Acute Vascular Occlusion Research Articles

Detection of flap tissue ischemia in a rat model: Real-time monitoring of changes in oxygenation and perfusion through injectable biosensors

BackgroundThe success of surgical flaps is improved by timely correction of vascular compromise. Current monitoring methods are labor or cost intensive or have limited clinical benefit. We hypothesize that injectable oxygen sensors can identify acute vascular compromise. The purpose of this study was to use a long-term, real-time method of tissue oxygenation detection in a rat flap model with vascular manipulation. MethodsSensors incorporated benzo-porphyrin dye into a microporous hydrogel and were injected intradermally 1 day before flap elevation. Inspired oxygen was modulated between 100% and 12% to confirm sensor O2 sensitivity. Eight random flaps (4 cm wide, 8 cm long) were elevated. Sensor and clinical observation to temporary clamping of the flap vascular pedicle was recorded. Sodium fluorescein in saline was injected intraperitoneally on postoperative days 0, 3, and 7 with subsequent perfusion area analysis. ResultsTissue oxygen tension measurements reflected the changes in inspired oxygen levels. Clinical observation of the flaps did not show any significant change in color or temperature with pedicle clamping. However, clamping of the pedicle resulted in a significant decrease in sensor tissue oxygen tension within 70 seconds. ConclusionOxygen monitoring of myocutaneous flaps is sensitive and can detect acute vascular occlusion. This technique is faster than current methods and offers a cost-effective and accurate means of monitoring surgical tissues.

Diffusion-Weighted Imaging, MR Angiography, and Baseline Data in a Systematic Multicenter Analysis of 3,301 MRI Scans of Ischemic Stroke Patients-Neuroradiological Review Within the MRI-GENIE Study.

Background: Magnetic resonance imaging (MRI) serves as a cornerstone in defining stroke phenotype and etiological subtype through examination of ischemic stroke lesion appearance and is therefore an essential tool in linking genetic traits and stroke. Building on baseline MRI examinations from the centralized and structured radiological assessments of ischemic stroke patients in the Stroke Genetics Network, the results of the MRI-Genetics Interface Exploration (MRI-GENIE) study are described in this work.Methods: The MRI-GENIE study included patients with symptoms caused by ischemic stroke (N = 3,301) from 12 international centers. We established and used a structured reporting protocol for all assessments. Two neuroradiologists, using a blinded evaluation protocol, independently reviewed the baseline diffusion-weighted images (DWIs) and magnetic resonance angiography images to determine acute lesion and vascular occlusion characteristics.Results: In this systematic multicenter radiological analysis of clinical MRI from 3,301 acute ischemic stroke patients according to a structured prespecified protocol, we identified that anterior circulation infarcts were most prevalent (67.4%), that infarcts in the middle cerebral artery (MCA) territory were the most common, and that the majority of large artery occlusions 0 to 48 h from ictus were in the MCA territory. Multiple acute lesions in one or several vascular territories were common (11%). Of 2,238 patients with unilateral DWI lesions, 52.6% had left-sided infarct lateralization (P = 0.013 for χ2 test).Conclusions: This large-scale analysis of a multicenter MRI-based cohort of AIS patients presents a unique imaging framework facilitating the relationship between imaging and genetics for advancing the knowledge of genetic traits linked to ischemic stroke.

4511 Bio-Compatible Implantable Oxygen Sensor Technology with Real-Time Monitoring of Surgical Flaps and Reimplantation

OBJECTIVES/GOALS: Current surgical flap and replantation monitoring techniques have limitations in detecting the pathologic state, calibration and cost-to-patient issues. Our hypothesis is that novel implantable oxygen sensors can provide a more efficient, accurate, and reliable monitoring of tissue oxygenation. METHODS/STUDY POPULATION: Experimental sensors were used with an exogenous remote used as a reader once implanted (Fig. 1) A rat tissue perfusion model with three regions of an SIEA flap as well as into adjacent control sites was made (Tip, Middle, and Base) Blood flow was greatest at the base, diminishing towards the Tip, thus creating a perfusion gradient. Changes in tissue oxygen tension PO2 were estimated by the steady-state fluorescence of the optical sensors using an IVIS imaging system. The sensors were used to collect data from days 0, 3, and 7 as a reading of Tissue Oxygen Tension (TOT) with ANOVA used to assess for statistical significance in blood oxygen data with respect to relative perfusion status. RESULTS/ANTICIPATED RESULTS: Inspired FiO2 was decreased from 100% to 12% with a corresponding change in the TOT readings from all sensors. (Fig. 2) The tip portion of the flap demonstrated the most profound detection of tissue necrosis, with the middle demonstrating the second most necrosis and the base demonstrating the least with correlating TOT sensor readings. (Fig. 3) Acute vascular compromise of the feeding blood vessels in the pedicle was immediately detected within 70 seconds (*p<0.05). (Fig. 4) DISCUSSION/SIGNIFICANCE OF IMPACT: This study introduces and validates a recent technique to monitor acute vascular occlusion, flap viability, and necrosis in the immediate postoperative period in a validated rodent model. Future directions of this novel technology will aim to reproduce these findings in clinical feasibility studies.

