Phentolamine for Vasodilator Treatment of Severe Heart-Failure

Majid, P A; Sharma, B; Taylor, Stanley H.

doi:10.1016/s0140-6736(71)92098-8

Cited by 268 publications

(40 citation statements)

References 24 publications

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“…There was a gradual return to pretreatment Discussion Therapy for heart failure consisting of reducing the afterload with vasodilator drugs has recently been advocated either as an alternative or adjunct to the traditional approach of using diuretics and inotropic agents.9 It has been shown that diuretics which reduce ventricular filling pressure may in fact decrease the cardiac output.10 Inotropic drugs which increase the velocity of fiber shortening and the systolic arterial pressure will augment the oxygen demands of the myocardium," whereas drugs which reduce the impedance to left ventricular outflow may increase the cardiac output and relieve the left ventricular wall tension. A variety of parenteral and oral vasodilator agents have been studied, including sodium nitroprusside," phentolamine, 13 nitroglycerin, 14 hydralazine," and prazosin. 6 Their effects vary'7 in terms of duration of action, degree of dilatation of the venous or arterial vessels, sympathetic stimulation, and influence on regional blood flows, particularly coronary flow.…”

Section: Resultsmentioning

confidence: 99%

Angiotensin converting enzyme inhibition in patients with congestive heart failure.

Gavras¹,

Faxon²,

Berkoben³

et al. 1978

Circulation

211

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The etiology of afterload elevation in congestive cardiac failure is unclear, but experimental evidence suggests a role for the renin-angiotensin system in maintaining elevated peripheral vascular resistance. The angiotensin converting enzyme inhibitor SQ20,881 was administered to eight patients with congestive cardiac failure (four hypertensives, four normotensives) during or one day after diagnostic cardiac catheterization. Various hemodynamic measurements performed before and during blockade indicate that this agent caused improvement in cardiac function in all patients by decreasing afterload. This improvement correlated with the decrease in total vascular resistance but was independent of the baseline blood pressure and plasma renin activity. These results suggest that inhibition of angiotensin converting enzyme is a worthwhile approach to the treatment of congestive heart failure, although its exact mechanism of action remains unclear.

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Section: Resultsmentioning

confidence: 99%

Angiotensin converting enzyme inhibition in patients with congestive heart failure.

Gavras¹,

Faxon²,

Berkoben³

et al. 1978

Circulation

211

View full text Add to dashboard Cite

show abstract

“…The reflex positive inotropic mechanism is probably also responsible for the lack of modification in dP/dT/LVEDP ratio. (Helfant, 1971;Harrison, 1978 (Franciosa, 1972;Majid, 1971;Gold, 1972). This therapeutic intervention should serve to emphasize the fact that cardiac performance and myocardial oxygen consumption are not always directly linked.…”

Section: Discussionmentioning

confidence: 99%

Effects of combined alpha‐ and beta‐blockade by labetalol in patients with coronary artery disease.

Condorelli¹,

Brevetti²,

Chiariello³

et al. 1982

Brit J Clinical Pharma

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1 The effect of labetalol 100 mg orally twice daily on exercise tolerance has been compared with placebo in 19 normotensive subjects with angiographic evidence of coronary artery disease. 2 Labetalol, at the same work load as during placebo exercise, significantly reduced systolic and diastolic blood pressures, as well as heart rate and rate-pressure product. 3 Similarly, ST segment depression was reduced by labetalol from 2.0 ± 0.4 to 1.36 ± 0.6 mm (P<0.001), thus enabling an increase in exercise tolerance from a control value of 83.7 ± 18 to 95.3 ± 19 W (P<0.005). 4 In seven other patients, also with coronary artery disease, the haemodynamic effects of a single 0.6 mg/kg intravenous dose of the drug was evaluated during exercise. 5 Compared with conditions during control exercise, labetalol induced a significant reduction in rate-pressure product from 17228 ± 2375 to 13445 ± 2404 mmHg/min (P<0.005) and in peripheral vascular resistance from 612.0 ± 61.2 to 512.7 ± 36.2 dyn cm-5 m-2 (P<0.0025). These events were not accompanied by any change in cardiac index and in dP/dT left ventricular end-diastolic pressure (LVEDP) ratio. 6 These data suggest that labetalol may induce reduction in myocardial oxygen consumption, thereby increasing exercise tolerance in patients with coronary artery disease, without impairment of left ventricular performance.

