Interaction of halothane and aminophylline on the isolated hemidiaphragm of the rat.

Halothane itself (1--3 vol percent) produced no significant changes in either Td or dT/dt max of the isolated hemidiaphragm during direct electrical stimulation. On the other hand, halothane significantly potentiated the effect of aminophylline on the resting tension of the muscle, both in a resting non-stimulated muscle and during direct electrical stimulation. Diethyl-ether did not affect the action of aminophylline on the resting tension. The interaction between halothane and aminophylline can be taken as a model for malignant hyperpyrexia. Procaine regularly produced further potentiation of the halothane-aminophylline interaction. There was no halothane-aminophylline interaction in a calcium-free medium. Verapamil was found to potentiate the halothane-aminophylline interaction, whereas di-Na-EDTA depressed it. Halothane did not significantly affect the actions of isoprenaline and adrenaline on Td and dT/dt max during direct electrical stimulation. So far, there is no obvious molecular basis for the action of halothane, but the available evidence indicates that its action is taking place both on the cell membrane and inside the cell, probably by blocking the reaccumulation of calcium in the sarcoplasmic reticulum and thus increasing the amount of free calcium in the cell.