Contralateral acute vascular occlusion following revascularization surgery for moyamoya disease.

Revascularization surgery is a safe and effective surgical treatment for symptomatic moyamoya disease (MMD) and has been shown to reduce the frequency of future ischemic events and improve quality of life in affected patients. The authors sought to investigate the occurrence of acute perioperative occlusion of the contralateral internal carotid artery (ICA) with contralateral stroke following revascularization surgery, a rare complication that has not been previously reported. This study is a retrospective review of a prospective database of a single surgeon's series of revascularization operations in patients with MMD. From 1991 to 2016, 1446 bypasses were performed in 905 patients, 89.6% of which involved direct anastomosis of the superficial temporal artery (STA) to a distal branch of the middle cerebral artery (MCA). Demographic, surgical, and radiographic data were collected prospectively in all treated patients. Symptomatic contralateral hemispheric infarcts occurred during the postoperative period in 34 cases (2.4%). Digital subtraction angiography (DSA) was performed in each of these patients. In 8 cases (0.6%), DSA during the immediate postoperative period revealed associated new occlusion of the contralateral ICA. In each of these cases, revascularization surgery involved direct anastomosis of the STA to an M4 branch of the MCA. Preoperative DSA revealed moderate (n = 1) or severe (n = 3) stenosis or occlusion (n = 4) of the ipsilateral ICA and mild (n = 2), moderate (n = 4), or severe (n = 2) stenosis of the contralateral ICA. The baseline Suzuki stage was 4 (n = 7) or 5 (n = 1). The collateral supply originated exclusively from the intracranial circulation in 4/8 patients (50%), and from both the intracranial and extracranial circulation in the remaining 50% of patients. Seven (88%) of 8 patients improved symptomatically during the acute postoperative period with induced hypertension. The modified Rankin Scale (mRS) score at discharge was worse than baseline in 7/8 patients (88%), whereas 1 patient had only minor deficits that did not affect the mRS score. At the 3-year follow-up, 3/8 patients (38%) were at their baseline mRS score or better, 1 patient had significant disability compared with preoperatively, 2 patients had died, and 1 patient was lost to follow-up. Three-year follow-up is not yet available in 1 patient. Acute occlusion of the ICA on the contralateral side from an STA-MCA bypass is a rare, but potentially serious, complication of revascularization surgery for MMD. It highlights the importance of the hemodynamic interrelationships that exist between the two hemispheres, a concept that has been previously underappreciated. Induced hypertension during the acute period may provide adequate cerebral blood flow via developing collateral vessels, and good outcomes may be achieved with aggressive supportive management and expedited contralateral revascularization.

Inhibin B level changes during the follicular phase in rats with unilateral ovarian torsion

Objective: To investigate the association between duration of ovarian torsion and levels of serum inhibin B in an animal model. Materials and Methods: An animal model prospective study was conducted in a tertiary referral hospital and chemical pathology institute. Nineteen female Lewis rats were divided to four groups. In the first group, the control group, laparotomies alone were performed. In groups 2-4 laparotomies and right ovarian torsion for 720 degrees with fixation of the adnexa to the parietal peritoneum were performed. Blood samples were taken from the rat groups at 12, 24, and 36 hours after laparotomy. Inhibin B levels were measured by ELISA. Results: Serum mean ± SD inhibin B level in the control rats during the beginning of the metesterus, 12, 24, and 36 hours later were 108.4 ± 43.6, 129.5 ± 49.3, 99.07 ± 60.50, and 91.58 ± 27.74 pg/ml, respectively. Inhibin B levels in the control group increased 12 hours after the beginning of the metesterus, whereas in the study group, a decline in inhibin B levels was found at the same time. This difference was significant (p = 0.05). Inhibin B levels at 24 and 36 hours from the beginning of the metestrus did not show statistical difference. Conclusions: Unilateral ovarian torsion in rats changed the pattern of inhibin B secretion at the beginning of the metesterus and was associated with a significant decrease in inhibin B serum levels. This observation, following acute ovarian vascular occlusion, is probably due the effects of ischemia on hormonal regulation during the early follicular phase.

