Comprehensive use of cardiopulmonary exercise testing identifies adults with congenital heart disease at increased mortality risk in the medium term.

Background: Parameters of cardiopulmonary exercise testing were recently identified as strong predictors of mortality in adults with congenital heart disease. We hypothesized that combinations of cardiopulmonary exercise testing parameters may provide optimal prognostic information on midterm survival in this population.

Methods And Results: A total of 1375 consecutive adult patients with congenital heart disease (age, 33±13 years) underwent cardiopulmonary exercise testing at a single center over a period of 10 years.

Loss of the astrocyte glutamate transporter GLT1 modifies disease in SOD1(G93A) mice.

Recent studies have highlighted the role of astrocytes in the development of motor neuron disease in animal models. The astrocyte glutamate transporter GLT1 is responsible for a significant portion of glutamate transport from the synaptic cleft; regulating synaptic transmission and preventing glutamate excitotoxicity. While previous studies have demonstrated reductions in GLT1 with SOD1-mediated disease progression, it is not well established whether a reduction in this astrocyte-specific transporter alters the pathobiology of motor neuron degeneration in the SOD1(G93A) mouse.

Degeneration of respiratory motor neurons in the SOD1 G93A transgenic rat model of ALS.

The transgenic mutant superoxide dismutase (SOD1) mice and rats have been important tools in attempting to understand motor neuron pathology and degeneration but the mechanism behind death in this model has not been studied. We studied the electrophysiologic and pathologic properties of the cervical motor neurons and phrenic nerves in mutant SOD1 rats and demonstrated motor neuron loss, progressive reduction of phrenic nerve compound muscle action potential amplitudes, phrenic nerve fiber loss, and diaphragm atrophy suggesting respiratory insufficiency as a significant contributing factor leading to SOD1 rat death. Unlike previous observations suggesting that a dying-back process may be occurring in the mouse model of the disease, we did not observe differences between proximal and distal axon loss in phrenic nerves of SOD1 rats.