Cerebral Vascular Complications Research Articles

Disastrous cerebral and ocular vascular complications after cosmetic facial filler injections: a retrospective case series study

Soft tissue filler injections are among the most popular facial rejuvenation methods. Cerebral infarction and ophthalmic artery occlusion are rare and catastrophic complications, especially when facial cosmetic fillers are injected by inexperienced doctors. Radiologists and plastic surgeons need to increase their awareness of the complications associated with fillers, which allows early diagnosis and intervention to improve patient prognosis. Regarding the mechanism by which vascular occlusion occurs after facial filler injections, a retrograde embolic mechanism is currently the predominant theory. Numerous case reports have been presented regarding complications associated with injections of facial aesthetics. However, the small sample sizes of these studies did not allow for an adequate assessment of the clinical and imaging manifestations based on the location of the occlusion and the type of filler, and detailed elaboration of multiple cerebral infarctions is also lacking. Therefore, this study aimed to investigate the clinical and radiological features of severe cerebral and ocular complications caused by cosmetic facial filler injections. In addition, we discuss the pathogenesis, treatment, and prognosis of these patients. The clinical, computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) findings were described and analysed. Radiological examinations are crucial for demonstrating severe complications, and brain MRI is especially strongly suggested for patients with cosmetic filler-induced vision loss to identify asymptomatic cerebral infarctions. Extreme caution and care should be taken during facial injections by plastic surgeons.

Alternative (Transulnar or Distal Radial) Arterial Access for Chronic Total Occlusion Percutaneous Coronary Intervention (Subanalysis from the Minimalistic Hybrid Approach Algorithm Registry)

The transradial approach (TRA) has become the primary choice for percutaneous coronary intervention (PCI); however, it may not be always feasible because of clinical and/or technical challenges. Alternative forearm accesses, such as transulnar approach (TUA) and distal radial approach (dTRA) may allow maintaining a wrist approach for the procedure, avoiding the femoral artery. This issue is particularly relevant in patients who underwent multiple revascularizations, such as those with chronic total occlusion (CTO) lesions. This study aimed to evaluate whether the use of TUA and/or dTRA is comparable with TRA in CTO PCI using a minimalistic hybrid approach algorithm, which limits the number of accesses used to minimize vascular access complications. Patients with CTO PCI treated solely through a fully alternative approach (TUA and/or dTRA) were compared with those treated solely through a standard TRA approach. The primary efficacy end point was procedural success, whereas the primary safety end point was the composite of major adverse cardiac and cerebral events and vascular complications. Of 201 CTO PCIs attempted, 154 procedures were considered for analysis (standard, n = 104, alternative, n = 50). Alternative and standard groups demonstrated comparable rates of both procedural success (92% vs 94.2%, p = 0.70) and primary safety end point (4.8% vs 6.0%, p = 0.70). Of interest, 7 French guiding catheters were more frequently used in the alternative group (44% vs 26%, p = 0.028). In conclusion, CTO PCI after minimalistic hybrid approach by way of alternative forearm vascular accesses (dTRA and/or TUA) is feasible and safe to perform, compared with CTO PCI by way of standard TRA.

The psychoactive drug of abuse mephedrone differentially disrupts blood-brain barrier properties

