Neal Klein

Hemodynamic comparison of intravenous amrinone and dobutamine in patients with chronic congestive heart failure

Amrinone, a new inotropic agent, has been shown to be beneficial in patients with congestive heart failure. However, its hemodynamic effects have not been compared with those those of currently useful catecholamines. In this study, the effects of intravenously administered dobutamine and amrinone were compared in eight patients with severe chronic congestive heart failure. Dobutamine was infused with a maximal increase in cardiac index was reached for undesirable effects were produced. This dose was then continued for 8 hours. After a return of hemodynamic values to baseline level, amrinone was infused at a rate of 40 microgram/kg per min for 1 hour and then 10 microgram/kg per min for 24 hours. Both drugs significantly improved cardiac index while simultaneously decreasing systemic vascular resistance and right atrial and pulmonary wedge pressures (p less than 0.05). Initially no differences could be found between the drugs. However, with prolonged infusion amrinone produced a sustained improvement whereas dobutamine had a decreased effectiveness. Thus, amrinone is comparable in effect with the optimal dose of dobutamine and would appear to be an extremely promising drug in the acute treatment of severe congestive heart failure.

Long-term amrinone therapy in patients with severe heart failure: Drug-dependent hemodynamic benefits despite progression of the disease

Six patients with severe congestive heart failure refractory to conventional therapy, including vasodilators, were treated with oral amrinone for a mean duration of 41 weeks (range 20 to 72 weeks). At initiation of therapy, the cardiac index increased from 1.74 +/- 0.31 to 2.62 +/- 0.52 (mean +/- SD) liters/min/m2 (p less than 0.01) and pulmonary capillary wedge pressure decreased from 26.5 +/- 3.5 to 19.5 +/- 5.4 mm Hg (p less than 0.05). Symptoms were alleviated and exercise capacity increased from 5.9 +/- 2.9 to 11.5 +/- 4.5 minutes (p less than 0.05). During long-term therapy, exercise capacity remained constants in three patients whereas it decreased in three others. All patients demonstrated an increase in heart size. Withdrawal of amrinone therapy precipitated severe symptoms at rest and hemodynamic deterioration in all patients. The cardiac index decreased from 1.87 +/- 0.49 to 1.32 +/- 0.30 liter/min/m2 (p less than 0.05) and pulmonary capillary wedge pressure rose from 20.6 +/- 2.9 to 28.8 +/- 5.6 mm Hg (p less than 0.05). These changes were reversed by reinstitution of therapy. Thus, amrinone-dependent hemodynamic benefits were demonstrated during long-term therapy without tachyphylaxis. In addition, progression of the underlying cardiac disease was observed in every patient.

Comparison of oral propranolol and verapamil for combined systemic hypertension and angina pectoris: A placebo-controlled double-blind randomized crossover trial☆

The relative efficacies of oral verapamil, a calcium-entry blocking drug, and propranolol, a beta-adrenergic blocking drug, were compared in 12 patients who had both stable angina pectoris and mild to moderate systemic hypertension, using a placebo-controlled, double-blind, randomized crossover protocol. Compared with placebo, both propranolol and verapamil decreased the frequency of anginal attacks and the number of nitroglycerin tablets consumed, and increased exercise duration and total work; there were no significant differences in the antianginal effect of the two drugs. Both verapamil and propranolol reduced the supine and standing systolic and diastolic blood pressure measured at rest; compared with propranolol, however, verapamil had greater effects on standing diastolic blood pressure (p less than 0.002). Resting heart rate was reduced from placebo baseline with large doses of both drugs; compared with verapamil, however, propranolol exerted greater effects on resting heart rate and rate-pressure product. Plasma renin activity was increased from placebo baseline with verapamil (p less than 0.05), but was reduced with propranolol (p less than 0.05); no significant change in plasma aldosterone was seen with either drug. Verapamil appears to be a safe and effective treatment alternative to propranolol for relieving anginal symptoms, improving exercise tolerance, and reducing elevated systemic blood pressure in patients with both angina pectoris and mild to moderate systemic hypertension.

