Najam A. Awan

Sustained Reduction of Cardiac Impedance and Preload in Congestive Heart Failure with the Antihypertensive Vasodilator Prazosin

To elucidate the hemodynamic effects of prazosin, an antihypertensive agent, in congestive heart failure, we studied 10 patients with ischemic cardiomyopathy and severe ventricular dysfunction. After an oral dose of 2 to 7 mg, heart rate was unchanged (P greater than 0.05). One hour after prazosin administration, mean arterial pressure declined from 95 to 78 mm Hg (P less than 0.001); left ventricular filling pressure declined from 30 to 18 mm Hg (P less than 0.001), cardiac index increased from 2.1 to 2.9 liters per minutes per square meter (P less than 0.001), and systemic vascular resistance fell from 2074 to 1156 dynes sec cm-5 (P less than 0.001). In both forearms vascular resistance and venous tone were reduced (86 to 48 mm Hg per ml per 100 g per minute, and 59 to 18 mm Hg per ml, respectively [P less than 0.001]). All responses persisted for a least six hours (P less than 0.01). Prazosin benefits severe congestive heart failure by inducing a sustained fall of both cardiac preload and impedance.

Efficacy of ambulatory systemic vasodilator therapy with oral prazosin in chronic refractory heart failure. Concomitant relief of pulmonary congestion and elevation of pump output demonstrated by improvements in symptomatology, exercise tolerance, hemodynamics and echocardiography.

The long-term efficacy of the new oral vasodilator, prazosin (PZ), was evaluated in nine patients with refractory heart failure due to chronic coronary heart disease. Ventricular function was assessed by cardiac catheterization, echocardiography, and treadmill testing; symptomatic evaluation was carried out for two to four months. One hour following 2-7 mg PZ, control left ventricular filling pressure was reduced (32 to 18 mm Hg, P < 0.001) for a 6 hour period. After two weeks of PZ 2 to 7 mg four times daily, echographic end-diastolic dimension fell (5.7 to 5.4 cm, P < 0.001) whileshortening fraction increased (27.6 to 30.2%, P < 0.005). Treadmill exercise duration increased from 209 to 317 seconds (P < 0.001). Symptoms diminished throughout the duration of follow-up (mean 94 days) with improvement in NYHA functional class (3.7 to 2.2, P < 0.001). Thus, prazosin possesses sustained nitroprusside-like balanced dilator actions on the systemic arterialand venous systems and is effective in the ambulatory management of chronicsevere heart failure.

A COOPERATIVE MULTICENTER STUDY OF CAPTOPRIL IN CONGESTIVE HEART FAILURE: HEMODYNAMIC EFFECTS AND LONG-TERM RESPONSE

The acute hemodynamic effects, long-term clinical efficacy, and safety of the oral angiotensin-converting enzyme inhibitor, captopril, were assessed in a multicenter cooperative study of 124 patients with heart failure resistant to digitalis and diuretics. The cardiac status of most patients was deteriorating prior to the study. Favorable acute hemodynamic effects consistently occurred with captopril. Maximal mean percentage increases in cardiac index, stroke index, and stroke work index were, respectively, 35%, 44%, and 34%. Systemic and pulmonary vascular resistances were each decreased by approximately 40%, as were the filling pressures of the right and left heart. Infusion of nitroprusside in some of the same patients to an end point of a pulmonary capillary wedge pressure of 12 to 18 mm Hg (equivalent to that after captopril) revealed no significant difference in the effect of either drug on the other hemodynamic parameters. Recatheterization after 8 weeks of captopril therapy revealed sustained hemodynamic changes. Significant and sustained improvements in clinical status were observed in most patients as measured by changes in New York Heart Association (NYHA) functional classification and exercise tolerance times. Seventy-nine percent of patients for whom there were adequate NYHA class data improved. Twenty percent remained unchanged and 1% deteriorated. Those patients who had both pretreatment and post-treatment exercise stress testing exhibited a highly significant mean increase in exercise tolerance times of 34% (317 +/- 32 seconds pretreatment to 425 +/- 34 seconds, final measurement). There was no evidence of tachyphylaxis over an 18-month period.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of effects of nitroprusside and prazosin on left ventricular function and the peripheral circulation in chronic refractory congestive heart failure.

We compared cardiocirculatory actions of nitroprusside (NP) to prazosin (PZ) in eleven chronic coronary patients with refractory congestive heart failure. Each drug equally lowered systemic arterial pressures mildly while heart rate was unaltered. NP decline (P < .001) in left ventricular filling pressure (28 to 17 mm Hg) and rise (P < .005) in cardiac index (2.20 to 2.96 L/min/m2) were similar to PZ (30 to 17) and (2.08 to 3.00). PZ and NP equally enhanced cardiac efficiency of stroke work and myocardial oxygen consumption index. Total systemic vascular resistance declined (P < .001) the same with NP and PZ. Forearm vascular resistance (FVR) and venous tone (FVT) diminished equally with NP and PZ. Similar FVR/FVT percent changes of 0.88 and 0.64 with NP and PZ indicated relatively balanced systemic arteriolovenous relaxation. Sinze PZ effects persisted six hours with symptomatic improvement, oral PZ is the best vasodilator for long-term use, extending in-hospital NP-like actions to ambulatory heart failure therapy.

