Studies on Digitalis. I. Direct Effects on Peripheral Vascular Resistance

Ross, John; Waldhausen, John A.; Braunwald, Eugene; Lewis, Robert M.

doi:10.1172/jci104113

Cited by 134 publications

(38 citation statements)

References 14 publications

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“…Detailed animal studies also show potent vasoconstrictor responses to digitalis administration in both skeletal and coronary vascular beds because of central neural or efferent sympathoexcitatory mechanisms.12-14 Direct vasoconstriction is also observed when these agents are applied to vascular smooth muscle. [15][16][17] In 1964, Mason and Braunwald18 reported that intravenous ouabain causes forearm arterial and venous vasoconstriction in normal subjects, whereas vasodilation is exhibited by patients with heart failure. Prior studies in our laboratory confirmed this vasodilatory response after intravenous administration of rapidly acting digitalis preparations in patients with heart failure and suggested that these agents also quickly normalize baroreflex circulatory control mechanisms.…”

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confidence: 99%

Sympathoinhibitory responses to digitalis glycosides in heart failure patients. Direct evidence from sympathetic neural recordings.

et al. 1989

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Digitalis glycosides exert both excitatory and inhibitory autonomic actions in animals and produce vasoconstriction in normal humans but produce vasodilation in heart failure patients.To determine whether or not these contrasting vascular responses are due to differing autonomic actions of the drug, we compared the responses to intravenous administration of Cedilanid-D (0.02 mg/kg) in eight normal subjects (mean age, 23+±1 years) and eight patients with moderate-to-severe heart failure (mean age, 52±5 years, NYHA Class III-IV). Hemodynamics and efferent sympathetic nerve activity to muscle (MSNA) were measured during 5-minute periods before (control) and 20 minutes after drug administration. In the heart failure patients, Cedilanid-D significantly increased systolic and pulse pressures, whereas mean arterial pressure was unchanged. There was a decrease in right atrial pressure and a tendency for a decrease in pulmonary artery diastolic pressure with a slowing of heart rate. Cardiac index increased by 24±-7%. Short-term administration of digitalis in these heart failure patients produced a fall in forearm vascular resistance (from 37.6±8.2 to 31.8± 8.1 units, p <0.05) and an early, profound, and sustained decrease in MSNA (from 831.0±118.4 to 474.4+103.6 units/ 100 heart beats, p <0.01). Digitalis glycosides produced different vascular and MSNA responses in the normal subjects. In the normal volunteers, the drug significantly increased systolic, mean, and pulse pressures and decreased central venous pressure and heart rate. Despite the significant increase in arterial pressure, there was no change in forearm vascular resistance (from 11.7+ 1.0 to 12.7+ 1.0 units, p=NS) or MSNA (from 494.8±88.5 to 369.1± 60.5 units/100 heart beats, p=NS), suggesting a sympathoexcitatory response in normal subjects. To determine whether or not the digitalis-induced sympathoinhibition in the heart failure patients was simply due to an inotropic effect (stimulation of inhibitory cardiac mechanoreceptors), we studied the responses of seven additional patients with heart failure before and during administration of dobutamine (3.4±+0.4 ,ug/kg/min). Dobutamine produced a 34±3% increase in cardiac index, no significant change in systemic arterial pressures, a decrease in pulmonary artery diastolic and right atrial pressures, and no change in heart rate or forearm vascular resistance (from 30.2 ±4.3 to 26.5 ±4.7 units, p=NS). In contrast to the sympathoinhibition seen after digitalis administration and despite comparable inotropic effects of the two agents, there was no change in MSNA during dobutamine infusion (from 527.6±112.7 to 443.7+ 95.9 units/ 100 heart beats, p=NS). These studies provide the first direct evidence that digitalis glycosides produce marked sympathoinhibitory actions in humans with heart failure, an efect that likely cannot be ascribed solely to an inotropic action of the drug. We suggest these autonomic effects result from afferent activation of low-or high-pressure baroreceptor mechanisms by digitalis in patients wit...

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confidence: 99%

Sympathoinhibitory responses to digitalis glycosides in heart failure patients. Direct evidence from sympathetic neural recordings.

et al. 1989

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“…In other reports, a strong pressor effect of digitalis both in the dog (17), and in patients (12) undergoing cardiopulmonary bypass was reported. The present experiments indicate that digitalis glycosides also have a venoconstrictor action in the dog.…”

Section: Resultsmentioning

confidence: 74%

“…In one experiment, 0.5 cat unit per kg lanatoside C was administered. In the dogs receiving acetylstrophanthidin, the alterations in blood volume presented are those existing at the time the blood pressure elevation resulting from digitalization had returned to the control level (17). In the dog receiving lanatoside C the pressor response persisted and the volume change presented is that which existed at the time when both arterial pressure and blood volume had stabilized.…”

Section: Methodsmentioning

confidence: 99%

“…Anesthesia was administered with morphine, chloralose and urethan; complete bypass of the heart and lungs was established, and pressure and flow measurements carried out as previously described (17). Perfusion rates were kept constant throughout each experiment and varied from 83 to 108, averaging 97 ml drains by gravity from the superior vena cava (SVC) and inferior vena cava (IVC) to the oxygenator.…”

Section: Methodsmentioning

confidence: 99%

“…Tainter and Dock (16) observed an increase in portal venous pressure following digitalis administration in the dog and postulated that hepatic vein constriction resulted in pooling of blood in the splanchnic bed. It is now clear that digitalis glycosides act directly on the peripheral circulation of both dog and man (12,17). To define further the peripheral actions of these drugs, a preparation was developed which permitted characterization of the effects of digitalis on the capacity of the peripheral vascular bed and on venous return.…”

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confidence: 99%

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