A Myocardial Slice Culture Model Reveals Alpha-1A-Adrenergic Receptor Signaling in the Human Heart

• Model for translational studies
• Human LV slices
• Simple, high throughput, viable
• Assays signaling and contraction
• Supports viral transduction
• Useful for proof-of-concept in man
• Shows the α1A-AR functions in human heart

SummaryThe authors used 52 nonfailing and failing human hearts to develop a simple, high throughput left ventricular myocardial slice model that is stable by ATP and viability assays for at least 3 days. The model supports studies of signaling, contraction, and viral transduction. They use the model to show for the first time that the alpha-1A-adrenergic receptor, which is present at very low abundance in the human myocardium, activates cardioprotective ERK with nanomolar EC50 in failing heart slices and stimulates a positive inotropic effect. This model should be useful for translational studies, to test whether molecules discovered in basic experiments are functional in the human heart.

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