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“…Hematologic and biochemical measurements made 24 hours after drug infusion were not different from those before drug administration. Discussion Hemodynamic benefit from afterload reduction in patients with congestive heart failure was first demonstrated by Majid et al 23 Since then, an improvement in cardiac output after administration of a variety of agents with widely diverse pharmacologic actions but that all reduce SVR has suggested the important role of excessive vasoconstriction in perpetuating low cardiac output in these patients. 24 In addition, greater impairment of blood flow to the kidney than to other regional vascular beds25 tends to increase the demands on the already compromised myocardium because the extracellular fluid volume expands due to impaired salt and water excretion by the kidney.…”

Section: Hemodynamic Measurementsmentioning

confidence: 94%

Propylbutyldopamine: hemodynamic effects in conscious dogs, normal human volunteers and patients with heart failure.

et al. 1983

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SUMMARY The cardiovascular actions of a dopamine analog, propylbutyldopamine (PBDA), were examined for the first time in conscious dogs, normal human volunteers, and patients with congestive heart failure. PBDA lowered blood pressure without reflex increases in heart rate, increased renal blood flow, and decreased renal vascular resistance in dogs previously instrumented to allow measurement of arterial pressure and regional vascular flows in the conscious, unrestrained state. Pretreatment of the dogs with (S)-sulpiride, an antagonist selective for the dopamine receptor located on noradrenergic neurons (DA2), attenuated the reduction in arterial pressure but not the increase in renal blood flow produced by PBDA at a dose of 20 ,uglkg/min. The emetic potency of this dopamine analog also was examined in conscious dogs; the drug caused vomiting on two of 22 occasions at an i.v. infusion rate of 20 ,ug/kg/min and on six of 11 occasions at a dosage of 40 gg/kg/min. In contrast to its effects in conscious dogs, PBDA in nonemetic dosages uglkg/min) failed to lower blood pressure in three normal volunteers but slightly increased heart rate and doubled renal blood flow as measured by changes in the clearance of p-aminohippurate. Pretreatment of the volunteers with metoclopramide, 20 mg i.v., antagonized the increase in both heart rate and renal blood flow produced by PBDA. In 11 patients with congestive heart failure not due to valvular or congenital heart disease, i.v. infusion of PBDA at 5, 10 and 20 yg/kg/min resulted in dose-dependent reductions in mean arterial pressure, left ventricular filling pressure and pulmonary and systemic vascular resistances, and increases in cardiac index, without changes in either stroke work index or heart rate. The demonstration that PBDA decreases systemic vascular resistance and blood pressure in patients with heart failure and increases renal blood flow in dogs and normal volunteers introduces a new class of drugs with unique mechanisms of action and advantages for the treatment of conditions such as congestive heart failure and hypertension. The possibility that this drug class acts through activation of peripheral DA2 presynaptic and DA, postsynaptic dopamine receptors appears strong and further studies with this and similar agonists should stimulate the study of DA2 receptors in man.MANY therapeutic advances have occurred through development of drugs selective for specific adrenergic, histaminergic or cholinergic receptors. These achievements have stimulated the current interest in identifying specific dopaminergic receptors that might be involved in the pathogenesis of a variety of cardiovascular diseases or useful in their treatment. ' An ideal dopaminergic agonist should possess both presynaptic (DA2) adrenergic inhibitory activity and postsynaptic (DA1) vascular dilating activity in the renal bed without having cardiac chronotropic (/3w) or vascular constrictor (a,) effects. The last two actions limit the use of dopamine itself in the treatment of heart failure and hyperte...

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Phentolamine for Vasodilator Treatment of Severe Heart-Failure

Cited by 268 publications

References 24 publications

Angiotensin converting enzyme inhibition in patients with congestive heart failure.

Angiotensin converting enzyme inhibition in patients with congestive heart failure.

Effects of combined alpha‐ and beta‐blockade by labetalol in patients with coronary artery disease.

Propylbutyldopamine: hemodynamic effects in conscious dogs, normal human volunteers and patients with heart failure.

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