after CEA, fibrinogen just before and just after CEA, and C3 complement just before and just after CEA) with a maximum score of 6 and a minimum score of 0. At every follow-up visit to the outpatient clinic, ultrasound assessment of the carotid artery for restenosis was done. RESULTS: Our results showed an increased risk of early CR within 1 year in patients with increased hs-CRP before CEA (6 hours) and increased fibrinogen 48 hours after surgery and in patients not taking aspirin after CEA. Sex was determined to be an independent predictor of CR, with female patients having a higher risk (P = .002). Male patients taking aspirin with an inflammatory score >2 had an increased risk for restenosis compared with male patients with inflammatory score <2. Not taking aspirin after CEA and fibrinogen (48 hours) were the strongest predictors, and the Fisher equation incorporating these predictors was used to predict CR. A computer program was created to calculate whether the patient was at high or low risk for CR by selecting whether the patient was taking aspirin (yes or no) and whether fibrinogen was increased 48 hours after CEA (yes or no) and to display the recommended therapeutic algorithm consisting of aspirin, clopidogrel, cilostazol, and statins. CONCLUSIONS: Increased hs-CRP before CEA, increased fibrinogen 48 hours after CEA, and not taking aspirin were the main predictors of early CR. With the clinical implementation of the Fisher equation, it is possible to identify patients at high risk for early CR and to apply an aggressive therapeutic algorithm, finally leading to a decreased CR rate.

(-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels.

In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K+ , whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca2+ -free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca2+ -ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive KV channels, BKCa channels, and at least partly, KATP channels. In addition, not only the inhibition of extracellular Ca2+ influx, but regulation of the intracellular Ca2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca2+ -ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.

A Novel Antegrade Approach for Simultaneous Carotid Endarterectomy and Angioplasty of Proximal Lesions in Patients with Tandem Stenosis of Supraaortic Arch Vessels.

BACKGROUND: To date, all published studies analyzing simultaneous treatment of carotid and proximal atherosclerotic lesions are describing retrograde approach and several technical variations. In the presented study, for the first time, antegrade approach is described for simultaneous carotid endarterectomy (CEA) and associated brachiocephalic trunk (BCT) or common carotid artery (CCA) angioplasty in the hybrid operating room. METHODS: From January 2012 till January 2016, antegrade hybrid procedures were performed in 18 patients. All patients were admitted to our institute for elective supraaortic arch multidetector computed tomography angiography when significant simultaneous proximal and distal supraaortic arch lesions were revealed. After surgical exposure of carotid arteries, proximal lesions were crossed by antegrade approach. Prior to stent placement, internal carotid artery (ICA) is clamped at its origin with the guidewire placed in the external carotid artery (ECA). After primary stenting and control arteriography, CCA and ECA are clamped and the ICA clamp moved more distally. An arteriotomy is performed in the CCA, with flushing of possible debris and thrombus before performance of the eversion CEA, once again flushing before completion of the anastomosis. Follow-up ranged from 6 to 36 months with average follow-up of 22.15 ± 11.31 months. RESULTS: All procedures went uneventfully. Out of 18 patients, 11 were males and 7 females, mean age 66.6 ± 3.82 years. In 10 patients (55.5%), simultaneous CEA and CCA angioplasty was performed, in 7 patients (38.9%) CEA and BCT angioplasty, and in 1 patient (5.5%) tubular graft interposition between the CCA and the ICA and CCA angioplasty. In 6 patients (33.3%), CCA/BCT balloon angioplasty alone was performed simultaneously with CEA. None of the patient had postoperative transient ischemic attack, stroke, hematoma, dissection, myocardial infarction, or ischemia in the early postoperative period and during the follow-up. There were no lethal outcomes, neither in the early postoperative course nor during the follow-up. CONCLUSIONS: Antegrade approach for simultaneous treatment of proximal CCA/BCT and distal carotid lesions with temporary ICA clamping is safe and feasible procedure that should be thought of in the future in addition to already described retrograde approach.

Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal mammary artery.

