false2016-03-16T23:02:09

Oxidative stress is implicated in atherogenesis, yet most clinical trials with antioxidants, particularly vitamin E, have failed to protect against atherosclerotic diseases. A striking exception is probucol, which retards atherosclerosis in carotid arteries and restenosis of coronary arteries after angioplasty. Because probucol has in vitro cellular-protective effects independent of inhibiting lipid oxidation, we investigated the mode of action of probucol in vivo. We used three models of vascular disease: apolipoprotein E–deficient mice, a model of atherosclerosis; rabbit aortic balloon injury, a model of restenosis; and carotid injury in obese Zucker rats, a model of type 2 diabetes. Unexpectedly, we observed that the phenol moieties of probucol were insufficient, whereas its sulphur atoms were required for protection. Probucol and its sulphur-containing metabolite, but not a sulphur-free phenolic analogue, protected via cell-specific effects on inhibiting macrophage accumulation, stimulating reendothelialization, and inhibiting vascular smooth muscle cell proliferation. These processes were mediated via induction of heme oxygenase-1 (HO-1), an activity not shared by vitamin E. Our findings identify HO-1 as the molecular target of probucol. They indicate 2-electron rather than radical (1-electron) oxidants as important contributors to atherogenesis, and point to novel lead compounds for therapeutic intervention against atherosclerotic diseases.

M a i l i n g A d d r e s s : F r e d e r i c o T. U l t r a m a r i @@@@@@@@@@@@@@@@@@@@@@@@@@@ It is estimated that 6,000 and 2,000 cardiac catheterization procedures per million inhabitants/year are performed in Western countries for diagnostic and therapeutic purposes. In order to perform these procedures, 1,800 tons of iodine are required all over the world to manufacture contrast media (CM). The number of procedures that require the use of contrast media (or dye) has increased over time, and the population submitted to it is growing older, presenting more comorbidities 1, 2. Currently low-osmolar contrast media are used in approximately 75% of patients and the iso-osmolar contrast media, allegedly less toxic are becoming more popular 1. In spite of development of new contrast media, they still represent the third main cause of nosocomial-acquired acute renal failure (ARF) (10% of cases), substantially increasing hospitalization period, care costs and in-hospital morbi-mortality 3-6. The main goal is to address important aspects about the contrast-medium induced nephropathy (CMIN) that follows cardiac catheterization, including its definition, pathogenesis, incidence, risk factors, clinical picture, prevention, treatment and prognosis.

Contrast-induced encephalopathy (CIE) is an acute and reversible neurological disturbance associated with the intra-arterial administration of iodinated contrast medium during cardiac catheterisation. It may manifest with encephalopathy, motor and sensory disturbances; vision disturbances, including cortical blindness, ophthalmoplegia, aphasia; and seizures. Disruption of the blood-brain barrier and direct neuronal toxicity are believed to be implicated in the pathophysiology of the syndrome. Symptoms appear soon after contrast administration and resolve completely within 24-48 h. Risk factors may include hypertension, diabetes mellitus, renal impairment, the administration of large volumes of iodinated contrast, percutaneous coronary intervention or selective angiography of internal mammary grafts and previous adverse reaction to iodinated contrast. On cerebral imaging, CIE may mimic subarachnoid haemorrhage or cerebral ischaemia, but imaging may be normal. Prognosis is excellent with supportive management alone. CIE may recur, but re-challenge with iodinated contrast without adverse effects has been documented. CIE is a diagnosis of exclusion and is an important clinical entity to consider in the differential diagnosis of stroke following cardiac catheterisation. Physicians should be aware of it and consider it prior to initiating thrombolysis.