Effect of tetraethylammonium in arterial hypertension

Dale in 1906 recognized the sympatholytic activity of crude extracts of ergot as well as their property of direct stimulation of smooth muscle, including that of the blood vessels (1). Despite their sympatholytic effects their direct vasoconstrictor action prevented significant lowering of arterial pressure.Later chemical purification of the crude drug resulted in the isolation of five alkaloids: ergotamine (2), ergobasine (3), ergokryptine, ergocornine and ergocristine (4). The basic chemical structure of these compounds was clarified by Jacobs and Craig (5) who demonstrated the presence of lysergic acid in all of the alkaloids (6). By hydrogenating the reducible double bond of the lysergic acid component of four of these alkaloids, Stoll and Hofmann (7) in 1943 produced a new series of compounds, dihydroergotamine, dihydroergocristine, dihydroergocornine (DHO-180) 5 and dihydroergokryptine (DHK-135).5 Pharmacological studies in animals (8) indicated that these modified compounds have enhanced sympatholytic and adrenolytic properties but little or no direct constrictor action on smooth muscle. In addition, they are hypotensive, this effect being mediated at least in part via the central nervous system (9). In man DHO and DHK in non-toxic doses have sympatholytic and hypotensive prop- erties (10-12). Because of their possible value in the treatment of essential hypertension and peripheral vascular disease a further clarification of their hemodynamic effects in man was undertaken. MATERIALS AND METHODSThe subjects were patients, mostly hypertensive, admitted to the wards of the Massachusetts Memorial Hospitals. The methods used in this investigation were essentially the same as those described in a previous communication (13). DHO was administered by intravenous injection in a solution of sterile water containing 0.5 mg. of active substance per cc. Unless otherwise indicated arterial pressure was measured continuously with a Hamilton manometer (13). RESULTS I. Sympatholytic Effects a. Sympathetic Vasopressor ResponsesCertain vasopressor responses usually abolished or diminished after surgical sympathectomy (14)

Section: Discussionmentioning

confidence: 99%

The Hemodynamic Effects of Hypotensive Drugs in Man. Ii. Dihydroergocornine 1

Freis¹,

Stanton²,

Litter³

et al. 1949

“…Hoobler and his associates (12) and others (9,10) have found that TEAC blockade is less complete than paravertebral block. Soloff, Burnett and Bello (13) failed to find any agreement between the vasodepressor action of TEAC and spinal anesthesia while Ferris and his co-workers (3) have demonstrated a close parallelism between the blocking action of both agents.…”

Section: Methodsmentioning

confidence: 98%

“…This question gained more strength in the face of the conflicting opinions regarding the extent of the blocking action of TEAC as compared to that of spinal anesthesia or paravertebral block (3,(9)(10)(11)(12)(13) …”

mentioning

confidence: 99%

Studies on Autonomic Blockade. I. Comparison Between the Effects of Tetraethylammonium Chloride (Teac) and High Selective Spinal Anesthesia on Blood Pressure of Normal and Toxemic Pregnancy 1