The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations. Among K+ channel blockers, iberiotoxin, a selective blocker of large conductance Ca2+-activated K+ channels (BKCa), abolished procyanidin B2-induced relaxation, glibenclamide, a selective ATP-sensitive K+(KATP) channels blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage-gated K+(KV) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca2+-activated K+(IKCa) channels, slightly reduced maximal relaxation of HIMA. Further, procyanidin B2 relaxed contraction induced by phenylephrine in Ca2+-free Krebs solution, but had no effect on contraction induced by caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, significantly reduced relaxation of HIMA produced by procyanidin B2. These results demonstrate that procyanidin B2 produces endothelium-dependent relaxation of HIMA pre-contracted by phenylephrine. This effect is primarily the result of an increased NO synthesis and secretion by endothelial cells and partially of prostacyclin, although it involves activation of BKCa and KATP, as well as KV and IKCa channels in high concentrations of procyanidin B2.

Negative-pressure wound therapy for deep groin vascular infections.

Introduction: Infection of synthetic graft in the groin is a rare but devastating complication. When it occurs, several possibilities of treatment are available. Extra-anatomic reconstruction and in-situ implantation of new, infection resistant grafts are associated with high mortality and morbidity. Therefore, more conservative approach is needed in some cases. Negative-pressure wound therapy is one of the options in treating such patients. Objective: The aim of this study was to assess the outcome for deep groin vascular graft infection treated with negative-pressure wound therapy. Methods: Seventeen patients (19 wounds), treated for Szilagyi grade III groin infections between October 2011 and June 2014, were enrolled into this observational study. Results: Majority of the wounds (11/19) were healed by secondary intention, and the rest of the wounds (8/19) were healed by primary intention after initial negative-pressure wound therapy and graft substitution with silver-coated prostheses or autologous artery/vein implantation. No early mortality was observed. Minor bleeding was observed in one patient. Reinfection was noted in three wounds. Only one graft occlusion was noted. Late mortality was observed in three patients. Conclusion: Negative-pressure wound therapy seems to be safe for groin vascular graft infections and comfortable for both patient and surgeon. However, the rate of persistent infection is high. This technique, in our opinion, can be used as a "bridge" from initial wound debridement to definitive wound management, when good local conditions are achieved for graft substitution, either with new synthetic graft with antimicrobial properties or autologous artery/vein. In selected cases of deep groin infections it can be used as the only therapeutic approach in wound treatment.

Massive necrotizing fasciitis following bellow-knee arterial surgery - A therapeutic challenge.

INTRODUCTION: Necrotizing fasciitis is a rare, progressive bacterial infection of superficial fascia followed by secondary subcutaneous tissue necrosis. We pressented a patient with massive fulminant lifethreatening necrotising fasciitis after bellow-knee femoro-popliteal vein bypass grafting successfully treated by antibiotics, surgical debridement and final skin reconstruction using the Tierch method. CASE REPORT: A 61-year-old patient was admitted to the Vascular Surgery Clinic for below-knee femoro-popliteal bypass grafting. He complained of intermittent claudication in the left leg after 50 m, ankle brachial indexes were 0.45 on the left and 1.0 on the right side. Femoropopliteal below-knee bypass grafting was done using the autologous great saphenous vein. In the very next day, initial signs of skin infection appeared including local inflammation, erythema, swelling and cellulitis restricted to saphenectomy site. These changes had rapidly spread in the following days on the deep tissue of the whole upper and lower leg, including the groin and with clinical signs of life-threatening systemic infection. Immediate surgical debridement was done followed by extensive wound packing and wide spectrum antibiotics administration for the next 33 days when final skin reconstruction by the Tierch method was performed. Interesting point is that this entire time wound swab was sterile. CONCLUSION: In the presented case immediate surgical debridement, wide spectrum antibiotics administration and consistent wound packing gave satisfactory results in this life-threatening systemic infection. Wound swab is not always a reliable indicator of the infection while clinical findings and surgeons' experience are of great significance in rapid reaction to this rare surgical complication.

Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin.

