The evaluation of drug-induced changes in cardiac inotropy in dogs: Results from a HESI-sponsored consortium.

INTRODUCTION: Drug-induced effects on the cardiovascular system remain a major cause of drug attrition. While hemodynamic (blood pressure (BP) and heart rate (HR)) and electrophysiological methods have been used in testing drug safety for years, animal models for assessing myocardial contractility are used less frequently and their translation to humans has not been established. The goal of these studies was to determine whether assessment of contractility and hemodynamics, when measured across different laboratories using the same protocol, could consistently detect drug-induced changes in the inotropic state of the heart using drugs known to have clinically relevant positive and negative effects on myocardial contractility. METHODS: A 4×4 double Latin square design (n=8) design using Beagle dogs was developed. Drugs were administrated orally. Arterial blood pressure, left ventricular pressure (LVP) and the electrocardiogram were assessed. Each of the six laboratories studied at least 2 drugs (one positive inotrope (pimobendan or amrinone) and one negative inotrope) (itraconazole or atenolol) at 3 doses selected to match clinical exposure data and a vehicle control. Animals were instrumented with an ITS telemetry system, DSI's D70-PCTP system or DSI's Physiotel Digital system. Data acquisition and analysis systems were Ponemah, Notocord or EMKA. RESULTS: Derived parameters included: diastolic, systolic and mean arterial BP, peak systolic LVP, HR, end-diastolic LVP, and LVdP/dtmax as the primary contractility index. Blood samples were drawn to confirm drug exposures predicted from independent pharmacokinetic studies. Across the laboratories, a consistent change in LVdP/dtmax was captured despite some differences in the absolute values of some of the hemodynamic parameters prior to treatment. DISCUSSION: These findings indicate that this experimental model, using the chronically instrumented conscious dog, can accurately and consistently detect changes in cardiac contractility, across multiple sites and instrumentation systems, and that data obtained in this model may also translate to clinical outcomes.

Effects of inotropic drugs on mechanical function and oxygen balance in postischemic canine myocardium: comparison of dobutamine, epinephrine, amrinone, and calcium chloride.

Brief ischemic episodes that induce myocardial and coronary endothelial dysfunction may alter the responses to inotropic drugs. To determine the effects of inotropic drugs in stunned myocardium, the coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and regional mechanical function in response to intracoronary dobutamine, epinephrine, amrinone, and calcium chloride (CaCl2) were measured before (normal) and 30 min after a 15-min-period occlusion of the left anterior descending artery (stunned) in an open-chest canine model. Percent segment shortening (%SS) and post-systolic shortening (%PSS) were determined. Myocardial extraction of oxygen (EO2) and lactate (E(lac)) was calculated. The inotropic drugs increased %SS, CBF, and MVO2 in normal myocardium. Epinephrine and amrinone decreased, while dobutamine and CaCl2 did not affect EO2. The ischemia and reperfusion itself significantly reduced %SS and E(lac), and increased %PSS. In stunned myocardium, the responses to inotropic drugs were not significantly altered, except that they progressively reduced %PSS and epinephrine did not affect EO2. These findings indicate that a brief episode of ischemia does not affect the mechanical and metabolic coronary flow responses to inotropic drugs, although it abolishes direct vasodilator responses to epinephrine.

Effects of Inotropic Drugs on Mechanical Function and Oxygen Balance in Postischemic Canine Myocardium: Comparison of Dobutamine, Epinephrine, Amrinone, and Calcium Chloride

Brief ischemic episodes that induce myocardial and coronary endothelial dysfunction may alter the responses to inotropic drugs. To determine the effects of inotropic drugs in stunned myocardium, the coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and regional mechanical function in response to intracoronary dobutamine, epinephrine, amrinone, and calcium chloride (CaCl2) were measured before (normal) and 30 min after a 15-min-period occlusion of the left anterior descending artery (stunned) in an open-chest canine model. Percent segment shortening (%SS) and post-systolic shortening (%PSS) were determined. Myocardial extraction of oxygen (EO2) and lactate (E(lac)) was calculated. The inotropic drugs increased %SS, CBF, and MVO2 in normal myocardium. Epinephrine and amrinone decreased, while dobutamine and CaCl2 did not affect EO2. The ischemia and reperfusion itself significantly reduced %SS and E(lac), and increased %PSS. In stunned myocardium, the responses to inotropic drugs were not significantly altered, except that they progressively reduced %PSS and epinephrine did not affect EO2. These findings indicate that a brief episode of ischemia does not affect the mechanical and metabolic coronary flow responses to inotropic drugs, although it abolishes direct vasodilator responses to epinephrine.

