[Influence of ECMO and IABP on coronary blood flow. Valuable combination or waste of resources?]. / Einfluss von ECMO und IABP auf die Koronardurchblutung. Sinnvolle Kombination oder Ressourcenverschwendung?

BACKGROUND: The treatment of patients in severe cardiogenic shock with an intra-aortic balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO) is a common procedure to achieve stabilization. Only limited data are available on the simultaneous use of both systems. The aim of the present study was to assess the effect of the concomitant use of IABP and ECMO on coronary blood flow. In addition, the influence of antegrade and retrograde perfusion was evaluated. METHODS: A median sternotomy was performed in adult pigs under general anesthesia. Arterial ECMO perfusion was realized through the ascending aorta or the femoral artery, and the IABP was implanted via the second femoral artery. Six measurements of arterial pressure in the left anterior descending artery (LAD) and in the left atrium were made at intervals of 2 min. In addition, lactate concentration and oxygen saturation in the coronary sinus were recorded. The ECMO support was either 100 or 50 % of cardiac output. Each experiment was carried out first without and then with additional IABP support. RESULTS: The simultaneous use of ECMO and IABP is feasible for antegrade perfusion, where the IABP leads to an increase of blood pressure in the coronary arteries. In addition, the myocardial oxygen supply improves. By contrast, the use of an IABP in retrograde perfusion leads to a reduction of blood pressure in the LAD and to a reduced oxygen supply. A comparison between antegrade and retrograde perfusion with IABP support showed significantly better mean arterial pressure in the LAD for antegrade perfusion. Without IABP, blood pressure in the LAD was better in retrograde perfusion. CONCLUSION: In antegrade perfusion the simultaneous use of IABP and ECMO is useful. In retrograde perfusion IABP impairs the mean arterial pressure and consequently the perfusion of the coronary arteries.

[Aneurysms of the ascending aorta and aortic arch]. / Aneurysmen der Aorta ascendens und des Aortenbogens.

BACKGROUND: The treatment of patients with aneurysms of the ascending aorta and aortic arch often represents a challenge due to their complexity. The clinical picture is characterized by further progression of the disease and severe complications, such as acute aortic dissection or even aortic rupture are not uncommon. OBJECTIVES: This article gives a review of definitions, etiology and indications for operative treatment of patients with aneurysms of the ascending aorta and aortic arch. RESULTS AND DISCUSSION: An aortic aneurysm of the ascending aorta is defined as a dilatation of all wall layers of the aorta of more than 50 % in comparison to the normal diameter. This is dependent on age, sex, body surface area and the underlying diseases. In most cases the cause is the presence of atherosclerosis. Connective tissue diseases, bicuspid or monocuspid aortic valves and aortitis represent additional risk factors. Surgical treatment of the ascending aorta, aortic root and aortic arch is carried out in patients without connective tissue diseases and a diameter of ≥ 55 mm and for patients with Marfan syndrome and bicuspid aortic valves with a diameter of ≥ 50 mm. Earlier indications for surgery are present with an aortic diameter of ≥ 45 mm in patients with the following risk factors: familial disposition for aortic dissection (often unrecognized as sudden cardiac death), annual growth rate of the aortic diameter of > 2 mm, comorbid severe aortic valve or mitral valve insufficiency and female patients with a desire to have children. The standard surgical procedures include aortic root replacement, aortic valve reconstruction with aortic root or ascending aorta replacement and partial or total aortic arch replacement depending on the extent of the aneurysm. The so-called hybrid procedures for aortic arch surgery include frozen elephant trunk (ET) techniques and debranching procedures. Good perioperative and postoperative results can be achieved by early diagnostics and an assessment of the indications depending on the individual etiology. Individual and valve-preserving treatment strategies have a favorable influence on the operative outcome.

Spinal cord ischemia in open and endovascular thoracoabdominal aortic aneurysm repair: new concepts.