Anticoagulation in Atherosclerotic Disease.

The prevention of atherothrombotic events is an essential therapeutic goal in the treatment of patients with arteriosclerotic diseases. After plaque rupture, a rapidly growing thrombus can lead to acute vascular occlusion and thus heart attack, stroke or limb ischaemia. The acute therapy combines anticoagulation and platelet inhibition. However, the only available therapy so far in the primary and secondary prevention of stable patients is the platelet inhibitors aspirin and clopidogrel. Despite the use of antiplatelet therapies, including aspirin and P2Y12-receptor antagonists, some patients with artery disease continue to experience recurrent cardiovascular ischaemic events due to excessive thrombin generation beyond the acute period. As a result, studies have tested non-vitamin K antagonist oral anticoagulants (NOACs), specifically the factor Xa inhibitors, either alone or in combination with antiplatelet therapy, in the management of arterial disease. For the first time, the COMPASS study investigated low-dose anticoagulation in stable coronary heart disease or peripheral arterial disease. The addition of 2 × 2.5 mg rivaroxaban to long-term aspirin therapy not only prevented cardiovascular death, myocardial infarction and stroke, but even reduced all-cause mortality by a relative 18% after a mean follow-up of 23 months. This benefit came at the expense of more gastrointestinal bleeding, which might be reduced by the addition of a proton pump inhibitor (investigations are ongoing). Interestingly, however, there was no increase in fatal or intracranial haemorrhages. Therefore, a new standard therapy for high-risk patients with atherosclerotic disease may become available in the near future.

Paracentral Acute Middle Maculopathy and the Ischemic Cascade Associated With Retinal Vascular Occlusion

To analyze the spectrum of ischemia associated with paracentral acute middle maculopathy (PAMM) in eyes with acute retinal vascular occlusion and to describe an ischemic cascade. A retrospective observational case series. Patients presenting with PAMM secondary to acute retinal vascular occlusion were identified. Analysis of multimodal imaging was performed at baseline and at follow-up visits to elucidate the patterns and progression of ischemia within the retinal layers. Multimodal retinal imaging from 16 eyes of 16 patients with acute retinal vascular occlusion associated with PAMM was studied. Analysis of en face optical coherence tomography (OCT) segmentation of the inner nuclear layer (INL) identified distinct patterns of PAMM correlating with the severity of ischemia and not the type of occlusion. A perivenular fern-like PAMM pattern was associated with better visual outcomes (average final visual acuity was 20/25). This pattern was noted to sequentially progress in 2 cases to a diffuse globular PAMM pattern in the INL, or to a pattern of ischemia involving both the middle and inner retinal layers with commensurate vision loss. Globular patterns of PAMM or ischemia involving both the middle and inner retina correlated with poorer visual outcomes (average final visual acuity was counting fingers at 5.5 ft). These various patterns of ischemia developed in eyes with retinal vascular occlusions in which blood flow through the retinal capillary plexuses was present but was significantly reduced and delayed. This study describes OCT findings suggestive of an ischemic cascade in eyes with retinal vascular occlusion. The middle retina at the level of the deep capillary plexus, especially at the venular pole, may be more vulnerable to ischemic injury.

Oesophageal necrosis after thoracic endovascular aortic repair: a minimally invasive endovascular approach-a dramatic complication.