BackgroundSynthetic cathinones are a category of psychostimulants belonging to the growing number of designer drugs also known as “Novel Psychoactive Substances” (NPS). In recent years, NPS have gained popularity in the recreational drug market due to their amphetamine-like stimulant effects, low cost, ease of availability, and lack of detection by conventional toxicology screening. All these factors have led to an increase in NPS substance abuse among the young adults, followed by spike of overdose-related fatalities and adverse effects, severe neurotoxicity, and cerebral vascular complications. Much remains unknown about how synthetic cathinones negatively affect the CNS and the status of the blood-brain barrier (BBB).MethodsWe used in vitro models of the BBB and primary human brain microvascular endothelial cells (hBMVEC) to investigate the effects of the synthetic cathinone, 4-methyl methcathinone (mephedrone), on BBB properties.ResultsWe showed that mephedrone exposure resulted in the loss of barrier properties and endothelial dysfunction of primary hBMVEC. Increased permeability and decreased transendothelial electrical resistance of the endothelial barrier were attributed to changes in key proteins involved in the tight junction formation. Elevated expression of matrix metalloproteinases, angiogenic growth factors, and inflammatory cytokines can be explained by TLR-4-dependent activation of NF-κB signaling.ConclusionsIn this first characterization of the effects of a synthetic cathinone on human brain endothelial cells, it appears clear that mephedrone-induced damage of the BBB is not limited by the disruption of the barrier properties but also include endothelial activation and inflammation. This may especially be important in comorbid situations of mephedrone abuse and HIV-1 infections. In this context, mephedrone could negatively affect HIV-1 neuroinvasion and NeuroAIDS progression.

Brain Computed Tomography in Stimulant Poisoning with Altered Consciousness.

Stimulant poisoning frequently causes altered mental status (AMS) and can result in severe cerebral vascular complications. The role of noncontrast brain computed tomography (CT) in acute stimulant-poisoned patients presenting with AMS remains unclear. We examined the results and impacts of brain CT in acute stimulant-poisoned patients with AMS. We performed a retrospective single-center study that included all adult patients who presented to the emergency department with stimulant poisoning and AMS (Glasgow coma scale [GCS] score <15) between January 1, 2010 and December 31, 2017. Patients who had concomitant head trauma or who presented with focal neurologic symptoms were excluded. The primary outcome was the rate of acute abnormalities on brain CT. The secondary outcomes were to identify factors that affected the decision to perform brain CT in stimulant-poisoned patients with AMS and whether obtaining the brain CT scan itself affected the patients' prognoses. The analysis included 66 patients, of whom 6 died from the poisoning. Noncontrast brain CT was performed in 31 patients and none had acute abnormalities. Patients who underwent brain CT were found to have worse GCS scores, higher body temperatures, higher intubation rates, higher admission rates, longer admission periods and intensive care unit stays, and a higher mortality rate. After adjusting for the propensity score, performing brain CT itself did not independently affect the patients' clinical outcomes. Nontrauma stimulant-poisoned patients presenting with AMS and without focal neurologic symptoms were unlikely to have acute abnormalities on brain CT. Patients who underwent brain CT scans had worse consciousness and greater disease severity.

Intracerebral Hemorrhage in Women: A Review with Special Attention to Pregnancy and the Post-Partum Period

Non-traumatic intracranial hemorrhage includes subarachnoid hemorrhage, subdural hemorrhage, and intracerebral hemorrhage (ICH), which can be classified as primary or secondary. Primary ICH is due to arterial hypertension or cerebral amyloid angiopathy, and secondary ICH is due to cerebral vascular malformations, coagulopathies, infectious complications, brain tumors, and illicit stimulant drug use. This review explores the epidemiology and management of non-traumatic ICH in women, with a focus on pregnancy and the post-partum period, defined as 6weeks post-delivery.

Terminal end Variations and Common Pathological Abnormalities of the Basilar Artery among the Ugandan Population: a Human Autopsy Study

