A novel anti-ischemic nitric oxide donor (LA419) reduces thrombogenesis in healthy human subjects.

BACKGROUND: Platelet and endothelial production of nitric oxide (NO) is known to be impaired in coronary artery disease patients. Compounds that release NO (e.g. nitrates) have antiplatelet effects, but at supratherapeutic doses with hypotensive side effects. OBJECTIVES: To investigate the antithrombotic effect on human blood of a novel NO donor (LA419) with known anti-ischemic properties but without hypotensive side effects and to compare with abciximab. PATIENTS/METHODS: Healthy subjects (n = 8; 32 +/- 3 years) received daily aspirin starting three days prior to the study day. Treatments (LA419 10 and 20 microm, and abciximab 4 microm) were added ex vivo to non-anticoagulated blood, and the antithrombotic properties were assessed by measuring changes in thrombus size from pretreatment baseline in the Badimon perfusion chamber at low and high shear rates. Platelet surface adhesion using a Cone and Platelet Analyzer (CPA) and platelet fibrinogen-receptor activation with flow cytometry were also evaluated. RESULTS: At low shear rates, LA419 displayed a reduction in thrombus area of 43% +/- 8% (10 microm) and 56% +/- 6% (20 microm), whereas at high shear rates the reductions were 44% +/- 3% (10 microm) and 62% +/- 6% (20 microm). Platelet surface adhesion with the CPA was also reduced. Abciximab exhibited a strong inhibitory effect on thrombus formation, platelet surface adhesion and fibrinogen receptor activation. CONCLUSIONS: The novel NO donor, LA419, shows a strong antithrombotic effect in human blood, which is comparable to abciximab, especially under high shear rate conditions. Our observations suggest that the availability of an NO donor could prove beneficial in the prevention of thrombotic complications of cardiovascular disease. Further clinical studies are warranted.

Human brain mapping of auditory imagery: event-related functional MRI study.

We used event-related fMRI methodology to investigate human brain activity during auditory imagery. A series of susceptibility-weighted MR images covering the whole brain were acquired to obtain blood oxygenation level-dependent (BOLD) signal changes associated with the imagery event of hearing simple monotone. Group analysis across the 12 right-handed subjects revealed activations in the medial and inferior frontal gyri, precuneus, middle frontal gyri, superior temporal gyri, and anterior cingulate gyri. Bilateral primary and secondary auditory areas in the superior temporal gyri also exhibited the event-related MR signal changes. The proposed method allowed for the analysis of brain areas responsive to the event of auditory imagery while our results suggest that auditory imagery and actual audition share common neural substrates.