For more than half a century ischemic spinal cord injury (SCI) and consecutively permanent paraplegia remained the most devastating complication after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Various neuroprotective strategies (e.g., motor-/somatosensory evoked potential monitoring and cerebrospinal fluid drainage) used as adjuncts have lowered the SCI; maybe most importantly, the modern collateral network (CN) has begun to replace the classic understanding of spinal cord blood supply implying several consequences. Reliable non-invasive tools to monitor cord perfusion to detect imminent spinal cord malperfusion, ischemia and forthcoming neurologic injury (particularly early postoperatively) is not available, neither is a reliable strategy to prevent ischemic injury during distal circulatory arrest and after segmental artery occlusion. Currently, two promising new concepts--potentially advancing spinal protection in open and endovascular TAAA repair--address these issues: 1) non-invasive real-time monitoring of the paraspinous CN-oxygenation via near-infrared spectroscopy (NIRS) as an alternative to the demanding direct neuromonitoring; and 2) preconditioning of the CN as minimally invasive, endovascular "first stage" to increase the resilience of spinal cord perfusion prior to definite aortic repair. This article illustrates both concepts discussing: 1) the clinical application of thoracic and lumbar collateral NIRS monitoring to indirectly detect spinal cord hypoperfusion; and 2) minimally invasive selective segmental artery coil-embolization (MISACE) for (arteriogenic) preconditioning of the CN prior to extensive open or endovascular staged TAAA repair.

Dislocation of a transapically implanted aortic valve prosthesis with a functionally bicuspid aortic valve and ascending aortic aneurysm.

In recent years, catheter-based aortic valve interventions have become established procedures for the treatment of high-risk and advanced age patients with aortic valve pathologies. One of the limitations of the widespread applicability of this procedure is the annulus size. Until recently, no prosthesis was available to treat patients with a large annulus. We report on a patient with high-grade aortic stenosis (AS) and a 27-mm annulus, who underwent transapical implantation (TAP) of an Edwards SAPIEN® 29-mm prosthesis (Edwards LifeScience, Irvine, CA, USA). Due to insufficient dilation of his heavily calcified, functionally bicuspid aortic valve leaflets during balloon aortic valvuloplasty (BAV), the TAP prosthesis did not anchor adequately. This was determined during follow-up as he developed progressive aortic insufficiency and orthopnea, and an echocardiography revealed that the valve had been displaced into the LVOT. A conventional aortic valve replacement and ascending aorta replacement were performed, at which time the TAP prosthesis was removed. The patient recovered uneventfully, and was discharged with a well-functioning aortic bioprosthetic valve and in good general condition.

Activation of cardiomyocytes depending on their proximity to human bone marrow stem cells.

Our study aimed to elucidate whether bone marrow stem cell (BMC) treatment might result in a cellular response in cardiomyocytes IN VITRO. Subconfluent neonatal rat cardiomyocyte cultures were cocultured for three days with Vybrant CM-DiI labeled BMC from human sternal bone marrow and underwent immunohistological staining for the proto-oncogene c-Myc and the cell cycle proteins CDK2, CDK4 and ATF-3. ß-adrenoceptor density was analyzed using [125I]-iodocyanopindolol (ICYP) histoautoradiography. Quantitative analysis of immunohistochemical images revealed significantly increased expression and upregulation of c-Myc, and its downstream targets ATF-3, CDK2 and CDK4 in neighboring cardiomyocytes to BMC, depending on their distance to the BMC compared to cardiomyocytes far from the BMC. Histoautoradiography revealed a significantly higher ß-adrenoceptor density in cardiomyocytes in the immediate vicinity to the BMC. With increasing distance to the BMC, ß-adrenoceptor density in cardiomyocytes declined. Thus, a small number of BMC can affect a larger number of cardiomyocytes by activating an intracellular signaling cascade and enhancing ß-adrenoceptor density.

"Anaortic" off-pump coronary artery bypass grafting significantly reduces neurological complications compared to off-pump and conventional on-pump surgery with aortic manipulation.

