Electrocardiographic changes induced by amrinone in the isolated perfused guinea-pig Langendorff heart preparation.

ECG changes induced by three different concentrations of amrinone were determined in the spontaneously beating guinea-pig Langendorff heart preparation. At a concentration of 50 micrograms/ml, there were no ECG changes except for a sinus tachycardia having a mean increase of 15.64 +/- 4.0, (P less than 0.01). At a concentration of 250 micrograms/ml, sinus tachycardia was more evident (+ 20.86% +/- 1.22; P less than 0.001). There was also a statistically significant shortening of the Q-T interval (P less than 0.001). With 1000 micrograms/ml, amrinone further increased heart rate (+ 45.10% +/- 13.26; P less than 0.001). There was a greater shortening of the Q-T interval, and occasionally sagging of the S-T segment. Dysrhythmic phenomena including coupled beats, at times with R waves appearing during the vulnerable period of the T wave; ventricular premature beats and alternating polymorphic ECG patterns, were evident. Second and third degree atrioventricular block preceded by marked prolongation of the P-R interval less commonly developed at this concentration. On the basis of these observations and others, it appears that as regards the development of cardiotoxocity, amrinone possesses a relatively wide margin of safety not less than 5 and may even approach 20.