Kathleen E. Needham

Efficacy of oral angiotensin-converting enzyme inhibition with captopril therapy in severe chronic normotensive congestive heart failure

To evaluate the therapeutic efficacy of oral angiotensin-converting inhibition (ACE) with captopril in chronic normotensive congestive heart failure (CHF), acute and cardiocirculatory actions were determined by cardiac catheterization and forearm plethysmography, and ambulatory effects were assessed by echocardiography, nuclear angiography, treadmill exercise, and clinical symptomatology in 10 severe CHF patients. Captopril (90 mg) produced marked (peak 1 hour) and sustained (5 hours) left ventricular filling pressure (23 to 15 mm Hg), systemic vascular resistance decreases, and cardiac index increase (1.99 to 2.41 L/min/m2), while mean blood pressure declined mildly (87 to 80 mm Hg) without heart rate change. Both forearm venous tone and vascular resistance decreased considerably. After 1 week of ambulatory therapy (90 mg three times daily), nuclear angiographic ejection and echocardiogram shortening fractions increased, and exercise duration (341 to 453 sec) and New York Heart Association functional class (3.6 to 2.2) improved. Thus ACE-induced vasodilation by oral captopril improved cardiac performance and clinical status in refractory CHF.

Hemodynamic effects of oral pirbuterol in chronic severe congestive heart failure.

SUMMARY The achievement of satisfactory ambulatory therapy of severe chronic congestive heart failure may be helped by the development of safe and orally effective cardiotonic agents. Therefore, we evaluated by cardiac catheterization and limb plethysmography the temporal cardiocirculatory responses of the new ingestible β agonist pirbuterol in 10 coronary heart disease patients with severe congestive heart failure refractory to digitalis and diuretics. After a single oral dose of 0.4 mg/kg, ventricular dysfunction was considerably improved during 6 hours of hemodynamic monitoring. Cardiac index increased from a control of 1.7 I/min/m2 to 2.6 I/min/m2 (p < 0.001) at 1 hour and to 2.4 1/min/m2 (p < 0.005) at 3 hours and was 2.2 1/min/m2 (p < 0.001) at 6 hours; left ventricular filling pressure decreased from a control of 24 mm Hg to 19 mm Hg (p < 0.005) at 1 hour and to 18 mm Hg (p < 0.005) at 3 hours and was 22 mm Hg (p < 0.05) at 6 hours. Concomitantly, the peak increment in heart rate (6 beats/min) was minimal and without ectopy and mean arterial blood pressure decreased only 10 mm Hg. Total systemic vascular resistance declined by 887 dyn-sec-cm−5, forearm venodilation occurred and the rate-pressure product was unaltered. Thus, oral pirbuterol provides beneficial hemodynamic effects in patients with severe left ventricular dysfunction and appears potentially useful for long-term management of low-output congestive heart failure.

Long-term hemodynamic and clinical efficacy of captopril therapy in ambulatory management of severe chronic congestive heart failure

The 6-month extended vasodilator efficacy of the oral angiotensin converting enzyme (ACE) inhibitor, captopril (CPT), was evaluated by sequential cardiac catheterization, nuclear scintigraphy, echocardiography, treadmill exercise, and symptomatology in nine patients with severe chronic left ventricular (LV) failure (CHF). CPT lowered LV filling pressure (from 23 to 14 mm Hg acutely (p less than 0.001) and to 14 mm Hg (p less than 0.01) with continuous 6-month therapy; concomitantly CPT raised cardiac index from 2.03 to 2.46 L/min/m2 initially (p less than 0.02) and to 2.33 L/min/m2 (p less than 0.02) at 6 months. Simultaneously CPT raised LV ejection fraction from 0.21 to 0.25 acutely (p less than 0.01) and to 0.30 (p less than 0.001) and to 60 mm (p less than 0.001) at 6 months. These beneficial actions of CPT on LV pump function raised treadmill exercise duration (from 339 to 426 seconds initially (p less than 0.05) and to 499 seconds (p less than 0.05) at 6 months, while considerably reducing CHF symptomatology (p less than 0.001). Thus ACE inhibition by CPT provides markedly beneficial sustained hemodynamic and clinical improvement in advanced LV failure without fluid accumulation or late vasodilator drug tolerance.