OBJECTIVE: Most studies comparing off-pump coronary artery bypass grafting (OPCAB) with conventional on-pump coronary artery bypass grafting (ONCAB) include patients with aortic manipulation in the OPCAB group. Performing OPCAB without aortic manipulation, i.e., "anaortic" OPCAB (anOPCAB), may improve neurological outcome. METHODS: We reviewed the perioperative data of all isolated CABG patients at two metropolitan hospitals for the period from January 2002 to December 2007. Multiple logistic regression analysis was performed to determine whether the type of procedure was an independent predictor of adverse neurological outcome. RESULTS: Out of a total of 3699 consecutive patients, 1346 were anOPCAB, 600 OPCAB and 1753 ONCAB cases. Neurological complications occurred in 0.9 % of all patients. Compared to the anOPCAB group, there was a statistically significant higher odds for neurological complications in the OPCAB group [odds ratio (OR) 7.01, 95 % confidence interval (CI) 1.4-35.0, P = 0.0175] and in the ONCAB group (OR 12.33, 95 % CI 2.9-52.2, P = 0.0007). CONCLUSIONS: In this series "anaortic" OPCAB surgery significantly decreases the risk of neurological complications compared to both ONCAB and OPCAB with aortic manipulation. If possible, we advocate avoiding aortic manipulation in OPCAB surgery.

Inhibition of caspase-3 differentially affects vascular smooth muscle cell apoptosis in the concave versus convex aortic sites in ascending aneurysms with a bicuspid aortic valve.

Apoptosis of vascular smooth muscle cells (VSMCs) is involved in bicuspid aortic valve (BAV) ascending aorta aneurysms characteristically affecting the convex site. Caspase-3 is a pivotal effector of the apoptosis machinery. The aim of this study was to investigate the impact of an inhibited caspase-3 pathway on apoptosis in convex and concave sites VSMCs of ascending aortic tissue in vitro. Specimens from the convex and concave sites of ascending aortic aneurysm were collected from nine patients with BAV (mean age 58.7+/-14.8). Cultured VSMCs were characterized morphologically and immunohistochemically. Apoptosis activity was measured in VSMCs using Annexin V-APC with propidium iodide nuclear staining in flow cytometry. To investigate apoptotic modulation, caspase-3 was inhibited by N-acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO). Apoptosis was initiated by calcium chloride. Inhibition of caspase-3 with Ac-DEVD-CHO protected VSMCs against calcium chloride apoptosis significantly more in the concave site than in the convex site (25.8+/-9.8 versus 38.5+/-8.0% apoptotic cells, p=0.01). Morphological scanning using light microscopy revealed typical VSMCs. We provide evidence that VSMCs show a different behavior with respect to apoptosis in the concave versus the convex sites in BAV ascending aortic aneurysm. Inhibition of caspase-3 resulted in a significantly increased protection of VSMCs against apoptosis in the concave site compared with the convex site in ascending aortic aneurysm in BAV. These findings may have some implications on understanding aneurysmal formation and its potential modulation.

Rate of paraplegia and mortality in elective descending and thoracoabdominal aortic repair in the modern surgical era.

BACKGROUND: The risk of paraplegia and hospital death is the major concern in the surgical repair of descending and thoracoabdominal aortic pathologies. For specific indications, the evolving technology of endovascular stent grafting is becoming increasingly popular. We reviewed our results for elective surgical repair of various aortic pathologies with respect to this innovative therapeutic background. METHODS: From July 1993 to April 2006, 56 patients (mean age 55+/-16 years, range 25 to 80 years, 62.5% males) underwent elective surgical repair of the descending (n=37, 66.1%) and thoracoabdominal aorta (n=19, 33.9%), including seven reoperations and five cases of previous endovascular stent grafting. The underlying pathologies were: degenerative aneurysm (n=21), type B aortic dissection (n=24), and Marfan's syndrome with a chronic type B dissection and an increase in the diameter of the descending aorta (n=11), respectively. Most patients were operated using deep hypothermic circulatory arrest. RESULTS: Thirty-day mortality was 5.4 % (n=3). Two patients died of myocardial infarction, one after coronary stent occlusion. Another patient died due to ventricular disruption at the side of the left ventricular apical vent. The rate of paraplegia was 3.6% (n=2) with one case of complete and one of incomplete paraplegia. Survival at five years was 78%. CONCLUSIONS: If modern surgical principles are used in elective descending and thoracoabdominal aortic repair, surgery can be performed with a low postoperative risk for hospital death or paraplegia. These results should be taken into account when evaluating alternative therapeutic strategies in patients with similar pathologies.

Goal-directed hemodynamic optimization in high-risk cardiac surgery patients: a tale from the past or a future obligation?

The present manuscript summarizes the available evidence on outcome-related hemodynamic variables and ''goal-directed hemodynamic optimization'' strategies in patients undergoing cardiac surgery.