Effects of preemptive therapy with milrinone or amrinone on perioperative platelet function and haemostasis in patients undergoing coronary bypass grafting.

Preemptive therapy with a phosphodiesterase III inhibitor preserves cardiac function and oxygen transport after cardiac surgery, and its safety on platelet function and haemostasis must be verified. We examined the effects of preemptively administered milrinone or amrinone on platelet function and haemostasis. In 45 cardiac surgery patients, we randomly administered milrinone 50 microg/kg plus 0.5 microg/kg/min for 10 hours, amrinone 1.5 mg/kg plus 10 microg/kg/min infusion for 10 hours, or placebo at release of aortic cross-clamp. Whole blood platelet aggregation, haematological values, and postoperative chest drainage were examined. Three patients in the placebo, 1 patient in the amrinone, and 2 patients in the milrinone groups received allogenic blood transfusion (654 +/- 365 ml) intraoperatively, but no patient postoperatively. The mean platelet counts 3 days postoperative in the milrinone and amrinone groups did not significantly differ from the placebo group (10.9 +/- 3.3 and 12.1 +/- 3.8, vs. 12.1 +/- 3.4x10(4) per cubic millimeter, respectively), and chest-tube drainage in the first 24 hours did not significantly differ (450 +/- 156 and 391 +/- 184, vs. 448 +/- 140 ml, respectively). Although there were changes in platelet aggregation consequent to surgery there was no significant differences in platelet aggregation or other haematological values among the three groups. Preemptive therapy of milrinone or amrinone does not deteriorate perioperative platelet function and haemostasis beyond surgical interventions.

Effects of amrinone on bilateral renal ischemia/reperfusion injury.

Renal ischemia/reperfusion injury could arise as a consequence of clinical conditions such as renal transplantation, shock, cardiac arrest, hemorrhage and renal artery surgery. In this experimental study, we aimed to determine the preventive effects of amrinone on bilateral renal ischemia/reperfusion injury in rats. A total of 60 Wistar-albino rats were divided into six groups ( n=10). Midline laparotomies were made under ketamine anesthesia. In the sham, amrinone1 and amrinone2 without ischemia (AWI1 and AWI2) groups saline, 5 and 10 mg/kg of amrinone was infused, respectively. In the ischemia, ischemia plus amrinone1 (IPA1) and ischemia plus amrinone2 (IPA2) groups, saline and 5 and 10 mg/kg of amrinone was infused, respectively, at the beginning of reperfusion, subsequent to 45 min of bilateral renal artery occlusion. Following 6 h of reperfusion, blood was drawn to study serum BUN and creatinine and a bilateral nephrectomy was done to determine tissue malonyldialdehyde ( MDA) and myeloperoxidase (MPO) levels. The results were analysed by Mann-Whitney U-test. The parameters studied were statistically higher in the ischemia group compared with the other groups ( P<0.05 for each comparison), indicating renal I/R injury. These parameters were lower in the amrinone without ischemia groups (AWI1 and AWI2) than in the sham group, however there were no significant differences between the groups ( P>0.05, for each comparison). The treatment groups IPA1 and IPA2 had statistically similar results compared with the sham group, showing the preventive effect of amrinone on renal I/R injury at the given doses. We conclude that amrinone prevented experimental renal ischemia/reperfusion injury in rats, independently of the administered doses. This preventive effect of the agent could depend on its effect of regulating the microcirculation, in decreasing intracellular calcium and in preventing neutrophil activation. We propose that this preventive effect of amrinone - which has gained clinical application especially in cases of cardiac insufficiency - could also be exploited in clinical conditions related with renal ischemia/reperfusion.

[Effects of amrinone in patients undergoing off-pump coronary artery bypass grafting].

