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Imidazoline as a hypotensive agent
American Federation for Clinical Research that its effect on the course of the hypertensive vascular disease can be ascertained. IMIDAZOLINEAS A HYPOTENSIVEAGENT. Coleman
D. Caplo&,
M.D.
and John H. Moyer, M.D.
(From the Baylor University College of Medicine, Houston, Tex.) Imidazoline (the hydrochloride salt of 2(N, p-tolyl-N-(m’oxy-phenyl)-amino-methyl)imidazoline) was investigated as a potential hypotensive agent in sixteen hypertensives. In all patients the intravenous or intramuscular administration of 1 or 2 mg. per kg. of the drug resulted in significant fall in blood pressure and moderate to severe postural hypotension. The mean fall in systolic pressures in the supine position was 38 mm. of mercury and in diastolic pressures 35 mm., occurring in approximately fifteen minutes. In the erect position, mean systolic fall was 89 mm. and mean diastolic fall 60 mm. The duration of response varied from forty minutes to several days. Side reactions occurred in fourteen patients and consisted of tachycardia, palpitation, a hot flushed feeling, cough, dyspnea, stuffiness of the nose, diaphoresis, nausea, weakness, dizziness and somnolence. Imidazoline was administered orally in doses of 30 to 120 mg. three to five times a day to eleven of the sixteen patients. Of these, five patients demonstrated slight to moderate postural hypotension and two had a drop in their reclining pressures. Three patients developed gastrointestinal symptoms (cramps and diarrhea, nausea and vomiting) necessitating cessation of oral therapy, and three others developed similar but milder symptoms. Five patients had no gastrointestinal side effects. From preliminary study it would seem that side effects will tend to limit the use of imidazoline to the severe hypertensive crises. RESPONSEOF PATIENTSWITH CONGESTIVEHEART FAILURE TO ACUTE ELEVATION OF TEMPERATURE AND HUMIDITY. G. S. Berenson, M.D. (From the Department of Medicine, Tulane University School of Medicine and Charity Hospital of Louisiana at New Orleans, La.) Observations were made to investigate the intolerance of patients with cardiac disease and congestive heart failure to stress of a hot and humid environment. Thirteen patients in various stages of congestive failure were studied and compared with thirteen control subjects. In three experiments one control subject and one patient with congestive failure were studied simultaneously. Following observations in comNOVEMBER,
1951
61 7
fortable atmospheric conditions, response to a hot and humid atmosphere (40 + 2”c., 85 per cent relative humidity) for periods of 40 to 114 minutes was noted. The heated surroundings precipitated acute attacks of “left ventricular failure” (cardiac asthma) characterized by severe dyspnea, orthopnea and pulmonary rales, associated with apprehension in five subjects with cardiac disease. Gallop rhythm developed or was accentuated in nine patients. Ability to withstand stress of a hot, humid environment was definitely less in subjects with congestive heart failure. This group exhibited primarily cardiovascular and pulmonary intolerance, whereas many central nervous system disturbances developed in the controls who were able to endure sufficiently prolonged exposures to the environment. The cardiovascular reactions’ in control subjects tended to be more uniform and were characterized especially by elevation of pulse pressure. These experiments indicate the intolerance of patients with certain types of cardiac disease to a hot and humid atmosphere and also suggest need for control of environmental atmosphere during therapy. EFFECTS OF PARITOL ON THE PROTHROMBIN TIMES,ANTI-THROMBINTIMES AND LEE-WHITE CLOTTING TIMES. Alan A. Ory, M.D. and Don W. Chapman, M.D. (From the Department of Medicine, Baylor University College of Medicine, Houston, Tex.) Of twenty-three dogs studied the following results were observed: (1) Paritol A in doses of 5 mg. per kg. of body weight was the most effective dose, giving a peak effect in fifteen to thirty minutes with Prolongation of the LeeWhite clotting time to twice or three times the normal value for four to five hours. (2) The prothrombin time, as measured by the LinkShapiro modification of Quick’s method may be notably prolonged by Paritol. (3) Protamine sulfate effects a prompt return of the clotting time to normal. Sixteen patients including three controls have been treated with Paritol C for twentyfour to seventy-two hours with an average of fifty hours without any demonstrable toxic effects or developments of clinical thrombosis or emboli. Patients initially received a dose of 5 mg. per kg. of Paritol C intravenously and 3 to 5 mg. per kg. when the clotting time fell helow twenty minutes. The clotting time was
D. Caplo&,
M.D.
and John H. Moyer, M.D.