Types of reconstructive surgery of the aortic valve.

The aortic valve is part of the aortic root which is wedged between the heart and the ascending aorta, maintaining a directional flow throughout life-span. Beside different types of aortic valve replacements, reconstructive techniques are increasingly performed to restore normal aortic valve function. To apply these operations, understanding of normal and pathological valve anatomy and physiology is of basic importance. In addition, a widely accepted uniform aortic valve and root terminology is desirable for a proper scientific communication. Reconstructive techniques themselves can be divided into isolated reconstruction of aortic valve/root structures and the isolated replacement of one or more structures. Examples for the former ones are commissurotomy, cusps plication, decalcification or extension as well as plications of other aortic root structures (i.e. the intercusp triangles or the basal annulus). Examples for the latter ones are the remodeling and reimplantation techniques and their modifications. Replacement of the ascending aorta at the sinotubular level for the adjustment of the commissures to restore aortic root geometry also belongs to this group of techniques for aortic valve reconstruction. In this review article a systematic description of the current reconstructive techniques to restore adequate aortic valve function as well as clinical data are presented.

High myocardial lactate concentration is associated with poor myocardial function prior to cardiopulmonary bypass.

AIM: This study was designed to analyse the relationship between myocardial lactate--determined by microdialysis--and hemodynamics during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: Twenty consecutive patients with coronary artery disease were enrolled for this prospective, observational study. Microdialysis measurements were performed in the apical region of the heart during periods of 15 to 20 min before, during, and after CPB; hemodynamics and plasma lactate concentrations were determined correspondingly. Correlation analysis revealed a relationship between myocardial lactate concentration and right ventricular ejection fraction at baseline (Spearman's r: 0.6; P=0.02). Patients were thus grouped according to the myocardial lactate concentration at baseline into a high-lactate group (2.5+/-0.7 mmol.l(-1), n=10) and low-lactate group (0.9+/-0.5 mmol.l(-1), n=10). RESULTS: Preoperative left ventricular ejection fraction was not different between the groups (high-lactate group: 53+/-16%; low-lactate group: 57+/-15%; P=n.s.) Patients in the high-lactate-group had a lower stroke volume index (P=0.005) and right ventricular ejection fraction (P=0.04) before, and higher central venous and pulmonary artery pressures (P<0.01) after CPB. Plasma lactate was significantly higher during CPB in the high-lactate-group (P<0.05). No correlation was observed between myocardial and plasma lactate. Six patients in the high-lactate but none in the low-lactate-group needed inotropic support after weaning from CPB (P=0.01). CONCLUSIONS: These data are suggestive of an association between subtle myocardial ischemia--detected by microdialysis--and perioperative myocardial dysfunction in patients undergoing CABG. The microdialysis technique may be a valuable adjunct for monitoring myocardial metabolism during cardiac surgery.

[Retrograde type A dissection after endovascular stent grafting of type B dissection]. / Retrograde Typ-A-Dissektion nach endovaskulärem Stentgrafting einer Typ-B-Dissektion.

Acute aortic dissection is a disease with high mortality. Whereas acute dissection of the ascending aorta (Standford type A) is treated surgically, acute dissection of Stanford type B (descending aorta) is principally treated conservatively, but surgically in case of complications. Recently, another therapeutical option for the treatment of type B dissection has been developed using endovascular stent-grafts. We report on a 64-year-old woman with typical signs of acute aortic dissection. Computer tomography and transesophageal echocardiography demonstrated Stanford type B dissection. The patient was treated with an endovascular stent-graft, because of malperfusion of the right leg and chest pain. After successful closure of the entry by the stent, the patient developed acute right-sided hemiplegia one day after the intervention due to retrograde dissection into the aortic arch and ascending aorta. Upon immediate operation, the origin of the initially type B dissection was still sufficiently occluded by the endovascular stent-graft; however, there was another entry between the innominate artery and the left carotic artery near one proximal end of the stent's strut. Using deep hypothermia and selective antegrade cerebral perfusion, the ascending aorta and proximal arch were replaced with a 28 mm Dacron-Velour tube and the aortic root was remodelled with a tongue-shaped Dacron graft preserving the valve cusps according to a modified Yacoub procedure. After the operation, neurological symptoms diminished and the patient could walk on the ward on day eleven. This case demonstrates retrograde type A dissection as a complication after interventional treatment of type B dissection using an endovascular stent-graft. The reason for this delayed complication is speculative. Aortic wall damage during stent inserting could be a possible cause. It is also likely that the patient initially had type B dissection with retrograde dissection of the distal part of the aortic arch. Therefore, one of the straight struts of the proximal end of the stent may have caused additional damage to the vulnerable dissected aortic wall in the arch, leading to retrograde type A dissection. Careful patient selection, detailed diagnosis of the aortic arch, improved stent designs and materials, especially regarding the stent's ends and careful insertion of the stent into the aortic arch, could contribute to prevention of the described problems.