There are few cases in the literature reporting dysphagia caused by oesophageal compression by the aorta due to acute or chronic aortic pathology. This type of dysphagia is called dysphagia aortica. Thoracic endovascular aortic repair is nowadays the treatment of choice for anatomically suitable patients experiencing complicated Type B aortic dissection. Oesophageal necrosis is a rare but fatal complication following thoracic endovascular aortic repair. Extrinsic oesophageal compression by the thrombosed aneurysmal sac, a mediastinal haematoma or extensive thrombosis in the false lumen of a dissected aorta and acute vascular occlusion of the oesophageal supply are possible mechanisms. When oesophageal necrosis is suspected, endoscopic examination and computed tomography imaging should be performed repeatedly. Oesophagoscopy will confirm the diagnosis revealing a black, diffusely necrotic and ulcerated oesophageal mucosa. It is critical to intervene before full-thickness oesophageal wall necrosis and mediastinitis occur. Guidelines are absent because of the rarity of this complication. Moreover, lack of a large series does not permit the establishment of guidelines either. However, oesophagectomy of the impaired oesophagus is the only chance for survival. Unfortunately, survival rates are disappointing. Prevention and awareness is the cornerstone of success. Early endoscopic examination when oesophageal necrosis is suspected due to even minimal symptoms will detect this fatal menace on time.

Analysis of trends and prospects regarding stents for human blood vessels

BackgroundThe purpose of this paper is to provide technology trends and information regarding market and prospects in stents used for human blood vessels in Korea and the world.A stent is a medical device in the form of a cylindrical metal net used to normalize flow when blood or other bodily fluids such as biliary fluids are obstructed in blood vessels, gastrointestinal tracts, etc. by inserting the stent into a narrowed or clogged area. Stents are classified into vascular and non-vascular stents. The coronary artery stent is avascular stent that is used for coronary atherosclerosis.The demand is increasing for stents to treat diseases such as those affecting the heart and blood vessels of elderly and middle-aged patients. Due to the current shift in the demographic structure caused by an aging society, the prospect for stents seems to be very bright.The use of a stent designed to prevent acute vascular occlusion and restenosis, which is a side effect of conventional balloon angioplasty, has rapidly become popular because it can prevent acute complications and improve clinical outcomes. Since the initial release of this stent, there have been significant developments in its design, the most notable of which has been the introduction of drug-eluting stents (DES). Bioresorbable scaffolds (BRS) have the potential to introduce a paradigm shift in interventional cardiology, a true anatomical and functional “vascular restoration” instead of an artificial stiff tube encased by a persistent metallic foreign body.MethodsData for this research were gathered from primary and secondary sources as well as the databases of the Korea Institute of Science Technology Information (KISTI) located in Seoul, Korea like KISTI Market Report. The sources used for primary research included the databases available from the Korea Institute of Science Technology Information, past industry research services/studies, economic and demographic data, and trade and industry journals. Secondary research was used to supplement and complement the primary research. Interviews were conducted with physicians and surgeons from the key hospitals and senior sale/marketing managers from stent product suppliers in South Korea.ResultsThe global stent market is estimated at US $ 7.98 billion in 2016 and is expected to grow at a Compound Annual Growth Rate (CAGR) of 3.8% over the next 5 years. As of 2016, the global market for vascular stents is estimated at $ 7.22 billion, with coronary artery stents accounting for 67.3% of the vascular stent market. Among the coronary artery stents, BRS is notably expected to grow at an annual average rate of 8.8% by 2020, but the global adoption rate of BRS remains low at present. In the Korean market, stents for blood vessels account for most of the market, and the market size of stents for blood vessels in Korea was estimated to be 145 billion won as of 2016.ConclusionsIn comparison to the sales growth rate of other medical devices, the future stent technology market is judged to be higher in growth potential.

Percutaneous Aspiration Embolectomy in the Treatment of Acute Arterial Embolic Infrainguinal Vascular Occlusion

Background: Since its introduction, percutaneous aspiration embolectomy (PAE) has become a well-known, widely accepted and frequently applied technique for the treatment of acute arterial embolic infrainguinal vascular occlusion in lower limb ischemia. Purpose: To evaluate the technical and clinical success of sole percutaneous aspiration embolectomy (PAE) for the treatment of acute arterial embolic infrainguinal vascular occlusion. Material and Methods: During a period of 7 years, 50 patients (24 fermale, 48%) with a mean age of 73 (range 53–95) years were identified in whom 54 cases of PAE were performed for the treatment of arterial embolic infrainguinal vascular occlusion. Primary technical success was defined as residual stenosis of <50% in diameter after sole PAE, secondary technical success was defined as residual stenosis of <50% in diameter after PAE and additional percutaneous transluminal angioplasty (PTA) and/or stenting. Clinical outcome parameters (e.g. need for further intervention and/or amputation) were evaluated for the 30-day postinterventional period. Results: The primary technical success rate was 85% (46 of 54 cases). The secondary technical success rate was 96% (52 of 54 cases). Clinical outcome data were achievable in 50 of the 54 cases (93%). In 43 of the 50 patients (86%) there was no need for further intervention within the 30-day postinterventional period. In summary, during this 30-day postinterventional period after PAE amputation was carried out or death occurred in 5 of 50 patients (10%). Conclusion: Minimally invasive PAE is an effective and safe technique for the treatment of acute arterial embolic infrainguinal vascular occlusion.