Hemodynamic actions of prenalterol in severe congestive heart failure due to chronic coronary disease

To provide improved inotropic agents for enhanced therapy of severe congestive heart failure (CHF), the hemodynamic efficacy of prenalterol (PN), a recently developed cardioselective beta-1 receptor agonist, was evaluated by cardiac catheterization in nine patients with refractory CHF due to chronic coronary disease. PN (4.8 mg intravenously) markedly augmented the cardiac index from 1.9 to 2.6 L/min/m2 (p less than 0.01) and substantially elevated stroke index from 24 to 30 ml/beat/m2 (p less than 0.001). Additionally, PN raised stroke work index 21 to 26 gm.m/m2 (p less than 0.005) and decreased total systemic vascular resistance from 1,702 to 1,260 dynes-sec cm(-5) (p less than 0.001). Concomitantly, heart rate, mean blood pressure, and left ventricular filling pressure were unaltered ( p greater than 0.05). Importantly, the heart rate-systolic blood pressure product was unchanged (p less than 0.05), and precipitation of cardiac dysrhythmias or myocardial ischemia was not observed. Thus PN produced considerable improvement of depressed cardiocirculatory performance without untoward effects and thereby appears a valuable new cardiotonic in the clinical management of severe low output ventricular dysfunction.

Cardiocirculatory and myocardial energetic effects of prostaglandin E1 in severe left ventricular failure due to chronic coronary heart disease.

The cardiocirculatory actions of brief (69 +/- 5 minutes) infusions of prostaglandin E1 were evaluated in nine chronic coronary heart disease patients with severe left ventricular (LV) failure caused by previous myocardial infarction. Prostaglandin E1 infusion did not alter heart rate (HR) and produced modest declines in mean systemic blood pressure (BP) (85 +/- 6 to 76 +/- 5 mm Hg, P less than 0.025) and LV filling pressure (19 +/- 3 to 15 +/- 2 mm Hg, P less than 0.01). Simultaneously, prostaglandin E1 augmented LV pump function raising cardiac index from 1.9 +/- 0.2 to 2.5 +/- 0.1 L/min/m2 (p less than 0.005), elevating stroke index from 28 +/- 2.4 to 35 +/- 2.9 ml/beat/m2 (p less than 0.01), and increasing stroke work index from 26 +/- 4.3 to 30 +/- 4.4 gm . m/m2 (p less than 0.02). Additionally, total systemic vascular resistance decreased from 1862 +/- 192 to 1282 +/- 100 dynes-sec-cm-5 (p less than 0.02) and double product LV aerobic index of HR . systolic BP diminished from 9492 +/- 666 to 8278 +/- 492 (p less than 0.02). Concomitantly, in the forearm, vascular resistance fell, blood flow rose, and venous tone remained unchanged. These results indicate that prostaglandin E1 is a potent systemic arteriolar dilator with markedly beneficial effects on cardiac function in chronic coronary patients having severe ischemic LV failure refractory to conventional therapy.

Therapeutic efficacy of oral pirbuterol in severe chronic congestive heart failure: Acute hemodynamic and long-term ambulatory evaluation

Abstract Development of effective orally administered cardiotonic agents for sustained ambulatory therapy of severe chronic congestive heart failure (CHF) is currently of considerable clinical interest. Thus we evaluated temporal cardiocirculatory responses to the new ingestible beta-adrenergic receptor agonist pirbuterol (PBL) (0.4 mg/kg) by cardiac catheterization and limb plethysmography in 10 patients with coronary disease and severe CHF refractory to digitalis and diuretics. PBL considerably improved left ventricular (LV) dysfunction during the 6-hour period of hemodynamic monitoring: control lowered cardiac index (CI) of 1.7 L/min/m 2 rose to 2.6 (p 2 (p 2 (p 2 (p 2 (p 0.05) MAP and LVFP, PBL modestly diminished MAP from 83 to 75 mm Hg (p −5 (p −5 (p

Therapeutic application of prazosin in chronic refractory congestive heart failure: Tolerance and “tachyphylaxis” in perspective☆

The cardiocirculatory actions on the oral vasodilator prazosin were evaluated by cardiac catheterization, forearm plethysmography, echocardiography, treadmill exercise and symptoms in patients with advanced long-standing congestive heart failure. The administration of oral prazosin (2 to 7 mg) reduced forearm venous tone and forearm vascular resistance. Concomitantly, mean systemic arterial pressure and left ventricular filling pressure decreased, and the cardiac index increased. These effects of a single dose of prazosin on left ventricular function were rapid in onset, maximal at 1 hour and sustained for the entire 6-hour period of observation. After two weeks of outpatient therapy with 2 to 7 mg of prazosin four times daily, echographic end-diastolic dimension decreased, whereas the duration of treadmill exercise increased. Symptoms (dyspnea, fatigue, angina) were diminished throughout the course of prazosin therapy, and there was an improvement in the New York Heart Association functional class from 3.7 to 2.2. Thus, prazosin possesses sustained nitroprusside-like balanced dilator actions of the systemic arterial and venous beds, which are effectively translated into the beneficial hemodynamic effects of augmenting cardiac output and relieving excessive left ventricular end-diastolic pressure. The delayed vasodilator tolerance that occurs in 30 percent of the patients is prevented by the prior use of aldosterone antagonists and is easily treated when present. Subacute hemodynamic suppression of beneficial prazosin vasodilator actions is transient and does not preclude successful sustained prazosin therapy of severe heart failure.