Epicardial haematoma: rare cause of acute myocardial ischaemia.

Pericardial effusion and coronary dissection are well known complications of percutaneous transluminal coronary angioplasty (PTCA). We report a rare case of sub-epicardial haematoma after PTCA, leading to local compression and cardiogenic shock. We discuss the successful management of this problem.

Biological mechanisms influencing the function of the aortic root.

Optimal function of the aortic root relies upon the ability of its component structures to move in a coordinated fashion. Some of the cells that make up the structures of the aortic root have been shown to contain nerves, receptors, and contractile elements. The ability to contract or relax may contribute to the successful function of the valve by allowing it to move in a coordinated manner in response to biological stimuli. It is known that cusp tissue receives primary, sensory, and autonomic nerves, suggesting a role for neuronal regulation of cusp function. In addition, cusp tissue has been shown to express a wide variety of receptors and to contract to a range of common vasoactive agents. The cells that constitute the valve have also shown secretory and proliferative responses. The biological signals that mediate the cross-talk between the different parts of the root have not been established. This review will examine the mechanisms that have been documented to be present and to assess their potential contribution in affecting aortic valve function.

Survival after transmyocardial laser revascularization in relation to nonlasered perfused myocardial zones.

BACKGROUND: Transmyocardial laser revascularization for severe diffuse coronary artery disease reduces angina significantly. The effect on survival, however, is questionable, and risk factors are not adequately addressed. Considering that transmyocardial laser revascularization channels do not remain patent for improving direct myocardial blood supply, other variables such as perfusion through open native or grafted vessels in remote non-transmyocardial laser revascularization areas are probably more important for survival. This hypothesis is the subject of the study. METHODS: Transmyocardial laser revascularization was performed with a CO2 laser system in 63 patients between October 1995 and December 1997. Patients received transmyocardial laser revascularization alone or in combination with coronary artery bypass grafting. The heart was divided into three perfusion zones as determined by the three major coronary arteries. Patients were divided into three groups according to the number of zones that were perfused by either a native coronary artery or a patent bypass graft: group 1 (n = 9), none; group 2 (n = 24), one; and group 3 (n = 30), two. Follow-up was performed at 3, 6, 12, 24, and 36 months and was 100% complete. Mean latest follow-up was 26.2 months, minimal follow-up of survivors was at least 12 months. RESULTS: Overall mortality was remarkably higher in group 1 (77.8%) compared with group 2 (20.8%, p = 0.005) and group 3 (13.3%, p = 0.001). Hospital mortality was 22.2% in group 1, 0% in group 2, and 3.3% in group 3. Late mortality was also higher in group 1 (55.5% versus 20.8%, and versus 9.9%, respectively). Cardiac deaths were more frequent in group 1 (55.5% versus 12.5% in group 2, p = 0.02, and versus 9.9% in group 3, p = 0.009). The number of perfused myocardial zones showed a significant influence for survival (p = 0.002). CONCLUSIONS: These data give some directional evidence that survival seems to be beneficially affected by the number of nonlasered perfused myocardial zones through native vessels or grafts in patients undergoing transmyocardial laser revascularization.

Influence of 5-hydroxytryptamine on aortic valve competence in vitro.