Introduction Morphological variations at the basilar artery terminal end are documented risk factors for cerebral vascular complications like atherosclerosis, thromboembolisms, and aneurysms that further predispose to fatal arterial occlusions. Pathological abnormalities of the basilar artery are usually ignored on diagnosis in third world countries despite their role in brain ischemia. There is a paucity of literature on the gross anatomy of cerebral vasculature in the Ugandan population. Therefore, this study set out to determine the terminal end variations and common pathological abnormalities of the basilar artery among the Ugandan population. Materials and Methods This was a cross sectional study that accessed intact basilar arteries from 115 human autopsy brains (77 males and 33 females) at the Kampala City Council Authority mortuary. Arachnoid matter was removed and arteries perfused with clear water for visibility. The arteries were checked for variations including bifurcations, trifurcations, quadrifurcation, hexafuraction and pathological abnormalities. Representative photographs were taken and results presented as proportions and percentages. Results The average age of the human cadavers was 38 years (Range 18–85 years). Normal bifurcation of the basilar artery was observed in 48.7% of the study population. Other variations included trifurcations (22.6%); quadrifurcations (21.7%), pentafurcations (6.1%) and hexafurcations (0.6%). With regard to abnormalities, 16 arteries (13.9%) had atheromatous plaques, 21 (18.3%) were rigid, and 26 (22.6%) were tortuous. There was significant correlation between age and pathological abnormalities (p = 0.01) Conclusion There are several variations at the terminal end of the basilar artery in the Ugandan population. Arterial pathological abnormalities are also not uncommon and tend to increase with age. Thus, the need for routine imaging investigations in patients with cerebrovascular disorders and individuals of 40 years and above.

Evaluation of late cerebral vascular complications in cranially irradiated pediatric cancer patients with magnetic resonance angiography.

We aimed to establish the early diagnosis of cerebral vascular complications by using cerebral magnetic resonance angiography (MRA) in patients who were treated with cranial RT in childhood as part of their cancer treatment. Patients who had received cranial RT before the age of 18 and had been in remission for at least 1 year were enrolled in the study. A data form including demographic and clinical characteristics and findings of cerebral MRA was filled in for each patient. Cerebral MRA examination was performed between November 2013 and October 2015 in 53 patients who met the inclusion criteria. Abnormalities were found in 7 patients (13.2%). All patients were asymptomatic at the time of examination. There was a significant difference between patients in the abnormality-positive and abnormality-negative groups related to cranial radiation dose (p = 0.013) and age at the time of examination (p = 0.015) in univariate analysis. In multivariate analysis, cranial radiation dose was found to have an impact on developing cerebral vascular abnormalities (p = 0.045). Cerebral MRA is a noninvasive method of follow-up for late cerebral vascular complications in surviving pediatric oncology patients who were treated with cranial RT as part of their cancer treatment.

Вариабельность артериального давления в разные дни: методологические аспекты оценки, прогностическая значимость, влияние антигипертензивной терапии

In this article we present problems of prognostic value of day-by-day blood pressure (BP) variability, its role in development and progression of damage of target organs in arterial hypertension, and impact on risk of cardiovascular, cerebral-vascular complications, and mortality. We also discuss methodological aspects of assessment of day-by-day BP variability. The article contains literature data on effects of antihypertensive therapy on variability of home BP, and consideration of evidence base of possibilities of the fixed amlodipine/perindopril combination for lowering day-by-day BP variability.

The complex evaluation of lipid metabolism and blood coagulation system indicators for prediction and early diagnosis of the preeclampsia

Aim. To study informative and prognostic significance of lipid metabolism markers and coagulation system condition for PE early diagnostics in pregnant women during the second gestational trimester with risk evaluation of cardiovascular and metabolic pathologies in the given women category.Materials and methods. The analysis of blood serum samples in 267 pregnant women in II gestational trimester was carried out. The total cholesterol was determined by colorimetric method, enzymatic with CHOD/PAP, TG – by enzymatic colorimetric method, HDL – by homogeneous method, LDL – by direct method. VLDL concentration was calculated according to Fridvald's formula: VLDL = TG/2.2. AF was calculated according to the formula: AF = (TC-HDL-c)/HDL-c. Pregnant women in II and III gestational trimesters also were examined concerning the general assessment of coagulation system condition – the concentration in blood plasma of D-dimer, soluble fibrin (SFMC), fibrinogen, FIPF, protein C activity, AT III, blood plasma clotting time was determined by PT test.Results. Of the 267 pregnant women, in 43 (16.1 %) of them, which formed the main group for research, the development of PE was found. Those pregnant women, who had PE clinical picture of the different severity levels, from the second trimester had significantly elevated TG, VLDL, AF levels, and low level of HDL in blood serum with high concentration of D-dimer (from 80 to 713 ng/ml), as well as protein C low activity in 17.6 % of pregnant women. In the third trimester pregnant women, having PE, fibrinogen content was significantly higher (4.4±1.02); the accumulation of a significant amount of SF, accompanied by FIPF presence in 40 % of pregnant women, was found in 50 % of pregnant women; a significant reducing (˂70 %) of the protein C activity was found in 48 % of patients.Conclusion. Both significant increasing of the soluble fibrin in blood plasma, and reducing of the protein C activity below 70 % are thrombosis prognostic indexes. The control of lipid metabolism and coagulation system indexes is necessary during all stages of pregnancy for estimation of PE risk and cardiovascular,cerebral vascular and metabolic complications prevention