Evidences have suggested that flavanol compound (-)-epicatechin is associated with reduced risk of cardiovascular diseases. One of the mechanisms of its cardioprotective effect is vasodilation. However, the exact mechanisms by which (-)-epicatechin causes vasodilation are not yet clearly defined. The aims of the present study were to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human internal mammary artery (HIMA) and to determine the mechanisms underlying its vasorelaxation. Our results showed that (-)-epicatechin induced a concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Among the K(+) channel blockers, 4-aminopyridine (4-AP) and margatoxin, blockers of voltage-gated K(+) (KV) channels, and glibenclamide, a selective ATP-sensitive K(+) (KATP) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca(2+)-activated K(+) channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80mM K(+), (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca(2+)-free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, slightly antagonized (-)-epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. These results suggest that (-)-epicatechin induces strong endothelium-independent relaxation of HIMA pre-contracted by phenylephrine whilst 4-AP- and margatoxin-sensitive KV channels, as well as BKCa and KATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca(2+), interfere with intracellular Ca(2+) release and re-uptake by the sarcoplasmic reticulum.

Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts.

As we previously demonstrated the role of different K(+) channels in the action of nicorandil on human saphenous vein (HSV) and human internal mammary artery (HIMA), this study aimed to analyse the contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K(+) channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K(+) (KATP) channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K(+) (KV) channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca(2+)-activated K(+) (BKCa) channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of KV channels in HSV is probably due to GC activation and increased levels of cGMP.

A rare case of large isolated internal iliac artery aneurysm with ureteral obstruction and hydronephrosis: Compression symptoms are limitation for endovascular procedures.

INTRODUCTION: In this report, we aim to present a rare case of isolated internal iliac artery aneurysm with associated left ureteric obstruction and consequent hydronephrosis. CASE REPORT: A 66-year-old male patient was admitted for occasional pain in the lower back that appeared one month earlier. CT arteriography revealed isolated internal iliac artery (diameter 99 mm) with ureteral obstruction, hydroureter and left kidney hydronephrosis occurrence. Aneurysm was resected, after six months the patient was doing well. Bearing in mind that 77% of the patients with isolated internal iliac artery have symptoms caused by aneurysmal compression on adjacent organs, we wanted to highlight that despite the amazing expansion of endovascular procedures in the last decades, its therapeutic effect in isolated internal iliac artery's treatment is to a great extent limited since compression symptoms cannot be solved. CONCLUSION: Open surgery remains the gold standard for isolated internal iliac artery's treatment considering significant limitations of endovascular procedures due to the inability to eliminate problems caused by compression.

Thrombolysis of occluded femoropopliteal graft with locally delivered human plasmin.

INTRODUCTION: Acute lower limb ischemia results from thrombosis or embolization of diseased native artery or previously implanted bypass graft. When this occurs, several options are available to restore blood flow: catheter-directed thrombolysis, mechanical thrombectomy or open surgery. Fundamental reasons to apply percutaneous interventions are avoiding open procedures in high risk patients, and avoiding difficult dissection through scar tissue. CASE OUTLINE: A 67-year-old male was admitted at our Institution for critical limb ischemia. After performed angiography the diagnosis of occluded femoropopliteal graft was established. Occlusion was resolved by catheter-directed thrombolysis with plasmin. Culprit lesions were treated by angioplasty. CONCLUSION: Our patient underwent a successful thrombolysis of occluded femoropopliteal graft with locally-delivered human plasmin.

["Blue-toe" syndrome as a possible complication of the abdominal aortic aneurysm: a report of two cases].