(From the Baylor University College of Medicine, Houston, Tex.) Imidazoline (the hydrochloride salt of 2(N, p-tolyl-N-(m’oxy-phenyl)-amino-methyl)imidazoline) was investigated as a potential hypotensive agent in sixteen hypertensives. In all patients the intravenous or intramuscular administration of 1 or 2 mg. per kg. of the drug resulted in significant fall in blood pressure and moderate to severe postural hypotension. The mean fall in systolic pressures in the supine position was 38 mm. of mercury and in diastolic pressures 35 mm., occurring in approximately fifteen minutes. In the erect position, mean systolic fall was 89 mm. and mean diastolic fall 60 mm. The duration of response varied from forty minutes to several days. Side reactions occurred in fourteen patients and consisted of tachycardia, palpitation, a hot flushed feeling, cough, dyspnea, stuffiness of the nose, diaphoresis, nausea, weakness, dizziness and somnolence. Imidazoline was administered orally in doses of 30 to 120 mg. three to five times a day to eleven of the sixteen patients. Of these, five patients demonstrated slight to moderate postural hypotension and two had a drop in their reclining pressures. Three patients developed gastrointestinal symptoms (cramps and diarrhea, nausea and vomiting) necessitating cessation of oral therapy, and three others developed similar but milder symptoms. Five patients had no gastrointestinal side effects. From preliminary study it would seem that side effects will tend to limit the use of imidazoline to the severe hypertensive crises. RESPONSEOF PATIENTSWITH CONGESTIVEHEART FAILURE TO ACUTE ELEVATION OF TEMPERATURE AND HUMIDITY. G. S. Berenson, M.D. (From the Department of Medicine, Tulane University School of Medicine and Charity Hospital of Louisiana at New Orleans, La.) Observations were made to investigate the intolerance of patients with cardiac disease and congestive heart failure to stress of a hot and humid environment. Thirteen patients in various stages of congestive failure were studied and compared with thirteen control subjects. In three experiments one control subject and one patient with congestive failure were studied simultaneously. Following observations in comNOVEMBER,
1951
61 7
fortable atmospheric conditions, response to a hot and humid atmosphere (40 + 2”c., 85 per cent relative humidity) for periods of 40 to 114 minutes was noted. The heated surroundings precipitated acute attacks of “left ventricular failure” (cardiac asthma) characterized by severe dyspnea, orthopnea and pulmonary rales, associated with apprehension in five subjects with cardiac disease. Gallop rhythm developed or was accentuated in nine patients. Ability to withstand stress of a hot, humid environment was definitely less in subjects with congestive heart failure. This group exhibited primarily cardiovascular and pulmonary intolerance, whereas many central nervous system disturbances developed in the controls who were able to endure sufficiently prolonged exposures to the environment. The cardiovascular reactions’ in control subjects tended to be more uniform and were characterized especially by elevation of pulse pressure. These experiments indicate the intolerance of patients with certain types of cardiac disease to a hot and humid atmosphere and also suggest need for control of environmental atmosphere during therapy. EFFECTS OF PARITOL ON THE PROTHROMBIN TIMES,ANTI-THROMBINTIMES AND LEE-WHITE CLOTTING TIMES. Alan A. Ory, M.D. and Don W. Chapman, M.D. (From the Department of Medicine, Baylor University College of Medicine, Houston, Tex.) Of twenty-three dogs studied the following results were observed: (1) Paritol A in doses of 5 mg. per kg. of body weight was the most effective dose, giving a peak effect in fifteen to thirty minutes with Prolongation of the LeeWhite clotting time to twice or three times the normal value for four to five hours. (2) The prothrombin time, as measured by the LinkShapiro modification of Quick’s method may be notably prolonged by Paritol. (3) Protamine sulfate effects a prompt return of the clotting time to normal. Sixteen patients including three controls have been treated with Paritol C for twentyfour to seventy-two hours with an average of fifty hours without any demonstrable toxic effects or developments of clinical thrombosis or emboli. Patients initially received a dose of 5 mg. per kg. of Paritol C intravenously and 3 to 5 mg. per kg. when the clotting time fell helow twenty minutes. The clotting time was