Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning.

Preconditioning with sublethal ischemia protects against neuronal damage after subsequent lethal ischemic insults in hippocampal neurons. A pharmacological approach using agonists and antagonists at the adenosine A1 receptor as well as openers and blockers of ATP-sensitive K+ channels has been combined with an analysis of neuronal death and gene expression of subunits of glutamate and gamma-aminobutyric acid receptors, HSP70, c-fos, c-jun, and growth factors. It indicates that the mechanism of ischemic tolerance involves a cascade of events including liberation of adenosine, stimulation of adenosine A1 receptors, and, via these receptors, opening of sulfonylurea-sensitive ATP-sensitive K+ channels.

Oxygen-sensitive calcium channels in vascular smooth muscle and their possible role in hypoxic arterial relaxation.

We have investigated the modifications of cytosolic [Ca2+] and the activity of Ca2+ channels in freshly dispersed arterial myocytes to test whether lowering O2 tension (PO2) directly influences Ca2+ homeostasis in these cells. Unclamped cells loaded with fura-2 AM exhibit oscillations of cytosolic Ca2+ whose frequency depends on extracellular Ca2+ influx. Switching from a PO2 of 150 to 20 mmHg leads to a reversible attenuation of the Ca2+ oscillations. In voltage-clamped cells, hypoxia reversibly reduces the influx of Ca2+ through voltage-dependent channels, which can account for the inhibition of the Ca2+ oscillations. Low PO2 selectively inhibits L-type Ca2+ channel activity, whereas the current mediated by T-type channels is unaltered by hypoxia. The effect of low PO2 on the L-type channels is markedly voltage dependent, being more apparent with moderate depolarizations. These findings demonstrate the existence of O2-sensitive, voltage-dependent, Ca2+ channels in vascular smooth muscle that may critically contribute to the local regulation of circulation.

Trends in Socioeconomic Inequalities in Ischemic Heart Disease Mortality in Small Areas of Nine Spanish Cities from 1996 to 2007 Using Smoothed ANOVA

The aim of this study was to analyze the evolution of socioeconomic inequalities in mortality due to ischemic heart diseases (IHD) in the census tracts of nine Spanish cities between the periods 1996–2001 and 2002–2007. Among women, there are socioeconomic inequalities in IHD mortality in the first period which tended to remain stable or even increase in the second period in most of the cities. Among men, in general, no socioeconomic inequalities have been detected for this cause in either of the periods. These results highlight the importance of intra-urban inequalities in mortality due to IHD and their evolution over time.

Blood markers and recurrence of stroke in patients with transient ischemic attack

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Anxiety and depression symptoms in liver encephalopathy : are they psychiatric or organic?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

Ablation of ischemic ventricular tachycardia: evidence, techniques, results, and future directions

PURPOSE OF REVIEW This article summarizes current understanding of the arrhythmia substrate and effect of catheter ablation for infarct-related ventricular tachycardia, focusing on recent findings. RECENT FINDINGS Clinical studies support the use of catheter ablation earlier in the course of ischemic disease with moderate success in reducing arrhythmia recurrence and shocks from implantable defibrillators, although mortality remains unchanged. Ablation can be lifesaving for patients presenting with electrical storm. Advanced mapping systems with image integration facilitate identification of potential substrate, and several different approaches to manage hemodynamically unstable ventricular tachycardia have emerged. Novel ablation techniques that allow deeper lesion formation are in development. SUMMARY Catheter ablation is an important therapeutic option for preventing or reducing episodes of ventricular tachycardia in patients with ischemic cardiomyopathy. Present technologies allow successful ablation in the majority of patients, even when the arrhythmia is hemodynamically unstable. Failure of the procedure is often because of anatomic challenges that will hopefully be addressed with technological progress.

Sleep-disordered breathing among acute ischemic stroke patients in Brazil.

OBJECTIVES Sleep-disordered breathing (SDB) is very common in acute stroke patients and has been related to poor outcome. However, there is a lack of data about the association between SDB and stroke in developing countries. The study aims to characterize the frequency and severity of SDB in Brazilian patients during the acute phase of ischemic stroke; to identify clinical and laboratorial data related to SDB in those patients; and to assess the relationship between sleep apnea and functional outcome after six months of stroke. METHODS Clinical data and laboratorial tests were collected at hospital admission. The polysomnography was performed on the first night after stroke symptoms onset. Functional outcome was assessed by the modified Rankin Scale (mRS). RESULTS We prospectively evaluated 69 patients with their first-ever acute ischemic stroke. The mean apnea-hypopnea index (AHI) was 37.7 ± 30.2. Fifty-three patients (76.8%) exhibited an AHI ≥ 10 with predominantly obstructive respiratory events (90.6%), and thirty-three (47.8%) had severe sleep apnea. Age (OR: 1.09; 95% CI: 1.03-1.15; p= 0.004) and hematocrit (OR: 1.18; 95% CI: 1.03-1.34; p= 0.01) were independent predictors of sleep apnea. Age (OR: 1.13; 95% CI: 1.03-1.24; p= 0.01), body mass index (OR: 1.54; 95% CI: 1.54-2.18; p= 0.01), and hematocrit (OR: 1.19; 95% CI: 1.01-1.40; p= 0.04) were independent predictors of severe sleep apnea. The National Institutes of Health Stroke Scale (NIHSS; OR: 1.30; 95% CI: 1.1-1.5; p= 0.001) and severe sleep apnea (OR: 9.7; 95% CI: 1.3-73.8; p= 0.03) were independently associated to mRS >2 at six months, after adjusting for confounders. CONCLUSION Patients with acute ischemic stroke in Brazil have a high frequency of SDB. Severe sleep apnea is associated with a poor long-term functional outcome following stroke in that population.