We evaluated the effect of amrinone in 41 patients undergoing off-pump coronary artery bypass grafting(CABG) retrospectively. Amrinone was intravenously administered at the rate of 5 mcg.kg-1.min-1 after coronary artery anastomosis (A 1 group: 11 cases) or after induction of anesthesia(A 2 group: 13 cases). The hemodynamic variables and use of concomitant drugs were compared among A 1, A 2 and the non-amrinone group (control group: 17 cases). Hemodynamics was measured before, during, after coronary artery anastomosis, and after the chest closure. Catecholamine and vasodilator were used to maintain mean arterial pressure (> 60 mmHg) and cardiac index(> 3.0 l.min-1.m-2). Mean pulmonary artery pressure, right atrial pressure and pulmonary artery wedge pressure were significantly higher during anastomosis than before anastomosis in control and A 1 group, but no significant changes in these parameters were observed in A 2 group. In addition, these variables increased significantly after chest closure in control group, but were unchanged in A 1 and A 2 groups. Patients with concomitant use of catecholamine and vasodilator in A 2 group were fewer than those in control and A 1 group. In conclusion, in the patients undergoing off-pump CABG, infusion of amrinone was recommended from the end of the induction of anesthesia.

The efficacy of preemptive Milrinone or Amrinone therapy in patients undergoing coronary artery bypass grafting.

UNLABELLED: Acute deterioration in ventricular function and oxygen transport is common after cardiac surgery. We hypothesized that milrinone or amrinone may reduce their occurrence and catecholamine requirements and increase cellular enzyme levels in patients undergoing coronary artery bypass. In 45 patients, we randomly administered milrinone 50 microg/kg plus 0.5 microg x kg(-1) x min(-1) infusion for 10 h, amrinone 1.5 mg/kg plus 10 microg x kg(-1) x min(-1) infusion for 10 h, or placebo at release of aortic cross-clamp. Hemodynamic variables, dopamine requirement, and laboratory values were recorded. At the postoperative nadir, stroke volume index was higher in the Milrinone and Amrinone groups (mean +/- SD, 27.8 +/- 4.0 and 26.1 +/- 3.2 vs. 20.4 +/- 5.1 mL x min (-1) x m(-2) per beat, P < 0.0001), and oxygen transport index was higher (354.7 +/- 57.8 and 353.7 +/- 91.2 vs 283.0 +/- 83.9 mL. min(-1) x m(-2), P = 0.009). The postoperative dopamine requirement was less (6.6 +/- 2.7 and 6.8 +/- 2.6 vs 10.4 +/- 2.0 mg/kg, P < 0.008), and postoperative serum lactate, alanine and aspartate aminotransferase, lactate dehydrogenase, creatinine kinase, C-reactive protein, and glucose levels were less (P < 0.01). The mean postoperative heart rate was faster in the Milrinone group than in the Amrinone and Placebo groups (96.8 +/- 10.3 vs. 86.9 +/- 9.5 and 87.8 +/- 10.8 bpm, P < 0.01). Milrinone and amrinone administered preemptively reduce postoperative deterioration in cardiac function and oxygen transport, dopamine requirement, and increases in serum lactate, glucose, and enzyme levels, although milrinone may increase heart rate. IMPLICATIONS: Preemptive milrinone or amrinone administration before separation from cardiopulmonary bypass in cardiac surgical patients not only ameliorates postoperative deterioration in cardiac function and oxygen transport, but also reduces dopamine requirement and increases serum lactate, glucose, and cellular enzyme levels, although milrinone may increase heart rate.

Comparison of enoximone, amrinone, or levosimendan enriched St. Thomas' hospital cardioplegic solutions used for myocardial preservation in isolated guinea pig hearts.

Myocardial contractile function after cardioplegic arrest is often depressed and an ideal cardioplegic solution has not been developed yet. The aim of this study was to assess the efficacy of phosphodiesterase III inhibitors, amrinone and enoximone, and levosimendan, a novel Ca2+ sensitizing agent, on recovery of hearts after normothermic cardioplegic arrest when added to the St. Thomas' hospital cardioplegic solution. In the control group, isolated guinea pig hearts were perfused in Langendorff apparatus and arrested with standard St. Thomas' solution. In other groups, amrinone (10(-5) mol.L-1), levosimendan (10(-5) mol.L-1), or enoximone (10(-4) mol.L-1) were added to the cardioplegic solution. In all hearts, intraventricular pressure, +dp/dtmax, -dp/dtmax, area under pressure-time curve, heart rate, coronary flow, lactate dehydrogenase and creatine kinase enzyme leakage, and oxygen consumption were measured. In the enoximone group, contractility force and +dp/dtmax, were found to be significantly high in the reperfusion and inotropic periods in comparison with other groups (p < 0.05). -dp/dtmax and area under contractility-time curve values were significantly high in inotropic period in enoximone group (p < 0.05). No statistically significant difference was noted in other groups. Cardioplegic solution enrichment with enoximone augmented mechanic functions in reperfusion period. No positive effect of amrinone or levosimendan was observed in this study.