Angiotensin II Receptor Blockers or Straight Renin Inhibitor Influence Upon Morphological and Functional Heart and Central Hemodynamics Indices in Hypertensive Patients After Ischemic Stroke

Arterial hypertension (AH) in the world and in Ukraine is the main cause of strokes and chronic cerebral dyscirculation with constantly growing incidence. The risk of recurrent stroke grows with increase of concomitant risk factors and AH target organs damage. Asymptomatic target organs damage, especially, LV hypertrophy, etc., is one the potent factors for cerebral vascular complications in hypertensive patients. That is why treatment of heart anatomy alterations, as a target organ, is of great importance in cardiovascular continuum for primary and secondary prevention of cardiovascular, including cerebrovascular end-points. The objective: of the study was to evaluate the influence of AH medication treatment by angiotensin receptors type II blockers (ARB) and straight renin inhibitor upon morphological and functional heart indices and central hemodynamics in hypertensive patients after ischemic stroke (IS) during 1 year follow-up according to stroke and vascular hospital departments experience. Patients and methods. We prospectively included 135 hypertensive pts. without AF history after IS aged 36-78 years (61,0±9,1 yrs.), hospitalized to stroke and vascular hospital departments of Ternopol regional community psycho-neurological hospital (TRCPNH) over the period Nov. 2011 – Dec. 2013 р. All pts. underwent Doppler EchoCG. Along with fundamental therapy pts. were randomly prescribed Losartan 50-100 mg/day (40 pts.), Olmesartan 20-40 mg/day (48 pts) or Aliskiren 150-300 mg/day. Control EchoCG was performed in 6 and 12 months from trearment start. Results. Among the pts. with AH after IS usually there are pts. with low NYHA class of CHF, with LVEF correlating with NYHA functional class ( –0,47, p&lt;0,0001), with predominantly concentric LV geometry (97,8%), correlating with NYHA functional class. NYHA FC significantly correlates with most morphological and functional left and right remodeling indices, while LV volumes significantly correlate with LV systolic function. ARB administration (Losartan or Olmesartan) for AH treatment leads to marked significant regress of LV hypertrophy and hypertensive remodeling already in 6 months of treatment with central hemodynamics improvement with similar changes in both sartans groups without significant difference between indices. In Aliskiren group (3) in 6 months of treatment pts. Showed significantly higher LA dimensions compared to Losartan group, thicker LV walls compared to both sartan groups, and higher LV RWTh. Central hemodynamics indices, namely, LV diastolic function, LV preload and smaller circulation pressure in 6 months after treatment did not significantly differ between the groups. Conclusions. In Aliskiren group in 12 months of treatment there also were certain positive changes compared to start data, witnessing of reverse LV remodeling. But at the same time Aliskiren group showe significantly higher LV walls thickness (р=0,0051 and р&lt;0,0001 for IVS, and р&lt;0,0001 and р&lt;0,0001 fro LVPW, respectively), and higher LV MMi (р=0,0003 and р=0,0002, respectively) compared both to Losartan and Olmesartan groups, with preservation of concentric LV geometry and LV hypertrophy. Also, Aliskiren group showed significantly worse LV diastolic function and preload indices, allowing to conclude about insufficient cardioprotection with Aliskiren in treating AH after IS, and significant benefit from ARB.