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.

Combined dopamine and nitroprusside therapy in congestive heart failure. Greater augmentation of cardiac performance by addition of inotropic stimulation to afterload reduction.

The hemodynamic benefits of combining administration of dopamine with nitroprusside (NP) were evaluated in nine patients with chronic congestive heart failure due to ischemic, idiopathic myocardial or valvular cardiac disease. NP alone (68 μg/min) produced decline in left ventricular end-diastolic pressure (LVEDP) from 25.4 to 14.1 mm Hg (P < 0.01) but modest increase in cardiac index (CI) from 2.41 to 3.02 L/min/m2 (P < 0.05). Dopamine alone (6 μg/kg/min) caused an elevation of CI to 3.36 (P < 0.01) but without decrease of LVEDP. Simultaneous infusion of the two agents resulted in favorable alterations in both hemodynamic variables: LVEDP decreased to 15.7 (P < 0.01) and CI increased to 3.52 (P < 0.01). It is concluded that dopamine substantially enhances the effectiveness of nitroprusside therapy in congestive heart failure by providing concomitantly the principal beneficial actions of the vasodilator and dopamine used separately. Thus combined dopamine with NP treatment considerably raises low CI while markedly reducing elevated LVEDP and provides a potentially efficacious pharmacologic modality for the treatment of severe congestive heart failure due to left ventricular dysfunction.

Importance of maintaining systemic blood pressure during nitroglycerin administration for reducing ischemic injury in patients with coronary disease. Effects on coronary blood flow, myocardial energetics and left ventricular function

Abstract Because of the controversy concerning the effects on myocardial ischemia of maintaining systemic pressure concomitant with administration of nitroglycerin, this study was undertaken of the actions of nitroglycerin, with and without simultaneous phenylephrine infusion, on coronary blood flow, myocardial energetics and left ventricular function in 17 patients with multivessel coronary artery disease. Five minutes after sublingual administration of 0.4 mg of nitroglycerin, mean arterial pressure, left ventricular filling pressure, cardiac index and coronary sinus blood flow were reduced ( P P P > 0.05) from control values by the addition of phenylephrine to nitroglycerin. Because myocardial oxygen extraction decreased while coronary sinus flow increased, the phenylephrine-induced increase in coronary flow was not due to augmented cardiac oxygen demands. Thus, preservation of systemic pressure concomitant with nitroglycerin enhances myocardial perfusion. From these findings, with greater nitroglycerininduced decreases in mean arterial pressure and coronary flow in patients with acute ischemia, it appears that phenylephrine with nitroglycerin may particularly improve myocardial energetics.

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.

Effects of prazosin on forearm resistance and capacitance vessels.

The effects of oral prazosin on the peripheral circulation were evaluated in 10 subjects, including 7 patients with chronic congestive failure due to coronary heart disease. To achieve this purpose the actions of 30 to 50 µg/kg body weight prazosin were assessed on both the forearm arteriolar and venous beds simultaneously with the use of the limb plethysmographic technique. Prazosin produced marked decline of forearm venous tone (FVT) from 44.5 ± 12.3 to 14.3 ± 3.1 mm Hg/ml (p < 0.01) concomitant with marked decrease in forearm vascular resistance (FVR) from 70.2 ± 11.4 to 48.4 ± 4.9 mm Hg/ml/100 gm/min (p < 0.05) which persisted for at least 60 mins without change in heart rate. These findings, demonstrating that prazosin induces systemic venodilation and peripheral arteriolodilation, indicate potential benefits of the oral drug for relief of pulmonary congestion and elevations of cardiac output in patients with chronic congestive heart failure.

Reduction of ischemic injury by sublingual nitroglycerin in patients with acute myocardial infarction.

SUMMARY The effect of sublingual nitroglycerin (NTG) on myocardial ischemic injury was evaluated in eleven patients with acute anterior myocardial infarction. Precordial 35-lead ST-segment maps were obtained in each patient immediately before and 3-10 minutes after 0.4 mg sublingual NTG. The following measurements were made from each ST map: N-ST (number of leads showing ST elevation < 1 mm), ΣST (total ST elevation in all leads), ST (average ST-segment elevation in those leads with < 1 mm elevation). Following 0.4 mg sublingual NTG evidence of myocardial ischemic injury as assessed by ST-segment mapping decreased in association with reduction of heart rate × systolic blood pressure product (10.80 × 103 to 9.49 × 103, P < 0.001). Group mean values diminished significantly for N-ST (18.1 to 14.4, P < 0.001), 2ST (37.9 to 30.1, P < 0.005) and ST (1.7 to 1.4, P < 0.001). Evaluation performed by the technique of precordial ST-segment mapping suggests that sublingual nitroglycerin in a commonly employed clinical dose is associated with evidence of reduced ischemic cardiac injury in patients with acute myocardial infarction. This effect appears to be related to reduction of myocardial oxygen demand by the nitrate.