Comparison of Hemodynamic Actions of Pirbuterol and Dobutamine on Cardiac Function in Severe Congestive Heart Failure

Abstract There is considerable interest in the development of beneficial oral inotropic agents for sustained ambulatory management of patients with severe chronic congestive heart failure. Therefore, the hemodynamic actions of the oral beta adrenergic receptor agonist pirbuterol and of intravenous dobutamine were compared in nine patients with severe heart failure. Both agents produced similar effects on ventricular pump function: The cardiac index was markedly increased from 1.8 to 2.6 liters/min per m 2 (p 2 (p 2 (p 2 (p 2 (p 2 (p −5 (p −5 . Neither agent altered heart rate or the heart rate-systolic blood pressure product (p Thus, oral pirbuterol has dobutamine-like beneficial hemodynamic effects on left ventricular pump function but causes a greater decrease in total systemic vascular resistance consistent with the combined inotropic and peripheral vasodilator actions of this oral beta adrenergic receptor agonist. These salutary hemodynamic responses suggest that oral pirbuterol may be useful for the prolonged treatment of severe chronic congestive heart failure.

Management of refractory congestive heart failure with prazosin

The cardiocirculatory actions of prazosin (PZN) orally were evaluated by cardiac catheterization, forearm plethysmography, echocardiography, treadmill exercise, and symptoms in patients with advanced long-standing congestive heart failure (CHF). PZN orally (2 to 7 mg) reduced forearm venous tone and decreased forearm vascular resistance. Concomitantly mean systemic arterial pressure declined, left ventricular filling pressure (LVFP) decreased, and cardiac index (CI) was raised. These effects of a single dose of PZN on LV function were rapid in onset, maximal at 1 hour, and sustained for the entire 6 hours of observation. After 2 weeks of outpatient therapy with 2 to 7 mg PZN four times daily, echographic LV end-diastolic dimension decreased and the duration of treadmill exercise increased. Symptoms (dyspnea, fatigue, angina) were diminished throughout the course of PZN therapy, and New York Heart Association functional class improved for III to II. Thus PZN possesses sustained nitroprusside-like balanced dilator actions on the systemic arterial and venous beds, which are effectively translated into beneficial hemodynamics of augmenting lowered cardiac output and relieving excessive LVFP. Delayed vasodilator tolerance, occurring in 30% of patients, is prevented by prior use of aldosterone antagonists and is easily treated. Subacute hemodynamic suppression of beneficial PZN vasodilator actions is transient and does not preclude successful sustained PZN therapy of severe chronic CHF.

Effect of combined nitroglycerin and dobutamine infusion in left ventricular dysfunction

The immediate therapy of severe left ventricular (LV) failure after acute myocardial infarction (AMI) frequently requires simultaneous preload reduction, pump output augmentation, and maintenance of systemic blood pressure. Therefore the effects of intravenous nitroglycerin (NG) and dobutamine (DB) were evaluated in 12 patients with severe LV failure following AMI. Nitroglycerin achieved salutary lowering of abnormally elevated LV filling pressure (23 to 14 mm Hg, p less than 0.001) while DB markedly augmented LV pump function (cardiac index rose from 1.7 to 2.5 L/min/m2, p less than 0.005). Notably, the combined infusion of NG + DB simultaneously decreased preload (LV filling pressure 23 to 14 mm Hg, p less than 0.001) and markedly enhanced LV pump performance (cardiac index increased from 1.7 to 2.4 L/min/m2, p less than 0.001). Minor decline in mean systemic blood pressure with NG (72 to 66 mm Hg, p less than 0.05) was rapidly reversed by DB addition (69 mm Hg, p greater than 0.05). Both agents were well tolerated without clinical or ECG evidence of myocardial ischemia or dysrhythmias. Thus the principally venodilator effects of NG minimize systemic hypotension while salutary augmentation of cardiac function in AMI with LV failure is achieved by NG + DB.