Role of Hypoxia Inducible Factor 1 in Hyperglycemia-Exacerbated Blood-Brain Barrier Disruption in Ischemic Stroke

Diabetes is a major stroke risk factor and is associated with poor functional recovery after stroke. Accumulating evidence indicates that the worsened outcomes may be due to hyperglycemia-induced cerebral vascular complications, especially disruption of the blood-brain barrier (BBB). The present study tested a hypothesis that the activation of hypoxia inducible factor-1 (HIF-1) was involved in hyperglycemia-aggravated BBB disruption in an ischemic stroke model. Non-diabetic control and Streptozotocin-induced type I diabetic mice were subjected to 90min transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Our results demonstrated that hyperglycemia induced higher expression of HIF-1α and vascular endothelial growth factor (VEGF) in brain microvessels after MCAO/reperfusion. Diabetic mice showed exacerbated BBB damage and tight junction disruption, increased infarct volume as well as worsened neurological deficits. Furthermore, suppressing HIF-1 activity by specific knock-out endothelial HIF-1α ameliorated BBB leakage and brain infarction in diabetic animals. Moreover, glycemic control by insulin abolished HIF-1α up-regulation in diabetic animals and reduced BBB permeability and brain infarction. These findings strongly indicate that HIF-1 plays an important role in hyperglycemia-induced exacerbation of BBB disruption in ischemic stroke. Endothelial HIF-1 inhibition warrants further investigation as a therapeutic target for the treatment of stroke patients with diabetes.

DPP-4 inhibition with linagliptin ameliorates cognitive impairment and brain atrophy induced by transient cerebral ischemia in type 2 diabetic mice.

BackgroundIt is unclear whether dipeptidylpeptidase-4 (DPP-4) inhibition can counteract the impairment of cognitive function and brain injury caused by transient cerebral ischemia in type 2 diabetes. The present study was undertaken to test our hypothesis that linagliptin, a DPP-4 inhibitor, administration following transient cerebral ischemia can ameliorate cognitive impairment and brain injury in diabetic mice.Methodsdb/db mice, a model of obese type 2 diabetes, were subjected to transient cerebral ischemia by 17 min of bilateral common carotid artery occlusion (BCCAO), and were administered (1) vehicle or (2) linagliptin for 8 weeks or 1 week. For the long-term experiment on 8 weeks of linagliptin treatment, cognitive function, and volume and neuronal cell number of hippocampus and cortex were estimated in each group of mice. For the short-term experiment on 1 week of linagliptin treatment, cerebral IgG extravasation, Iba-1 positive cell number (reactive microglia), oxidative stress, and claudin-5 and gp91phox protein levels were measured in each group of mice.ResultsLinagliptin administration almost completely suppressed the circulating DPP-4 activity in db/db mice, but did not significantly reduce blood glucose or ameliorate glucose intolerance in db/db mice. Linagliptin administration following transient cerebral ischemia significantly counteracted cognitive impairment in diabetic mice, as estimated by water maze test and passive avoidance test. Linagliptin administration ameliorated the decrease in cerebral volume and neuronal cell number in hippocampus and cortex of diabetic mice. Linagliptin administration significantly reduced the increase in cerebral IgG extravasation and the increase in reactive microglia caused by transient cerebral ischemia in diabetic mice. Furthermore, linagliptin significantly suppressed the increase in cerebral oxidative stress in transient cerebral ischemia-subjected diabetic mice. Furthermore, linagliptin significantly increased cerebral claudin-5 and significantly decreased gp91phox in diabetic mice subjected to transient cerebral ischemia.ConclusionsDPP-4 inhibition with linagliptin counteracted cognitive impairment and brain atrophy induced by transient cerebral ischemia in diabetic mice, independently of blood glucose lowering effect. This cerebroprotective effect of linagliptin was associated with the suppression of blood-brain barrier disruption and the attenuation of cerebral oxidative stress. Thus, our present work highlights DPP-4 inhibition as a promising therapeutic strategy for cognitive impairment and cerebral vascular complications in type 2 diabetes.

