The role of epoxyeicosatrienoic acids in the cardiovascular system.

There is increasing evidence suggesting that epoxyeicosatrienoic acids (EETs) play an important role in cardioprotective mechanisms. These include regulating vascular tone, modulating inflammatory responses, improving cardiomyocyte function and reducing ischaemic damage, resulting in attenuation of animal models of cardiovascular risk factors. This review discusses the current knowledge on the role of EETs in endothelium-dependent control of vascular tone in the healthy and in subjects with cardiovascular risk factors, and considers the pharmacological potential of targeting this pathway.

Spinal cord injury models: a review.

BACKGROUND: Animal spinal cord injury (SCI) models have proved invaluable in better understanding the mechanisms involved in traumatic SCI and evaluating the effectiveness of experimental therapeutic interventions. Over the past 25 years, substantial gains have been made in developing consistent, reproducible and reliable animal SCI models. STUDY DESIGN: Review. OBJECTIVE: The objective of this review was to consolidate current knowledge on SCI models and introduce newer paradigms that are currently being developed. RESULTS: SCI models are categorized based on the mechanism of injury into contusion, compression, distraction, dislocation, transection or chemical models. Contusion devices inflict a transient, acute injury to the spinal cord using a weight-drop technique, electromagnetic impactor or air pressure. Compression devices compress the cord at specific force and duration to cause SCI. Distraction SCI devices inflict graded injury by controlled stretching of the cord. Mechanical displacement of the vertebrae is utilized to produce dislocation-type SCI. Surgical transection of the cord, partial or complete, is particularly useful in regenerative medicine. Finally, chemically induced SCI replicates select components of the secondary injury cascade. Although rodents remain the most commonly used species and are best suited for preliminary SCI studies, large animal and nonhuman primate experiments better approximate human SCI. CONCLUSION: All SCI models aim to replicate SCI in humans as closely as possible. Given the recent improvements in commonly used models and development of newer paradigms, much progress is anticipated in the coming years.

Increased incidence of interatrial block in younger adults with cryptogenic stroke and patent foramen ovale.

BACKGROUND: Stroke is often unexplained in younger adults, although it is often associated with a patent foramen ovale (PFO). The reason for the association is not fully explained, and mechanisms other than paradoxical embolism may be involved. Young stroke patients with PFO have more atrial vulnerability than those without PFO. It is plausible that stretching of the interatrial septum may disrupt the interatrial conduction pathways causing interatrial block (IAB). IAB is associated with atrial fibrillation, dysfunctional left atria and stroke. METHODS: Electrocardiogram (ECG) characteristics of prospectively recruited young patients (≤55 years of age) with unexplained stroke (TOAST and A-S-C-O) were compared with control data. All stroke cases underwent bubble contrast transthoracic and transoesophageal echography. IAB was defined as a P-wave duration of ≥110 ms. ECG data were converted to electronic format and analysed in a blind manner. RESULTS: Fifty-five patients and 23 datasets were analysed. Patients with unexplained stroke had longer P-wave duration (p = 0.013) and a greater prevalence of IAB (p = 0.02) than healthy controls. Case status was an independent predictor of P-wave duration in a significant multivariate model. There was a significant increase in the proportion of cases with a PFO with IAB compared with cases without PFO and with controls (p = 0.005). CONCLUSIONS: Young patients with unexplained stroke, particularly those with PFO, exhibit abnormal atrial electrical characteristics suggesting atrial arrhythmia or atrial dysfunction as a possible mechanism of stroke.

New acute and chronic black holes in patients with multiple sclerosis randomised to interferon beta-1b or glatiramer acetate.

BACKGROUND: Hypointense lesions on T1 weighted MRI, referred to as black holes (BH), are a marker of demyelination/axonal loss in multiple sclerosis (MS). There is some evidence that glatiramer acetate (GA) may decrease the conversion of new brain lesions to BH. METHODS: Monthly 3-Tesla brain MRI scans were used for up to 2 years to study the development and evolution of new BH in 75 patients with MS randomised to GA or Interferon beta-1b (IFNbeta1b) in the BECOME study. FINDINGS: Of 1224 newly enhancing lesions (NEL) appearing at baseline through 24 months in 61 patients, 767 (62.7%) showed an acute BH (ABH). The majority of ABH were transient and of similar duration by treatment group. Of 571 ABH in which MRI follow-up scans were available for >or=1 year, 103 (18.8%) were still visible >or=12 months after onset and were considered chronic BH (CBH). Only 12.1% of the 849 NEL with MRI follow-up >or=1 year converted to CBH, 9.8% with IFNbeta1b and 15.2% with GA (p = 0.02). The conversion from ABH to CBH was also lower with IFNbeta1b (15.2%) than with GA (21.4%), of borderline significance (p = 0.06). The majority of patients who developed NEL did not develop CBH; however, about a quarter had conversion rates from ABH to CBH greater than 20%. INTERPRETATION: Only a minority of new brain lesions in patients with MS treated with GA or IFNbeta1b convert to CBH.

Efficacy of treatment of MS with IFNbeta-1b or glatiramer acetate by monthly brain MRI in the BECOME study.

BACKGROUND: There are no published MRI studies comparing interferon beta 1b (IFNbeta-1b) and glatiramer acetate (GA) for treatment of relapsing multiple sclerosis (MS). OBJECTIVE: To compare the efficacy of IFNbeta-1b and GA for suppression of MS disease activity as evidenced on frequent brain MRI. METHODS: A total of 75 patients with relapsing-remitting MS or clinically isolated syndromes were randomized to standard doses of IFNbeta-1b or GA and followed by monthly brain MRI for up to 2 years with a protocol optimized to detect enhancement. The primary outcome was the number of combined active lesions (CAL) per patient per scan during the first year, which included all enhancing lesions and nonenhancing new T2/fluid-attenuated inversion recovery (FLAIR) lesions. Secondary outcomes were the number of new lesions and clinical exacerbations over 2 years. RESULTS: Baseline characteristics were similar between the groups. The primary outcome showed similar median (75th percentile) CAL per patient per scan for months 1-12, 0.63 (2.76) for IFNbeta-1b, and 0.58 (2.45) for GA (p = 0.58). There were no differences in new lesion or clinical relapses for 2 years. Only 4.4% of CAL on monthly MRI scans were nonenhancing new T2/FLAIR lesions. CONCLUSION: Patients with relapsing multiple sclerosis randomized to interferon beta 1b or glatiramer acetate showed similar MRI and clinical activity.

Role of increased aortic stiffness in the pathogenesis of heart failure.

Aortic stiffness is an independent predictor of cardiovascular mortality in a variety of patient groups including hypertensives and other unselected patients. Despite a sound pathophysiologic basis, termed the ventricular-vascular coupling mechanism, the relationship between aortic stiffness and heart failure has been less well studied. This review summarizes some important trials of aortic stiffness in cardiovascular disease risk prediction and progression to heart failure. Emerging targets for therapeutics and areas requiring more research are also discussed.