The Effects of Hexamethonium on Certain Manifestations of Congestive Heart Failure

Kelley, Robert T.; Freis, Edward D.; Higgins, Thomas F.

doi:10.1161/01.cir.7.2.169

Cited by 54 publications

(9 citation statements)

References 6 publications

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“…However, the reason for the opposite effects of ouabain on the forearm vascular resistance and venous tone of the two groups of patients studied has not yet been completely elucidated.. Some investigators have postulated that the peripheral vasoconstriction in patients with congestive heart failure results from increased activity of the sympathetic nervous system (29), a view supported by the finding that the vasoconstriction has been diminished by ganglionic blockade (30,31). The elevation of cardiac output induced by ouabain in patients with heart failure may result in a diminution of the adrenergically induced arteriolar and venoconstriction in the forearm.…”

Section: Discussionmentioning

confidence: 99%

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Mason¹,

Braunwald²,

Karsh³

et al. 1964

J. Clin. Invest.

304

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Although the therapeutic action of digitalis is generally agreed to result largely from its ability to stimulate the contraction of the myocardium, there has been considerable suspicion that cardiac glycosides may also act directly upon the systemic vascular bed. Excised arterial and venous strips contract when exposed to digitalis glycosides (1-4), and generalized systemic arteriolar and venous constriction has been induced by digitalis in-anesthetized open-chest dogs on cardiopulmonary bypass (5, 6). In normal human subjects digitalis glycosides elevate arterial pressure and either have little effect on or diminish cardiac output, thus augmenting the calculated systemic vascular resistance (7). More direct evidence that digitalis acts upon vascular smiiooth muscle was provided by the observation that the drug elevated systemic vascular resistance in patients on total cardiopulmonary bypass, in whom the systemic perfusion rate was held constant, and in whom the cardiac effects of the drug could not influence arterial pressure directly (8). Little information is available, however, concerning the extracardiac actions of digitalis glycosides when given in the usual clinical doses to intact human subjects. The present investigation was undertaken to characterize the effects of ouabain on a specific vascular bed, that of the forearm. The effects of the drug on both the resistance and capacitance vessels were examined in normal subjects and in patients with congestive heart failure. Materials and MethodsThe effects of ouabain were determined in 12 normal subjects, between 18 and 49 years of age, and in 6 patients with congestive heart failure, between 34 and 52 years in age. Four of these patients had rheumatic mitral

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Section: Discussionmentioning

confidence: 99%

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Mason¹,

Braunwald²,

Karsh³

et al. 1964

J. Clin. Invest.

304

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“…Hexamethonium by its blocking action on vasoconstrictor reflexes abolishes this increased tone thus permitting a decrease in total peripheral resistance and thereby also in the demand for cardiac work. These considerations and their implications in regard to the nature of congestive heart failure have been discussed more fully in another communication (20).…”

Section: Discussionmentioning

confidence: 99%

The Hemodynamic Effects of Hypotensive Drugs in Man. Iii. Hexamethonium 123

Freis¹,

Rose²,

Partenope³

et al. 1953

J. Clin. Invest.

Self Cite

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While searching for derivatives of d-tubocurarine, Barlow and Ing (1) and Paton and Zaimis (2) independently synthesized a series of polymethylene bistrimethylammonium salts. The latter investigators demonstrated that the pharmacological properties of this series were related to the length of the polymethylene chain; the decacompound produced neuromuscular block while the penta and hexa-compounds prevented the transmission of impulses across the synapses in all autonomic ganglia. They also carried out preliminary trials in man (3) but Arnold and Rosenheim were the first to use these agents in hypertension (4). Finally, Restall and Smirk demonstrated that it was possible to reduce blood pressure and obtain clinical improvement in hypertensive patients for long periods by the use of repeated parenteral doses of hexamethonium (5).Studies in this laboratory have confirmed the observations of Restall and Smirk and in addition have shown the potentiating effect of 1-hydrazinophthalazine (Apresoline) when alternated with doses of hexamethonium in patients with hypertension (6, 7). Our studies also suggested that hexamethonium may be useful in the treatment of

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“…Reprinted with permission from Circulation. 9 Copyright American Heart Association, 1953.© The average fall in BP from the aorta to these small arteries was as follows: from aorta to 1-mm-diameter arteries, 7.5 mm Hg systolic and 5.5 mm Hg diastolic; and from aorta to 200-m-diameter arteries, 17 mm Hg systolic and 12 mm Hg diastolic. Therefore, the resistance vessels, where the steepest drop in BP occurs, must be in arterioles Ͻ200 m in diameter.…”

Section: Hemodynamics Of Blood Vessels Blood Pressure In Very Small Amentioning

confidence: 99%

“…Hexamethonium was the most effective, not only as an antihypertensive agent but also as a pharmacological tool in hemodynamic research. 9,11 Thiazide Diuretics I was fortunate to be the first to announce the treatment of hypertension with chlorothiazide at the 1957 annual meeting of the American Heart Association. 26 We found that chlorothiazide enhanced the antihypertensive action of other drugs more effectively than any other drug.…”

Section: Studies In Hypertension Early Drug Treatments Of Hypertensionmentioning

confidence: 99%

Invited Review

2001

Hypertension

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Abstract-This review covers a representative sampling of investigations in hemodynamics and hypertension performed by the author during the period from approximately 1945 to 1980. The hemodynamic studies included a description of changes associated with congestive heart failure and with acute myocardial infarction. These studies emphasized for the first time the importance of left ventricular afterload and of the mobilizable venous reservoir. Other hemodynamic studies included diverse subjects such as the first and only recordings of pulse waves in arteries as small as 200 ␥m in diameter, velocity differences between red blood cells and plasma, turbulent blood flow in the ascending aorta, increase in velocity of blood flow of leg veins under compression, rates of transcapillary flow of solutes in humans, and the first use of external arterial pulse wave recordings to assess vascular compliance. Pioneer studies in hypertension included the first use of an antihypertensive drug to treat malignant hypertension and the first report of the treatment of hypertension with a thiazide diuretic. (Hypertension. 2001;38:1-5.)

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The Effects of Hexamethonium on Certain Manifestations of Congestive Heart Failure

Cited by 54 publications

References 6 publications

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

Studies on Digitalis. X. Effects of Ouabain on Forearm Vascular Resistance and Venous Tone in Normal Subjects and in Patients in Heart Failure *

The Hemodynamic Effects of Hypotensive Drugs in Man. Iii. Hexamethonium 123

Invited Review

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