{'fraction_non_alphanumeric': 0.036758563074352546, 'fraction_numerical': 0.05263157894736842, 'mean_word_length': 4.960199004975125, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Investigations of the cardiac actions of SK&F 86466 in the rabbit

The cardiac effects of SK&F 86466, an α2‐adrenoceptor antagonist currently under evaluation in humans as an antihypertensive agent, were investigated in rabbits. In the isolated working rabbit heart, SK&F 86466 had no effect on spontaneous heart rate, contractility, coronary flow, aortic flow, or left ventricular pressure at concentrations from 10−7 to 3 × 10−5 M. At higher concentrations, SK&F 86466 lowered heart rate, contractility, aortic flow, and left ventricular pressure to such an extent that the heart failed to perform work. Electrophysiologic studies of spontaneous actions potentials of sino‐atrial node cells revealed that from 10−9 to 10−5 M, SK&F 86466 had no effect on action potential generation. At 3X 10−5 M, a 25% decrease in the rate of spontaneous action potentials was observed. This effect was accompained by a 1.3 V/sec decrease in + Vmax and a 25% increase in APD50. These results suggest that: 1) SK&F 86466 has no direct cardiodepressant action in rabbits at pharmacologically relevent doses, and 2) the actions of SK&F 86466 on the heart are most likely due to an effect on inward calcium current.