The Effects of Chlorpromazine on the Electrical and Mechanical Activities of the Isolated Guinea Pig Heart

(1) The effects of chlorpromazine (CP) on the action potentials (AP's) and contractions of the isolated guinea pig heart were investigated by means of a microelectrode and a strain gauge transducer.(2) CP at concentrations of 2×10-6 to 5×10-1Gm./ml. decreased markedly the pacemaker activity of the sino-atrial node. By the repeated application of the drug to the tissue, however, a considerable tolerance to the drug was developed, and in some preparations the acceleration of the beat rate occurred rather than the deceleration.(3) CP shortened AP-duration of the left atrial muscle and the left ventricular papillary muscle by 10 to 20%, but slight prolongation occurred for a longer treatment with the drug in some preparations.(4) CP definitely decreased the maximum rate of rise of AP's of both atrial and ventricular muscles without significant change in the resting potential.(5) The excitability assumed by the strength-duration curve of the atrium was decreased by the application of CP, and the full-recovery time of the atrium was delayed.(6) Contractile tension of both the atrium and the ventricle was strikingly reduced by the application of CP, but recovery was almost complete.(7) Clinical electrocardiographic abnormalities induced by fairly high dosage of the phenothiazine drugs and antiarrhythmic actions of these drugs were discussed in relation to the results obtained.