The Effect of Khellin on Cardio-Pulmonary Function in Chronic Pulmonary Disease 12

Abstract

Extract from the fruit of the plant, Ammi Visnaga Lamn, has long been employed by inhabitants of the Middle East for relief of renal colic. The major biologically active component, khellin, was isolated in impure form by Fantl and Salem in 1930 (1). The chemical structure of khellin (visammin) was established by Spath and Gruber (2), and the pharmacology of this compound was investigated by several groups in Egypt, chief among them being Samaan (3) and Anrep, Barsoum, and Kenawy (4). These investigators have reported that khellin exhibits marked coronary dilator, bronchodilator and antispasmodic activity.Reports of beneficial results from its use in angina pectoris (5,6) and in bronchial asthma (7) prompted the Cardiovascular Department of this institution to investigate the effect of khellin in these diseases and in chronic cor pulmonale. The results of these studies have been previously reported elsewhere (8). In that study eight patients, clinically judged to have chronic cor pulmonale, were included. This group was characterized by pulmonary disease, diminished vital capacity, and in some instances, clubbing of the fingers and cyanosis. Four of the patients were in congestive heart failure. In all eight patients, khellin therapy resulted in improvement characterized by amelioration of dyspnea and wheezing, decreased cyanosis, increase in exercise capacity and an increased sense of well being.In order to delineate the mechanism responsible for the improvement noted in these patients, and to apply objective physiological criteria to such 1Aided in part by a grant from the National Heart studies, the present cardio-pulmonary investigation was undertaken. METHODThe patients in the present study consisted of six males with chronic pulmonary disease, not all of whom were as ill as those in the previous study (8). The patients were out-patients selected from the Mandel Clinic. Physical examination, fluoroscopy, chest films and electrocardiograms were taken shortly before the study. The electrocardiogram was normal in one patient and abnormal in five, but none showed evidence of right heart strain. The hemoglobin content of the blood ranged from 13.7 to 20.8 gm.%o; the hematocrits, from 48 to 59. The clinical data are summarized in Table I. All therapy was stopped for four to seven days before the study.The general plan of the study was to determine the effect of khellin on certain aspects of the respiratory and circulatory dynamics. The technique of right heart catheterization was combined with the simultaneous determination of respiratory gases in the arterial blood and in expired air, at rest and during exercise. Studies were made immediately before and after an intramuscular dose of the drug and were repeated after five to eight days of daily oral administration.Preliminary respiratory studies, consisting of maximum breathing capacity, vital capacity, inspiratory capacity and expiratory reserve volume (9) were determined at the beginning of the study. For this purpose a 9 liter Benedict-Roth spirometer was used...

The Effect of Acetylcholine on the Human Pulmonary Circulation Under Normal and Hypoxic Conditions1

“…Whether the small vessels of the lungs exercise similar control over the pressure in the pulmonary artery is not so certain. This uncertainty has stemmed largely from the fact that the human pulmonary vessels have exhibited an erratic response to many vasoactive drugs (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). As a consequence, most physiologists have concluded either that the pulmonary vessels are incapable of intrinsic changes in tone, or that the effect of such changes, if they occur, is less important in determining the pulmonary arterial pressure than is the effect of mechanical factors alone.…”