Pathogenesis of diabetic cerebral vascular disease complication.

Diabetes mellitus is one of the most potent independent risk factors for the development of diabetic cerebral vascular disease (CVD). Many evidences suggested that hyperglycemia caused excess free fatty acids, the loss of endothelium-derived nitric oxide, insulin resistance, the prothrombotic state, endothelial dysfunction, the abnormal release of endothelial vasoactivators, vascular smooth muscle dysfunction, oxidative stress, and the downregulation of miRs participated in vessel generation and recovery as well as the balance of endotheliocytes. In turn, these abnormalities, mainly via phosphatidylinositol 3 kinase, mitogen-activated protein kinase, polyol, hexosamine, protein kinase C activation, and increased generation of advanced glycosylation end products pathway, play an important role in inducing diabetic CVD complication. A deeper comprehension of pathogenesis producing diabetic CVD could offer base for developing new therapeutic ways preventing diabetic CVD complications, therefore, in the paper we mainly reviewed present information about the possible pathogenesis of diabetic CVD complication.

Before the Jury Is out on Cinacalcet’s Cardiovascular Effects in Hemodialysis Patients: Is Troponin a Missing Link?

Raised levels of the cardiac biomarker, Troponin I, are frequently encountered in hemodialysis patients and appear to be prognostic indicators for cardiovascular risk. Though evidence suggests that control of secondary hyperparathyroidism may reduce cardiac endpoints, the effect of the calcimimetic agent, cinacalcet, remains controversial. This retrospective study aimed at evaluating troponin levels in hemodialysis patients with severe secondary hyper parathyroidism (SHPT) who are on cinacalcet vs controls on conventional treatment. In addition, clinical outcomes including all-cause, cardiovascular morbidity and mortality were compared among both groups. A decline in Troponin I levels was observed in the cinacalcet group, this however was not translated clinically into improved survival. In fact, all-cause and cardiac mortality was similar in the two groups. Conversely, comparison of the incidence of cardiovascular events revealed lower rates in the cinacalcet group including cardiac, cerebral and peripheral vascular complications. Given some of our study limitations, further long-term, placebo-controlled trials are necessary to definitively establish the effect of cinacalet on cardiac biomarkers and ultimately its impact on clinical outcomes.

Glutathione Prevents Free Fatty Acids‐Induced Oxidative Stress and Apoptosis in Human Brain Vascular Endothelial Cells Through Akt Pathway

The damage of human brain vascular endothelial cells (HBVECs) is the key pathogenesis of diabetes-associated cerebral vascular complications. The aim of this study was to elucidate the effects of glutathione (GSH) on free fatty acids (FFAs)-induced HBVECs apoptosis, oxidative stress, and the involved possible signaling pathway. After culturing HBVECs for 72 h with GSH and FFAs, we determined cell proliferation by CCK8, detected apoptosis by caspase-3 and Annexin V-FITC/PI staining, and judged oxygen stress by determining the reactive oxygen species (ROS) and the mitochondrial membrane potential (MMP). We investigated whether the Akt pathway was involved in FFAs-induced signaling pathway alteration and whether GSH influenced the above effects. After being cultured in 200 μM FFAs for 72 h, the HBVECs proliferation significantly decreased; HBVECs apoptosis increased; the ROS levels increased; and the HBVECs MMP subsequently decreased. FFAs induced a significant decrease in phosphorylated active Akt. These alterations were obviously prevented when 1 mM GSH was added to culture medium containing FFAs, and the above effects of GSH were blocked by Akt inhibitor. GSH may prevent FFAs-induced HBVECs damage, oxidative stress, and apoptosis through activating the Akt pathway.