Labetalol therapy in patients with systemic hypertension and angina pectoris: effects of combined alpha and beta adrenoceptor blockade

Abstract The effects of oral labetalol, an alpha-beta adrenoceptor blocker, were evaluated in 10 patients with angina pectoris and hypertension. After 3 weeks of placebo, increasing doses of labetalol (300 to 1,200 mg/day) were given over 4 weeks followed by a rapid drug withdrawal phase. The frequency of anginal attacks and exercise tolerance were measured as were noninvasive indexes of left ventricular function (echocardiography, systolic time intervals), plasma renin activity and platelet function (aggregability). Compared with placebo, during labetalol therapy the frequency of anginal attacks was reduced, exercise time increased (from 351.6 ± 56.2 to 463.2 ± 45.2 seconds , P kilopond - meters , p mm Hg (mean ± Standard error of the mean) (p mm Hg (p beats / min (p mm Hg (p mm Hg (P beats / min (p

Beneficial Effects of Sublingual Nifedipine in Patients with Ischemic Heart Disease and Depressed Left Ventricular Function

The effects of sublingual nifedipine, a calcium channel beta-blocking drug, were assessed in eleven patients with coronary artery disease and depressed left ventricular function. All patients had a previous documented myocardial infarction. Specifically examined were the effects of a 20 mg dose on left ventricular ejection fraction as assessed through gated pool nuclear imaging. All patients had their anti-anginal drugs stopped forty-eight hours prior to inclusion in the study. Baseline resting determinations included a mean heart rate of 80 beats/minute, mean arterial pressure of 97 mmHg and an ejection fraction of 36 percent. Thirty minutes following a 20 mg sublingual dose, these parameters were reassessed. Mean heart rate increased to 89 beats/minute, p<0.02; mean arterial pressure decreased to 78 mmHg, p<.002; while ejection fraction increased to 48± 17 percent, p<.001. No adverse reactions were reported. These results demonstrate that nifedipine will acutely improve de creased left ventricular function in patients with coronary artery disease. While calcium blockers can significantly depress myocardial contractility, nifedipines ability to decrease mean arterial pressure and peripheral vascular resistance reduces afterload, improves myocardial performance which offsets any negative effects on contractility that may exist. This drug promises to be especially useful in patients with coronary artery disease and severely de pressed left ventricular function where agents such as beta-blockers are con traindicated.

Lidoflazine and propranolol combination treatment in chronic stable angina.

The short-term (1 month) and long-term (6 months) safety of combination lidoflazine-propranolol therapy was investigated in an open trial of 15 patients with stable angina of effort. The possible advantages of adding lidoflazine (ti trated to 360 mg daily) to patients having a therapeutic response to propranolol (80-400 mg daily) was also evaluated. Effects on non-invasive indexes of left ventricular function (echocardiography, systolic time intervals, radionuclide ventriculography) and exercise tolerance (treadmill exercise testing) were deter mined. There was no change in mean resting heart rate with the combination therapy, although one patient developed sinus bradycardia at a rate of 44 and had to have his propranolol dose reduced. Electrocardiographic analysis showed significant prolongation of the QTc intervals on lidoflazine-propranolol therapy compared to propranolol alone, with 3 patients having QTc interval prolongation to above .53 seconds, but there was no evidence of increased ar rhythmogenesis with the combination therapy compared to propranolol alone. Left ventricular end-diastolic volume index tended to rise with combination therapy. However, lidoflazine-propranolol therapy did not produce any signifi cant effects on resting ejection fraction determined by M-mode echocardio graphy or by radionuclide ventriculography. Radionuclide ventriculography determined peak exercise ejection fractions were also not significantly changed with combination therapy compared to propranolol alone. There were only small, insignificant improvements in exercise tolerance with the lidoflazine-pro pranolol combination treatment compared to propranolol alone. It is concluded that lidoflazine-propranolol combination therapy is generally safe but has the potential of causing serious adverse effects in certain patients, i.e. those with sick sinus disease, prolonged QTc intervals, and severe baseline left ventricular dysfunction, and that caution must be exercised in its use. Furthermore, it would appear that combination therapy provides only slight, if any, improve ments in exercise tolerance in patients with chronic stable angina having a ther apeutic response to oral propranolol.