Functional and metabolic effects of mexiletine in the rat heart-lung preparation

The effects of mexiletine on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. Mexiletine 1, 2, 4 or 8 micrograms ml-1 was administered 5 min after the start of perfusion. Heart rate decreased in the 2, 4 and 8 micrograms ml-1 groups significantly following the drug administration. The highest dose of mexiletine reduced cardiac output significantly, and this dose was associated with a higher incidence of dysrhythmias than the other groups. Although there was no significant difference in myocardial glycogen concentration among groups, ATP contents in the 4 micrograms ml-1 and 8 micrograms ml-1 groups were significantly less than in the control group. Lactate contents in the 4 micrograms ml-1 and 8 micrograms ml-1 groups were significantly higher than in the control group. Generally, the therapeutic plasma concentration of mexiletine is 0.5-2.0 micrograms ml-1. These results suggest that mexiletine may have a lesser margin of safety than lignocaine.