BACKGROUND AND AIM OF THE STUDY: The contraction of cusp tissue has been implicated to play a role in aortic valve function. The effect of the contractile agent 5-hydroxytryptamine (5-HT) on the competence of isolated aortic roots has been assessed, and the vasomotor properties of 5-HT on aortic root tissue examined. METHODS: Isolated porcine aortic roots were pressurized with Kreb's solution through the aortic arch. 5-HT was added in increasing concentrations (10(-7) to 10(-5) M) and the degree of leakage measured over time. In additional experiments, portions of sinotubular junction, sinus, annular and cusp tissue were set up in organ baths, placed under tension, and challenged with 5-HT (10(-9) to 10(-5) M). Viability of each valve structure was assessed by addition of KCl (90 mM). RESULTS: The rate of leakage from intact aortic roots increased when 10(-6) and 10(-5) M 5-HT was added. The maximum effect, observed at 10(-5) M 5-HT, was equal to an increase of 61.8+/-23.0% above control (p <0.05). The perfusion pressure at each concentration of 5-HT was unchanged. This response was inhibited by the 5-HT2A receptor antagonist ketanserin. Addition of KCl to isolated valve structures gave a mean contractile response of 0.8+/-0.1mN for cusp, 19+/-11.0 mN for annular, 29+/-8.0 mN for sinus, and 23+/-8.0 mN for sinotubular junction tissue (each n = 4). Only cusp tissue contracted when treated with 5-HT, with a maximum 105.5+/-17.2% (n = 4) of the response to KCl. The response to 5-HT was blocked by the 5-HT2A-receptor antagonist ketanserin at 10(-6) M (n = 4). None of the other aortic root structures responded to 5-HT. CONCLUSION: These results show that 5-HT influences the competence of isolated porcine aortic valves. This effect is contributed by contraction of the cusp tissue, and is mediated by 5-HT2A receptors. These effects may contribute to the association between valve dysfunction, 5-HT and certain appetite suppressants.

Receptor-mediated contraction of aortic valve leaflets.

BACKGROUND AND AIM OF THE STUDY: The mechanisms that regulate the function of the aortic valve are not fully understood. Cusp tissue has been shown to have contractile properties, but little is known as to which receptors mediate these effects. METHODS: We have examined, using isolated organ baths, the response of porcine aortic valve leaflets to a range of vasoactive agents including endothelin-1, noradrenaline, adrenaline, the thromboxane (TX) A2 mimetic U46619, 5-hydroxytryptamine (5-HT), histamine and angiotensin II. The viability of each individual leaflet was tested by the addition of 90 mM KCl. RESULTS: All agents tested, with the exception of angiotensin II, were capable of inducing concentration-dependent contractions of the valve leaflets. The responses to endothelin-1 and U46619 were significantly greater than those of all the other agents tested. Responses to endothelin-1 could be inhibited by 10(-5) M of the mixed ET(A/B) receptor antagonist bosantan. The response to both catecholamines was blocked by 10(-6) M yohimbine, but not by 3 x 10(-7) M prazosin, indicating the presence of alpha2-adrenoceptors. The response to histamine was mediated exclusively by H1-receptors, as judged by the antagonistic effect of 10(-6) M of the H1-receptor antagonist mepyramine. The response to 5-HT could be blocked by 10(-6) M of the 5-HT2A-receptor antagonist ketanserin, and that of U46619 by 10(-6) M of the TXA2-receptor antagonist SQ30741. CONCLUSION: These results demonstrate the range of receptor systems that can mediate contraction of aortic valve leaflets. Further studies are required to elucidate the role of these receptors in the physiology and pathophysiology of the aortic valve.

The aortic outflow and root: a tale of dynamism and crosstalk.

Although the aortic outflow and root (AoR) constitute a short channel connecting the left ventricle to the aorta, its different components have been shown to be highly specialized structures, interacting with each other as well as with surrounding structures, thus providing a "tale of dynamism and crosstalk." Thorough knowledge of the AoR and morphological and structural changes, that occur during pathological processes, can have important implications in evolving and executing surgical procedures designed to preserve and restore the "dynamism and crosstalk." The crown-shaped annulus, fibrous trigones, aortic cusps components, aortic sinuses, and the sinotubular junction share a dynamic coordinated behavior, which can be partially or completely restored in various repair or replacement procedures of the AoR. The interaction and the specific operations are presented with evidence supporting the notion that the dynamic behavior of the root does influence the pattern of instantaneous movements of the aortic cusps after different types of operations. Further studies are required to evaluate the influence of adopting these ideas on the long-term results of operative procedures.