Current pharmacological approach to restore endothelial dysfunction.

Endothelial dysfunction is characterized by an impairment of endothelium-dependent vasodilatation. It has been linked to each of the known atherogenic risk factors, including diabetes mellitus, hypertension, dyslipidaemia, cigarette smoking, menopause, etc. A number of recent studies have shown that the severity of endothelial dysfunction correlates with the development of coronary artery disease and predicts future cardiovascular events. Therefore, these findings strengthen the hypothesis that endothelial dysfunction may be an early stage of coronary atherosclerosis. This phenomenon primarily reflects an imbalance between the vasodilating (nitric oxide) and vasoconstrictor agents (endothelin-1). Several invasive (intracoronary or intrabrachial infusions of vasoacting agents) and non-invasive techniques (assessment of flow mediated vasodilatation in the brachial artery by ultrasound) have been developed during the last few years to evaluate endothelial function in the coronary and peripheral circulation. This new methodology has allowed assessing the severity of the abnormalities in vascular function and their regression by several pharmacological and non-pharmacological interventions. It is likely that restoration of endothelial function can regress the atherosclerotic disease process and prevent future cardiovascular events. Most pharmacological interventions attempting to improve endothelial dysfunction targeted the risk factors linked to endothelial dysfunction: hypertension (ACE-inhibitors, calcium antagonists), dyslipidaemia (lipid-lowering agents) and menopause (estrogens). Nevertheless, several pharmacological agents have been suggested to achieve vascular protection through different mechanisms beyond their primary therapeutic actions: ACE-inhibitors, statins, third generation of beta-blockers (nebivolol), endothelium-derived nitric oxide synthesis (tetrahydrobiopterin, BH4) and antioxidants agents. In this review we will focus on the current pharmacological management of the endothelial dysfunction.

Pharmacological approach of no-reflow phenomenon related with percutaneous coronary interventions.

The no-reflow phenomenon (NRP) is characterized by an inadequate myocardial tissue perfusion in the presence of a patent epicardial coronary artery. It generally occurs after temporary occlusion of the artery causing myocardial ischemia and necrosis that persist after relief of the vessel occlusion, without evidence of epicardial mechanical obstruction. Currently, the main scenario of NRP is the setting of percutaneous coronary interventions (PCI), especially in patients with acute myocardial infarction or saphenous vein graft disease, and its occurrence is associated with adverse clinical outcomes. Pathophysiology of NRP is not fully understood but it seems to be related with microvascular damage. Several mechanisms have been involved, such as distal microembolization, interstitial and intracellular edema, coronary spasm and capillary plugging. Diagnosis of NRP is generally based on clinical and angiographic data. Several methods have been proposed for the assessment of NRP, such as electrocardiography, myocardial contrast echocardiography, contrast-enhanced magnetic resonance imaging, nuclear imaging or positron emission tomography, that have demonstrated additional prognostic value over angiography. There are different pharmacological and mechanical approaches for the prevention of NRP but none of them have demonstrated a clear efficacy. The treatment of established NRP is mainly based on the administration of coronary vasodilators, like adenosine, verapamil or nitroprusside, but clinical results are frequently disappointing. The objective of this review is to describe the state of the art of the pathophysiology, diagnosis and pharmacological management of NRP.

[Variable response to the biological inhibition of platelets by abciximab in patients subjected to percutaneous coronary angioplasty]. / Respuesta variable a la inhibición biológica de las plaquetas por abciximab en pacientes sometidos a revascularización coronaria percutánea.

INTRODUCTION AND OBJECTIVES: Abciximab has been shown to reduce the risk of thrombotic complications during coronary angioplasty, however there are still many aspects to be resolved. The aim of this study was to investigate the various biological effects of abciximab on platelets during coronary angioplasty. METHODS: The degree of platelet inhibition (with 5 and 20 mol/l concentrations of ADP), occlusion time (measurement of platelet haemostatic capacity, PFA-100), and the platelet activation markers were determined in 15 patients who underwent basal coronary angioplasty and abciximab treatment. Determinations were obtained before, 15 minutes after procedure initiation, at procedure termination, and 24 hours after procedure termination. RESULTS: More than 80% platelet aggregation inhibition was observed in 13 patients during the procedure, but after 24 hours (p < 0.05) was only detected in two. The occlusion time during the procedure was > 300 sec. in 13 patients, 6 of whom evolved to normal values after 24 hours (p < 0.05). A high correlation (p = 0.02) was found between these two parameters during the intervention, but not after 24 hours. No platelet inhibition or occlusion time changes were observed in 2 patients during the study. The expression of p-selectin increased significantly during the procedure (p < 0.05). CONCLUSIONS: The variability of platelet function inhibition and existence of circulating activation during coronary angioplasty following the administration of abciximab support the use of early analytical controls with the objective of modifying guidelines for use in order to optimize its effect or to combine it with other antithrombotic agents.

[Aortic pseudocoarctation complicated by a giant pseudoaneurysm]. / Seudocoartación de aorta complicada con seudoaneurisma gigante.

Pseudocoarctation of the aorta is an infrequent anomaly caused by the elongation and the congenital kinking of the aorta. We present a case of pseudocoarctation of the aorta with saccular aneurysm complicated with a large pseudoaneurysm. Both, magnetic resonance and aortography showed an aneurysm of the aortic isthmus that extended/progressed as pseudoaneurysm towards the neck. The patient was asymptomatic but due to the high risk of rupture, she underwent surgical reparation. The revision of the literature and our experience with this case show that pseudocoarctation of the aorta is not always a benign pathology and that surgical reparation should be performed in all those cases that are complicated by aneurysm.

[Biventricular diverticulosis associated with rheumatic heart disease: apropos of a case]. / Diverticulosis biventricular asociada a cardiopatía reumática: a propósito de un caso.

We report a case of a 58-year-old woman with rheumatic mitral stenosis scheduled for percutaneous valvuloplasty. Prior left and right ventricular angiograms showed multiple diverticula at left ventricular apical and diaphragmatic walls and right ventricular diaphragmatic wall. Chest x-ray and echocardiogram were normal. Magnetic resonance imaging was concordant with catheterization findings and ruled out other cardiac malformations. The risk of ventricular perforation changed our indication of percutaneous valvuloplasty in favor of open heart commissurotomy.

[Parasitic delirium in patient with multiorganic pathology: a complex situation]. / Delirio parasitario en paciente con patología multiorgánica: una compleja situación.

Delusion of parasitosis is often observed in people who usually take psychoactive drugs. Moreover, it can be present in infectious diseases or tumours of the central nervous system, metabolic disorders, deficiency and states systemic disorders, such as Systemic Lupus Erythematosus (SLE). The neuropsychiatric manifestations in SLE patients are common and constitute one of the criteria for the classification of SLE. Presentation as an acute organic mental syndrome is a clinical emergency and it is usually required the admission in the hospital. We report a case of delusion of parasitosis in a middle age woman diagnosed of SLE several years before and with previous corticosteroid therapy, right temporal arachnoid cyst, chronic Lyme disease and hypothyroidism. We analyse the different role of each pathology and the clinical practice difficulties in the management of these disorders.