Method Profile
Coupled human liver and heart tissues support matched measurements of parent drug, metabolite and contraction over time.
Mechanistic investigation of metabolism-associated cardiac recovery and material-dependent drug exposure.
Human iPSC-derived engineered heart tissues with supporting stromal cells and a single batch of primary human hepatocytes in communicating compartments.
Co-culture and separate-tissue controls exposed to nominal terfenadine at 1 or 3 μM; video and medium samples at 4, 24 and 48 hours.
Human tissues
Engineered cardiac tissues and primary hepatocytes with matched monoculture controls.
Motion and chemistry
Video-based contractile analysis, LC–MS/MS of terfenadine/fexofenadine and a cell-free PDMS-support adsorption comparison.
Normalize cardiac motion to its pre-exposure baseline and compare the concentration/function time courses. Preserve the distinction between nominal and measured exposure.
Follow matched co-cultures and single-tissue systems after terfenadine exposure; evaluate adsorption separately.
Main experiments used three or four independent tissue constructs per group, one hepatocyte batch and one test drug.
Heart-only, liver-only and liver–heart cultures; cell-free support/no-support controls.
At 1 μM, co-culture recovered to baseline contraction by 48 hours while heart monoculture remained depressed; recovery at 3 μM was partial. Parent-drug loss and metabolite formation accompanied recovery.
A coupled human liver–heart system followed terfenadine, its metabolite and cardiac motion over time. Contractile recovery occurred alongside hepatic metabolism, while material adsorption and exposure level shaped the experiment.