Ischemic Proctitis Presenting as Rectal Pain and Bloody Diarrhea with No Apparent Cause

Acute ischemic proctitis is a rare condition usually resulting from severe vascular disease or an acute vascular occlusion. The diagnosis is made on endoscopy, and mortality rates approach 20–40%. Many patients will require a proctectomy as the definitive treatment, especially for gangrenous proctitis. We describe an unusual presentation of acute ischemic proctitis in a patient without preexisting vascular disease or other precipitants. Furthermore, our patient recovered entirely with conservative management and intravenous antibiotics alone. We review the existing literature on ischemic proctitis and highlight the need for future research to better diagnose and manage this rare condition.

Markers of endothelial dysfunction and leucocyte activation in Saudi and non-Saudi haplotypes of sickle cell disease.

Sickle cell disease (SCD) is an autosomal recessive inherited hemoglobinopathy, characterized by chronic hemolysis and recurrent vaso-occlusive crisis (VOC). This study investigates changes in leucocyte subsets and the relationship between cell adhesion molecule expression and disease manifestations in patients during steady state and acute VOC. We compared soluble E-selectin and P-selectin levels in 84 SCD patients, in steady state and during VOC to 84 healthy controls. Using immunophenotyping, we also compared lymphocyte subsets in these three groups. Further, we compared E-selectin and P-selectin levels in patients of Saudi ethnicity to non-Saudi patients, in all three groups. Lymphocyte subsets showed high percentages of total T lymphocytes, T helper and suppressor lymphocytes, B lymphocytes as well as NK cells in patients with SCD during steady state, while B lymphocytes and NK cells were significantly higher during acute VOC crisis. High levels of both soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) markers were demonstrated in the serum of patients with SCD during both steady state and acute VOC. Levels of selectins were significantly higher in acute VOC. The immunophenotypic expression of L-selectin, on leucocytes, was high in SCD both during steady state and during acute VOC in comparison to normal control subjects. There was no significant difference in all three study groups between Saudi and non-Saudi patients. These findings suggest that patients with SCD have increased expression of adhesion molecules: E-selectin and P-selectin, which play an important role in the pathogenesis of VOC. Despite the distinct phenotype of Saudi patients with SCD, there was no significant difference in levels of soluble E-selectin and soluble P-selectin between Saudi and non-Saudi patients in all three groups. While sickle cell disease is a well-recognized state of chronic inflammation, the role of specific adhesion molecules is steadily unraveling. Studies are underway to investigate the potential role of selectin antagonists, for prevention and reversal of acute vascular occlusions in SCD patients.

Vascular complications in plating of the proximal femur: review

Plating of the proximal femur represents a standard fixation method in orthopedic and trauma surgery. Vascular lesions are uncommon but potentially life-threatening. With the increasing number of hip surgery also more of these complications have to be anticipated. The purpose of this study was to evaluate the most common types and locations of vascular lesions after plating of the proximal femur as well as the most important causes. A literature research was undertaken of the English and german literature on vascular complications after plating of the proximal femur following a structured search protocol. 62 cases with vascular compromise after plating of the proximal femur revealed significantly more iatrogenic origin (n=41/62) was observed than lesions caused by fracture fragments (n=11/62) (p=0.0001); most iatrogenic reasons (n=28/62) were related to the insertion of plate screws (PS). Lesions were significantly more often located (57/62) in the deep femoral artery (DFA) system than in other vascular systems (n=5/62) (p=0.0001). Vascular damages represented significantly more often pseudoaneurysms (PA) (42/62) than major lesions in the vessel wall with acute bleeding (17/62) or vascular occlusions (3/62); (p=0.0001). PA cases also revealed a significantly longer diagnostic delay than other lesions (36days vs. 2days, p=0.0064). Among clinical symptoms swelling of the thigh (57/62), local pains (42/62) and anemia (26/62) were most often observed. Swelling and pains were significantly more often reported in PAs (p=0.0338; p=0.0003). Most patients achieved full functional recovery (n=41/62), but over-all complication rate was quite high (n=18/62). Vascular compromise in plate osteosynthesis of the proximal femur affects significantly more often the DFA system and represents most often PA. As the majority of cases revealed iatrogenic origin, a thorough surgical technique and awareness can help to avoid these complications.

