A flow-through infusion calorimeter for measuring muscle energetics during pharmacological interventions

We report on the design, development, and performance of a new calorimeter for measuring the heat-production and force-development of tiny samples of muscle tissue, while they are exposed to time-varying concentrations of a pharmacological agent. Fluid is delivered to a muscle sample by a syringe pump synchronized with a servo-controlled gravity-fed flow system. The rate of muscle heat production is inferred from voltages arising from a pair of thermopiles, to a resolution of approximately 6 nW, providing a signal:noise ratio of approximately 1350. We demonstrate the utility of the instrument by selectively chemically disabling and forcibly engaging the muscle's molecular force development mechanism, while measuring muscle heat-rate and force. These data reveal for the first time that the energetic cost of muscle activation is invariant with muscle length. In a separate experiment, we measure the total heat production of a muscle as it transitions into chemically-induced contracture.