Aortenklappenstenosen

The calcified aortic stenosis is the dominating valve disease. Patients affected are most common elderly people in the 8 (th) or 9 (th) decade of their life who often show associated comorbidities like reduced left ventricular function, impaired renal function, pulmonary hypertension, and further diseases (Diabetes mellitus, stroke, COPD). In many cases perioperative morbidity and mortality are too high for surgical valve replacement and up to 30 % of patients are rejected. Nevertheless, prognosis of aortic stenosis is worse if the typical symptoms like dyspnea on exertion, syncope, and angina occur. The transcatheter aortic valve implantation is a new method treating this particular group of patients. The aortic valve bioprothesis consists of a balloon-expandable stent or a self-expandable frame, in which a valve of bovine or porcine pericardium is incorporated. The implantation is performed by retrograde access via the femoral or subclavian artery; the balloon-expandable prosthesis can also be implanted by transapical approach. Recently, the PARTNER trial and other studies demonstrate a high implantation success rate and better survival in comparison to standard therapy but exhibit also cerebral vascular and peripheral vascular complications. A further reduction of the available delivery systems and new types of valves which are under experimental tests and clinical evaluation contribute to this development.

Change of serum C-type natriuretic peptide level in patients with essential hypertension

Objective To explore the change of serum level of C-type natriuretic peptide in patients with essential hypertension and to evaluate the relationship between the serum level of C-type natriuretic peptide and stage of hypertension as well as target organ injury. Methods The serum level of C-type natriuretic peptide were determined with radioimmunossay in 97 EH patients and 50 controls. Results The serum levels of C-type natriuretic peptide in EH patients were significantly higher than those in controls. The serum levels of C-type natriuretic peptide increased gradually from grade 1 to grade 3 EH. The serum levels of C-type natriuretic peptide in patients with renal and/or cardio and/or cerebral vascular complications were significantly higher than those in patients without complications. The differences were significant, P ＜ 0. 05. Conclusion The serum level of C-type natriuretic peptide in EH patients were closely related to the severity of EH process and target organ injuries. Key words: Essential hypertension; C-type natriuretic peptide; Radioimmunossay

Experimental Diabetes Mellitus Down-Regulates Large-Conductance Ca2+- Activated K+ Channels in Cerebral Artery Smooth Muscle and Alters Functional Conductance

Cerebral vascular dysfunction and associated vascular complications often develop over time in type-2 diabetes, but the underlying mechanisms are not wholly understood. The aim of the present study was to investigate whether large-conductance Ca(2+)-activated K(+) (BKCa) channels in cerebral artery smooth muscle cells (CASMCs) were impaired in experimental model of type-2 diabetes, and the changes could account for cerebral vascular complication in type-2 diabetes. Sprague-Dawley rats were fed with high fat and glucose diet for 8 weeks and then injected with streptozotocin (STZ/30 mg/kg i.p.). Three months after injection of STZ, the alterations of BKCa channels were assessed by using multi-myograph system, patch-clamp, RT-PCR and Western blot. Our results show that the model is characterized by insulin resistance, hyperglycaemia, hyperlipidemia and moderate hypertension, which resembles the clinical manifestation of patients with typre-2 diabetes. Inhibition of BKCa channels with 1 mM tetraethylammonium (TEA) or 1 microM paxilline (PAX) causes smaller constriction in type-2 diabetic cerebral basilar arteries than control arteries. The contractile efficacy of 5-Hydroxytryptamine (5-HT) is substantially reduced by TEA or PAX pretreatment in control > diabetic basilar artery rings. The response to 5-HT in diabetic basilar artery rings is higher than that of control artery rings after activation of BKCa channels with NS1619. The whole-cell K(+) currents are significantly decreased in type-2 diabetic CASMCs compared to control, and the sensitivity of BKCa channels to voltage, the specific inhibitor and opener are all diminished in diabetic CASMCs. The expression of BKCa channel beta1, but not alpha-subunits is markedly reduced at both of mRNA and protein levels in endothelial-denudated cerebral arteries. In conclusion, type-2 diabetes downregulates BKCa channel beta1-subunits in CASMCs, resulting in reduced activity of BKCa channel, increased vascular tone and blood pressure, thereby contributing to cerebral vascular complication in type-2 diabetes.