MEK1/2 inhibitors reverse acute vascular occlusion in mouse models of sickle cell disease.

In sickle cell disease (SCD), treatment of recurrent vasoocclusive episodes, leading to pain crises and organ damage, is still a therapeutic challenge. Vasoocclusion is caused primarily by adherence of homozygous for hemoglobin S (SS) red blood cells (SSRBCs) and leukocytes to the endothelium. We tested the therapeutic benefits of MEK1/2 inhibitors in reversing vasoocclusion in nude and humanized SCD mouse models of acute vasoocclusive episodes using intravital microscopy. Administration of 0.2, 0.3, 1, or 2 mg/kg MEK1/2 inhibitor to TNF-α-pretreated nude mice before human SSRBC infusion inhibited SSRBC adhesion in inflamed vessels, prevented the progression of vasoocclusion, and reduced SSRBC organ sequestration. By use of a more clinically relevant protocol, 0.3 or 1 mg/kg MEK1/2 inhibitor given to TNF-α-pretreated nude mice after human SSRBC infusion and onset of vasoocclusion reversed SSRBC adhesion and vasoocclusion and restored blood flow. In SCD mice, 0.025, 0.05, or 0.1 mg/kg MEK1/2 inhibitor also reversed leukocyte and erythrocyte adhesion after the inflammatory trigger of vasoocclusion and improved microcirculatory blood flow. Cell adhesion was reversed by shedding of endothelial E-selectin, P-selectin, and αvβ3 integrin, and leukocyte CD44 and β2 integrin. Thus, MEK1/2 inhibitors, by targeting the adhesive function of SSRBCs and leukocytes, could represent a valuable therapeutic intervention for acute sickle cell vasoocclusive crises.

Acute mesenteric ischemia

Acute vascular occlusion within the mesenteric circulation leads to ischemic damage of the corresponding bowel segment, which starts on the mucosal level and progresses transmurally. Report on pathogenesis, clinical picture and treatment of various forms of intestinal ischemia. Analysis of the available literature taking into consideration our own experience. Frequently, predisposing diseases and risk factors are present (e.g., cardiac diseases, hypercoagulability, status post cardiac surgery, circulatory failure, or administration of vasoconstrictive drugs). Acute small bowel ischemia-caused by either mesenteric embolism, mesenteric artery thrombosis, nonocclusive mesenteric ischemia (NOMI) or mesenteric venous thrombosis-represents an acute emergency. If this condition is suspected clinically, the diagnosis must be established immediately by computed tomography of the abdomen with intravenous administration of contrast medium in order to prevent irreversible damage to the small bowel. Medical treatment is supportive. If possible, occluded vessels may be re-opened either by radiologic intervention or surgically. Irreversibly damaged bowel segments must be surgically removed. Ischemic colitis has a benign course in most cases if limited to reversible mucosal damage. The diagnosis is based mainly on colonoscopy and computed tomography findings, and treatment is symptom oriented. Rarely, severe manifestations with a worse prognosis due to considerable comorbidities occur. In such cases, surgical removal of the ischemic bowel is frequently required. Even today, acute mesenteric ischemia is associated with a poor prognosis. To improve survival and to reduce long-term morbidity, a rapid and systematic diagnostic workup is mandatory.

