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MMRL also performs contract research using a mulit - level
screening approach to identify active agents and to assess
their efficacy and mechanisms of action from within existing
chemical libraries.
Level I:
Proprietary, ultra - high level throughput fluorometric enzymatic
assays are available to identify active agents at specific
biochemical targets that MMRL has determined are involved
in the modulation of energy metabolism.
Level II:
Active compounds undergo further trials to confirm their selectivity
and efficacy using high throughput biochemical assays in intact
cell systems.
Level III:
New evaluation of lead compounds in intact, perfused organs
to quantify their efficacy and anti - ischemic mechanisms.
Pioneered by MMRL, this experimental approach employs intact
working hearts perfused under appropriate conditions of myocardial
energy supply and demand.
This system allows the study of both mechanical (heart rate,
aortic pressure, coronary flow, aortic outflow, cardiac output,
contractility) and metabolic (MVO2, glycolysis, glucose, and
fatty acid oxidation rates) function and cardiac efficiency
continuously throughout aerobic perfusion, or during and following
graded periods of controlled ischemia.
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