Antiagregantes y anticoagulantes: manejo del paciente quirúrgico anticoagulado

Among the drugs most widely consumed by patients are both antiplatelet agents (aspirin, clopidogrel, ticlopidine) and anticoagulants (acenocoumarol, warfarin, low molecular weight heparin, fondaparinux). The use of these drugs in the perioperative period is an essential concern in patient care due to the need to balance the risk of bleeding against thrombotic risk (arterial or venous), which is increased in surgical patients. The present review highlights three main aspects. Firstly, withdrawal of antiplatelet agents is recommended between 1 week and 10 days before surgery to minimize perioperative bleeding. However, this practice has been questioned because patients without the required antiplatelet coverage may be at greater risk of developing cardiac, cerebral or peripheral vascular complications. Therefore, the recommendation of systematic antiplatelet withdrawal for a specific period should be rejected. Currently, risks should be evaluated on an individual basis to minimize the time during which the patient remains without adequate antiplatelet protection. Secondly, thromboprophylaxis is required in most surgical patients due to the high prevalence of venous thromboembolic disease. This implies the use of anticoagulants and the practice of regional anesthesia has been questioned in these patients. However, with the safety recommendations established by the various scientific societies, this practice has been demonstrated to be safe. Finally, «bridge therapy» in patients anticoagulated with acenocoumarol should be performed on an individual basis rather than systematically without taking into account the thrombotic risks of each patient. The perioperative period involves high arterial and venous thrombotic risk and the optimal use of antiplatelet agents and anticoagulants should be a priority to minimize this risk without increasing hemorrhagic risk. Multidisciplinary consensus is essential on this matter.

Allogeneic stem cell transplantation improves cerebro-vascular disease in two sickle cell anemia patients

16524 Background: Sickle cell anemia (SCA) patients are at high risk for vaso-occlusion with cerebral vascular complications like strokes being one of the most devastating clinical events. Prophylactic transfusions might prevent strokes resp. improve cerebro-vascular status in SCA patients. Allogeneic stem cell transplantation (SCT) is considered a therapeutic option with curative intention of SCA, and thus also to improve cerebro-vascular complications by preventing further strokes, as demonstrated by two cases in our center. Methods: Transcranial Doppler sonography (TCD) and cerebral magnetic resonance angiography (MRA) were used to assess cerebro-vascular disease status prior, during and post related SCT of 2 SCA patients. Results: Two sibling SCA patients (male resp. female, aged 13 and 11 years resp.) both suffered from multiple cerebral microinfarcts during the course of their disease, the boy additionally suffered from two strokes. Prior to related SCT in 2004 with unaffected siblings, both patients were assessed by MRA and TCD. The diagnostic data revealed a hypoplastic ACI (right side) in both children as prominent pathological feature, in combination with different grades of stenosises of ACM, AV and ACI (left side), for example. The evaluation of cerebro-vascular status 3–4 months post SCT showed a persisting stenosis of right ACI in both patients, whereas circulation in the cerebrum resp. flow velocity profiles in other intracranial arteries significantly improved or turned to normal. The course of SCT was rather uncomplicated in the immediate post-transplant period except clinically controlled acute GvHD grade III in one patient. Currently, i.e. 18 resp. 21 months after transplant, the children are in good clinical condition. Conclusions: The results of allogeneic SCT in 2 SCA patients suggest that cerebro-vascular disease does not progress after SCT resp. shows major improvement by SCT. Regular follow up is necessary to assess long term results of cerebro-vascular status in these patients. No significant financial relationships to disclose.