Assali¹,

Prystowsky²

1950

Previous studies have indicated that autonomic blockade with tetraethylammonium chloride produces different effects in normal term pregnancy and in toxemia of pregnancy (1-4). In the former, a fall in the blood pressure to very low levels occurs, while in the latter the blood pressure fall is negligible. This led to the belief that in normal pregnancy the blood pressure is maintained mainly by neurogenic impulses, while in toxemic pregnancy the blood pressure is supported principally by humoral mechanisms. It was also suggested that a certain degree of venous pooling might be a contributing factor in the blood pressure fall following autonomic blockade with TEAC.Since recent reports (5)(6)(7)(8) extensive blockade achieved with higher concentrations of anesthetic solutions. MATERIALThe material consisted of 12 normal term pregnancies; 15 toxemic pregnancies (two cases with convulsive eclampsia, 11 with severe pre-eclampsia and two cases with pre-eclampsia superimposed on pre-existing essential hypertension); and five healthy, young normotensive non-pregnant females (medical students and paid volunteers). A total of 32 patients submitted to 66 high spinal and 73 TEAC tests (some of the patients had more than one test with both spinal and TEAC). The age of the patients ranged from 15 to 40 years, an average of 24.5 years. The diagnosis of pre-eclampsia and eclampsia was based on the same criteria as outlined by Brust, Assali, and Ferris (1). Of the 12 normal pregnant females, 10 patients were studied in the prepartum and postpartum periods; two refused the postpartum test. Among the toxemic group, 12 were studied in the prepartum and postpartum periods; three refused the postpartum test.In all normal pregnant patients the prepartum tests were performed between 33 and 40 weeks' gestation. The postpartum assays were done 36 to 48 hours after delivery. Toxemic patients were studied prepartum at the height of toxemic symptoms; in the postpartum period the study was performed when all signs of toxemia had subsided (only one patient had her postpartum test while she was still toxic). METHODAll of the patients were on the ward, without any medication, for at least 24 hours prior to the test. None was in labor. Both TEAC and spinal anesthesia studies were conducted with the patient lying in the supine position on an operating table which was maintained always in the horizontal position. Tilting of the table to obtain changes in the anesthetic level was not done because the anesthetic solution used was practically isobaric and its simple diffusion and dispersion in the spinal fluids were sufficient to obtain the desired level. The blood pressure was recorded by a mercury sphygmomanometer attached to one arm and maintained at heart level. Pulse rate was recorded at either radial or carotid artery.1354

“…In four of five cases, the pattern became definitely abnormal after TEAC. TEAC is said to have a direct action upon the heart (14) in animals, increasing work capacity and reducing auricular pressures of the failing heart in the heart-lung preparation (13). Hoobler and his colleagues state, however, that no direct cardiac effect may be anticipated in the human subject (13).…”

Section: Complicationsmentioning

confidence: 99%

Observations on Autonomic Participation in Pulmonary Arteriolar Resistance in Man 1

Fowler¹,

Westcott²,

Hauenstein³

et al. 1950

It has been generally believed that the autonomic nervous system plays an insignificant role in the regulation of pressure within the pulmonary or lesser circulation. In 1939, Hamilton (1) studied the effect of various drugs upon the pulmonary arterial and venous pressures in unanesthetized dogs. He concluded that there was no evidence of autonomic control of the pulmonary circulation. Dirken and Heemstra (2), however, in 1948 found that resection of part of the sympathetic trunk increased pulmonary blood flow in rabbits. They found that vagotomy had no effect upon pulmonary flow.Without knowledge of the pulmonary venous or "capillary" pressure, one cannot ascertain whether changes in pulmonary arterial pressure are due primarily to a change in cardiac output or to a variation in pulmonary arteriolar resistance. Until recently, the study of autonomic regulation of pulmonary blood flow in man could not be undertaken because of the lack of a satisfactory method of measuring pulmonary venous pressure, except in an occasional case of atrial septal defect. In 1948, Hellems and co-workers (3) described a method for determining pulmonary "capillary" pressure and have since given adequate proof that this pressure varies with the pulmonary venous pressure (4). When the pulmonary artery pressure, pulmonary "capillary" pressure, and cardiac output are determined simultaneously, the pulmonary arteriolar resistance may be calculated (5).With the foregoing in mind, it was decided to determine the effect of the autonomic blocking agent, tetraethylammonium chloride (TEAC), upon the pulmonary arteriolar resistance in man; this report describes the results of such studies. MATERIALIt was thought that patients having pulmonary hypertension would be more likely to show a lowering of pulmonary pressure following autonomic blockade by tetraethylammonium because the effect of such blockade is much more pronounced in the systemic circulation when hypertension is present (6). A total of 15 patients were studied. Five were normal; two had pulmonary emphysema; two, congestive heart failure; one, active pneumonia; three, hypertensive vascular disease; one, bronchiectasis; one, diaphragmatic hernia with cor pulmonale. METHODThe majority of the patients were studied in the fasting condition. Cardiac catheterization was performed by the method of Cournand and Ranges (7). A double lumen catheter was used in order that pulmonary "capillary" pressure and pulmonary arterial pressure could be measured simultaneously. Pulmonary "capillary" pressure was obtained by the method of Hellems and his associates (3). The catheter was advanced into a branch of the pulmonary artery as far as possible, so that the branch was occluded and the pressure distal to the point of occlusion was obtained. Resting cardiac outputs were obtained usually after the catheter had been in place 15 to 30 minutes or more.