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.
Kume
M
M
Department of Anaesthesiology, Yamanashi Medical College, Japan.
Kashimoto
S
S
Kumazawa
T
T
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006327:Heart Block / Q000517:prevention & control; D006339:Heart Rate / Q000187:drug effects; D007773:Lactates / Q000032:analysis; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000494:pharmacology*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY
D007773:Lactates; D008801:Mexiletine; D000255:Adenosine Triphosphate