161 Use of colchicine in cardiovascular diseases – a systematic review

Introduction Colchicine, commonly classified as an anti-inflammatory agent, is a mainstay for the treatment of gout and a second-line therapy for other conditions, including pericarditis, familial Mediterranean fever and Behcet’s disease. Recent studies suggest that colchicine may be beneficial in a wide spectrum of cardiovascular diseases. We carried out a systematic review to investigate whether, in randomised controlled trials, colchicine has an effect on the rate of cardiovascular events. Method Controlled clinical studies were searched in BioMedCentral, the Cochrane Collaboration Database of Randomised Trials (CENTRAL), ClinicalTrials.gov, Google Scholar, MEDLINE/PubMed, Scopus and EMBASE provided they focused on whether colchicine had an effect on primary or secondary prevention of cardiovascular events The PubMed search was performed with the term ‘colchicine’ and ‘randomised’. Results From 244 citations, eleven randomised controlled trials were identified, of which seven were double-blind. Four trials focussed on the effects of colchicine on coronary atheroma, three on pericarditis, two on atrial fibrillation, one on both pericarditis and atrial fibrillation and one on chronic heart failure. Altogether, 1360 patients were assigned to control and 1323 to colchicine. One substantial trial (n = 523 followed for a median of 3 years) showed that colchicine 0.5 mg/day reduced vascular events (hazard ratio: 0.33; 95% confidence interval [CI] 0.18 to 0.59; p Meta-analytic pooling showed that colchicine use was associated with a reduced risk of overall cardiovascular events (ACS, in-stent restenosis, postop AF, postop pericardiotomy, postop pericardial effusions, pericarditis and death) with a similar risk of adverse events as placebo. Focussing on the composite of acute vascular occlusion (MI, CVA or CV death), there were 78 events in control groups versus 50 on colchicine. There were 21 deaths in patients assigned to control compared to thirteen assigned to colchicine. Conclusion Long-term prophylaxis with low-dose colchicine appears safe and may be effective for a number of cardiovascular conditions. Whether colchicine can modify the course of coronary artery disease or heart failure, two cardiovascular conditions associated with activation of inflammatory pathways, deserves further investigation.

Short-term inhibition of DPP-4 enhances endothelial regeneration after acute arterial injury via enhanced recruitment of circulating progenitor cells

BackgroundEndothelial injuries regularly occur in atherosclerosis and during interventional therapies of the arterial occlusive disease. Disturbances in the endothelial integrity can lead to insufficient blood supply and bear the risk of thrombus formation and acute vascular occlusion. At present, effective therapeutics to restore endothelial integrity are barely available.We analyzed the effect of pharmacological DPP-4-inhibition by Sitagliptin on endogenous progenitor cell-based endothelial regeneration via the SDF-1α/CXCR4-axis after acute endothelial damage in a mouse model of carotid injury. Methods and ResultsInduction of a defined endothelial injury was performed in the carotid artery of C57Bl/6 mice which led to a local upregulation of SDF-1α expression. Animals were treated with placebo, Sitagliptin or Sitagliptin+AMD3100. Using mass spectrometry we could prove that Sitagliptin prevented cleavage of the chemokine SDF-1α. Accordingly, increased SDF-1α concentrations enhanced recruitment of systemically applied and endogenous circulating CXCR4+ progenitor cells to the site of vascular injury followed by a significantly accelerated reendothelialization as compared to placebo-treated animals. Improved endothelial recovery, as well as recruitment of circulating CXCR4+ progenitor cells (CD133+, Flk1+), was reversed by CXCR4-antagonization through AMD3100. In addition, short-term Sitagliptin treatment did not significantly promote neointimal or medial hyperplasia. ConclusionSitagliptin can accelerate endothelial regeneration after acute endothelial injury. DPP-4 inhibitors prevent degradation of the chemokine SDF-1α and thus improve the recruitment of regenerative circulating CXCR4+ progenitor cells which mediate local endothelial cell proliferation without adversely affecting vessel wall architecture.

Early Graft Loss After Kidney Transplantation: Risk Factors and Consequences.

