PubMed1975
In an attempt to develop an experimental model of pulmonary hypertension, five mongrel dogs were treated with 1 mg/kg p. o. and five with 1.5 mg/kg p. o. of Aminorex base five days a week for two years. A control group was given empty capsules by months. The following effects of treatment with Aminorex were noted: 1. Anorexia and central stimulation, 2. Natriuresis, 3. an increase in respiration rate, heart rate and body temperature, 4. a tendency towards usually compensated metabolic acidosis, 5. an increase in pulmonary arterial pressure, total pulmonary resistance and right ventricular work, and, in the group given the higher dose, a slight increase in mean aortic pressure and peripheral resistance. 6. Only slight histopathological changes were detectable, e.g.: perivascular oedema; increase in the number of muscle arteries, occasionally with hypertrophy of the tunica media and slight, focal fibro-elastoid thickening of the intima in some elastic arteries. These changes were present in about 60% of the treated dogs. Only one dog that died after 91 weeks' treatment also showed moderate, focal phlebosclerosis of large pulmonary veins and focal, fibro-elastoid thickening in the coronary artery. Serious morphological changes in the pulmonary vessels such as are observed in the human pulmonary hypertension were not seen in our laboratory animals. Two dogs in each dosage group died in the course of the experiment. The results of this experiment show that it is, in general, possible to induce pulmonary hypertension by administering Aminorex orally. In two dogs, however, pressure in the pulmonary artery (measured under anaesthesia) was below 20 mm Hg (controls: 13.8 +/- 1.3 mm Hg). One possible pathogenetic mechanism underlying the pulmonary hypertension would appear to be precapillary vasoconstriction induced by Aminorex, which can lead to transient, persistent or, for some unknown reason, even permanent fixation of pulmonary resistance.