Mechanical behaviour and rupture of normal and pathological human ascending aortic wall

The mechanical properties of aortic wall, both healthy and pathological, are needed in order to develop and improve diagnostic and interventional criteria, and for the development of mechanical models to assess arterial integrity. This study focuses on the mechanical behaviour and rupture conditions of the human ascending aorta and its relationship with age and pathologies. Fresh ascending aortic specimens harvested from 23 healthy donors, 12 patients with bicuspid aortic valve (BAV) and 14 with aneurysm were tensile-tested in vitro under physiological conditions. Tensile strength, stretch at failure and elbow stress were measured. The obtained results showed that age causes a major reduction in the mechanical parameters of healthy ascending aortic tissue, and that no significant differences are found between the mechanical strength of aneurysmal or BAV aortic specimens and the corresponding age-matched control group. The physiological level of the stress in the circumferential direction was also computed to assess the physiological operation range of healthy and diseased ascending aortas. The mean physiological wall stress acting on pathologic aortas was found to be far from rupture, with factors of safety (defined as the ratio of tensile strength to the mean wall stress) larger than six. In contrast, the physiological operation of pathologic vessels lays in the stiff part of the response curve, losing part of its function of damping the pressure waves from the heart.

TMS- EEG Signatures of GABAergic Neurotransmission in the Human Cortex

Combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) constitutes a powerful tool to directly assess human cortical excitability and connectivity. TMS of the primary motor cortex elicits a sequence of TMS-evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission through GABA-A receptors (GABAAR) modulates early TEPs (<50 ms after TMS), whereas GABA-B receptors (GABABR) play a role for later TEPs (at ∼100 ms after TMS). However, the physiological underpinnings of TEPs have not been clearly elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we tested the effects of a single oral dose of alprazolam (a classical benzodiazepine acting as allosteric-positive modulator at α1, α2, α3, and α5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly at the α1 GABAAR) in a double-blind, placebo-controlled, crossover study. In Experiment 2, we tested the influence of baclofen (a GABABR agonist) and diazepam (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam increased the amplitude of the negative potential at 45 ms after stimulation (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem increased the N45 only. In contrast, baclofen specifically increased the N100 amplitude. These results provide strong evidence that the N45 represents activity of α1-subunit-containing GABAARs, whereas the N100 represents activity of GABABRs. Findings open a novel window of opportunity to study alteration of GABAA-/GABAB-related inhibition in disorders, such as epilepsy or schizophrenia.