The increasing use of kidneys from marginal donors may be associated with a higher risk of early graft loss, which is a potentially catastrophic outcome. However, the risk factors and consequences of early graft loss after kidney transplantation have not previously been examined among different donor types. Recipients of kidney-only transplants between January 2002 and April 2012 in our centre who suffered graft loss within 30 days were identified from a prospectively-maintained database. Factors associated with early graft loss were determined by multivariate analysis. Within the study period,1090 patients received a kidney-only transplant: 435 (39.9%) received grafts from donors after circulatory death (DCD), 366 (33.6%) from donors after brain death (DBD) and 289 (26.5%) from living donors. Early graft loss occurred in 52 (4.8%) recipients. Causes included acute vascular occlusion (19; 1.7%), primary non-function (19; 1.7%), haemorrhage (7; 0.6%) and rejection (3; 0.3%). Only DCD donor type was a significant risk factor for early graft loss (p=0.006), although one-year graft survival after DCD and DBD transplantation was similar (89.9% vs 93.2%; p=0.089). Patients with early graft loss had 8.5 times increased risk of death (p<0.001; figure 1); their one-year patient survival was less than those on the waiting list (76.9% vs 88.8%), but 5-year patient survival in the early graft loss group was better (69.3% vs 51.4%; log-rank test: p=0.030). Re-transplantation after early graft loss was associated with a good outcome with a one-year graft survival of 86.7%. Our findings suggest that DCD donation is a significant risk factor for early graft loss. Early kidney graft loss, irrespective of donor type, is a major risk factor for patient mortality. However, long-term patient survival after early kidney graft loss is still superior to the survival of those who remain on the waiting list. Kidney re-transplantation was associated with a high success rate and should be considered.Figure: No Caption available.

Pre-activated blood platelets and a pro-thrombotic phenotype in APP23 mice modeling Alzheimer's disease

Platelet activation and thrombus formation play a critical role in primary hemostasis but also represent a pathophysiological mechanism leading to acute thrombotic vascular occlusions. Besides, platelets modulate cellular processes including inflammation, angiogenesis and neurodegeneration. On the other hand, platelet activation and thrombus formation are altered in different diseases leading to either bleeding complications or pathological thrombus formation. For many years platelets have been considered to play a role in neuroinflammatory diseases such as Alzheimer's disease (AD). AD is characterized by deposits of amyloid-β (Aβ) and strongly related to vascular diseases with platelets playing a critical role in the progression of AD because exposure of platelets to Aβ induces platelet activation, platelet Aβ release, and enhanced platelet adhesion to collagen in vitro and at the injured carotid artery in vivo. However, the molecular mechanisms and the relation between vascular pathology and amyloid-β plaque formation in the pathogenesis of AD are not fully understood. Compelling evidence is suggestive for altered platelet activity in AD patients. Thus we analyzed platelet activation and thrombus formation in aged AD transgenic mice (APP23) known to develop amyloid-β deposits in the brain parenchyma and cerebral vessels. As a result, platelets are in a pre-activated state in blood of APP23 mice and showed strongly enhanced integrin activation, degranulation and spreading kinetics on fibrinogen surfaces upon stimulation. This enhanced platelet signaling translated into almost unlimited thrombus formation on collagen under flow conditions in vitro and accelerated vessel occlusion in vivo suggesting that these mice are at high risk of arterial thrombosis leading to cerebrovascular and unexpectedly to cardiovascular complications that might be also relevant in AD patients.

Cocaine in high concentrations inhibits platelet aggregation in vitro

Complications of cocaine administration are acute vascular occlusions such as myocardial infarction and stroke. We have studied the influence of cocaine on platelet function in vitro. For that purpose, citrated blood from healthy volunteers was incubated with cocaine concentrations of 0 (control), 10, 100, 1000, 2500, and 10'000 μmol/l plasma. Platelet aggregation was measured in whole blood under high shear flow conditions with a platelet function analyzer PFA-100 using either epinephrine (EPI) or ADP as a platelet activator, as well as in non-flowing blood measuring the change of impedance after the addition of either collagen or ADP (Chronolog-700 Aggregometer). In addition, platelet aggregation was measured by the change in light transmission in platelet rich plasma containing the same cocaine concentrations (Chronolog-700). Platelet aggregation in flowing whole blood (PFA-100) was not affected by cocaine up to 1000 μmol/l, partially inhibited by 2500 μmol/l and completely inhibited by 10'000 μmol/l cocaine. In non-flowing blood, platelet aggregation was decreased already at cocaine concentrations of 1000 μmol/l with ADP and 2500 μmol/l with collagen as a platelet activator. In platelet-rich plasma, aggregation was partially inhibited by 1000 and 2500 μmol/l and completely inhibited by 10'000 μmol/l cocaine. We conclude that platelet aggregation is inhibited by cocaine in vitro. This occurs, however, at concentrations above those measurable in vivo. These observations make it very unlikely that a direct platelet activation plays a role in vascular events complicating cocaine consumption.