INTRODUCTION: Severe extremity ischemia and the presence of the"blue-toe"syndrome are rarely the first complications of the present abdominal aortic aneurysm.We report two interesting cases of this rare entity. OUTLINE OF CASES: A 61-year-old man presented with the rest pain of his toes accompanied with digital ischemia of both feet. Physical examination confirmed regular arterial pulses at lower extremities accompanied with palpable pulsate mass in the abdomen. Vascular ultrasound and multidetector tomography (MDCT) of blood vessels revealed small abdominal aortic aneurysm (37 mm in diameter), filled with the irregular, ulcerated, heterogeneous thrombotic masses. Aneurysm sac resection was performed with an aorto-bi-iliac bypass reconstruction. A week later, it was mandatory to amputate the fifth toe on the left foot because of the advanced gangrenous process.The second case was a 77-year-old woman with 7-day history of severe feet pain. Abdominal examination revealed pulsatile mass paraumbilical to the left. Performed abdominal ultrasonography and MDCT angiography confirmed coexistence of the infrarenal aortic aneurysm, 40.5 mm in diameter, covered by significant mobile mural thrombus and ulcerations. Surgical reconstruction was mandatory and patient underwent aneurysm sac resection and aortobifemoral reconstruction. CONCLUSION: Embolic phenomenon and peripheral embolic occlusion from the mural thrombus within the abdominal aortic aneurysm are relatively rare events, but associated with tissue loss.Thorough diagnostic examinations and prompt management are required regardless of the aneurysm size once these signs occurred.

Primary repair of internal carotid artery aneurysm secondary to kinking and cystic medial degeneration.

INTRODUCTION: In this report, we aim to present a very rare case of internal carotid artery (ICA) aneurysm secondary to kinking and cystic medial degeneration. CASE REPORT: A 66-year-old female patient was admitted to our institution for multidetector computed tomography (MDCT) angiography of supra-aortic trunks. On admission, she complained of occasional dizziness; 2 months earlier ascending aorta reconstruction was done for aneurysmal disease. Color Doppler ultrasonography and MDCT arteriography revealed significant right ICA kinking associated with large aneurysm, 24.6 × 24.5 mm(2) in diameter. Aneurysm resection was done followed by ICA reconstruction by end-to-end anastomosis. Pathohistological findings of aneurysmal sac revealed cystical medial degeneration with inflammatory infiltrate mostly consisting of lymphocytes and fibrovascular proliferation. CONCLUSION: This is the first case that describes mutual contribution of cystic medial degeneration and ICA kinking in carotid aneurysm disease etiology successfully treated by aneurysm resection.

The value of the sagittal-oblique MRI technique for injuries of the anterior cruciate ligament in the knee.

BACKGROUND: Complete rupture of the anterior cruciate ligament (ACL) does not represent a diagnostic problem for the standard magnetic resonance (MR) protocol of the knee. Lower accuracy of the standard MR protocol for partial rupture of the ACL can be improved by using additional, dedicated MR techniques. The study goal was to draw a comparison between sagittal-oblique MR technique of ACL imaging versus flexion MR technique of ACL imaging and, versus ACL imaging obtained with standard MR protocol of the knee. PATIENTS AND METHODS: In this prospective study we included 149 patients who were referred to magnetic resonance imaging (MRI) examination due to knee soft tissues trauma during 12 months period. MRI signs of ACL trauma, especially detection of partial tears, number of slices per technique showing the whole ACL, duration of applied additional protocols, and reproducibility of examination were analysed. RESULTS: Accuracy of standard MRI protocol of the knee comparing to both additional techniques is identical in detection of a complete ACL rupture. Presentations of the partial ruptures of ACL using flexion technique and sagittal-oblique technique were more sensitive (p<0.001) than presentation using standard MR protocol. There was no statistically significant difference between MRI detection of the ruptured ACL between additional techniques (p> 0.65). Sagittal-oblique technique provides a higher number of MRI slices showing the whole course of the ACL and requires a shorter scan time compared to flexion technique (p<0.001). CONCLUSIONS: Both additional techniques (flexion and sagittal-oblique) are just as precise as the standard MR protocol for the evaluation of a complete rupture of the ACL, so they should be used in cases of suspicion of partial rupture of the ACL. Our study showed sagittal-oblique technique was superior, because it did not depend on patient's ability to exactly repeat the same external rotation if standard MR protocol was used or to repeat exactly the same flexion in flexion MR technique in further MR examinations. Sagittal-oblique technique does not require the patient's knee to be repositioned, which makes this technique faster. We propose this technique in addition to the standard MR protocol for detection of partial ACL tears.