[Differences in hemodynamic effects of amrinone, milrinone and olprinon after cardiopulmonary bypass in valvular cardiac surgery].

The differences in hemodynamic effects of amrinone, milrinone and olprinone were evaluated in 46 patients for valvular cardiac surgery after cardiopulmonary bypass (CPB). Patients were randomly allocated to three groups; group A with amrinone infusion (17 patients); group M with milrinone infusion (15 patients); and group O with olprinone infusion (14 patients). Each drug was administrated as a single dose into the venous reservoir of the CPB circuit 15 min prior to the end of emergence from CPB, followed by continuous infusion. Hemodynamic parameters were measured at the time of preCPB (C0), just after the end of CPB (C1), one hour after the termination of CPB (C2) and after the chest closure (C3). Catecholamines were used in order of dopamine, norepinephrine and dobutamine. These doses were modulated to maintain the cardiac index > 3.0 l.min-1.m-2 by each anesthesiologist. Hemodynamic parameters (at C0, C1, C2 and C3) and the doses of cathecholamine (at C1, C2 and C3) were compared among the 3 drugs. The systolic blood pressure in group M was significantly higher than that of group A and group O after chest closure. In group M and A, the systolic blood pressure showed a significant increase after CPB. On the other hand, the systolic blood pressure showed no significant change in group O after CPB. Three drugs showed no significant difference in the dosages of catecholamines used.

Topical application of amrinone (a selective phosphodiesterase III inhibitor) for relief of vasospasm.

BACKGROUND: Amrinone, a selective phosphodiesterase III inhibitor, is an agent that possesses a combination of positive inotropic and vasodilating properties as a result of preventing the degradation of cAMP, and it has recently been licensed for the treatment of heart failure. The aim of this study was to investigate the potential therapeutic application of amrinone to resolve vasospasm, which is the major problem in reconstructive surgery. In this study its effect was compared with that of lidocaine, the most commonly used topical vasodilating agent clinically. MATERIALS AND METHODS: The probe of an ultrasonic transit-time volume flowmeter was applied to the femoral artery of rats to measure blood flow. After a baseline recording was obtained, 0.03 ml of epinephrine was applied topically to induce vasospasm. The vessels were then immersed in 1 ml of amrinone (5 mg/ml), 10% lidocaine hydrochloride, or normal physiological saline solution for 1 min in an attempt to resolve the spasm. In another group of animals, no solution was used following administration of epinephrine to allow observation of spontaneous resolution of the vasospasm over time. RESULTS: The results showed an essentially immediate spasm-resolving effect in both the amrinone group and the lidocaine group. The amrinone group showed a significantly greater degree of maximum increase in blood flow than the lidocaine group. The effect of lidocaine decreased with time, whereas amrinone had a more lasting effect. CONCLUSIONS: The findings suggest that amrinone could be used as an effective topical vasodilating agent to resolve vasospasm in reconstructive surgery.

[General anesthesia for a patient with primary aldosteronism complicated with hypertrophic nonobstructive cardiomyopathy].

We report a patient with primary aldosteronism (PA) complicated with hypertrophic nonobstructive cardiomyopathy (HNCM) who underwent resection of a left adrenal tumor. Amrinone was administered to improve the features of congestive heart failure induced by retention of body fluid. Maintaining adequate preload and afterload and preventing excessive increases in contractility are important in the anesthetic management of patients with hypertrophic obstructive cardiomyopathy (HOCM). Although the preoperative diagnosis may be HNCM, stenosis of the left ventricular outflow tract may occur due to hemodynamic changes during surgery. Therefore amrinone is not often used for patients with HNCM. We inserted a pulmonary arterial catheter (Swan-Ganz CCO Thermodilution Catheter) and measured the cardiac output continuously to monitor hemodynamic changes. The symptoms of pulmonary edema were diminished one month after the surgery. These findings suggest that the increased blood volume induced by PA is a main factor aggravating preoperative congestive heart failure with HNCM.

Concurrent administration of amrinone with nitric oxide most improves PaO2/FiO2 in acute respiratory and cardiac failure.

A 55-year-old man developed acute respiratory failure, pulmonary hypertension and left heart failure due to acute myocardial infarction. Nitric oxide (NO) inhalation improved arterial oxygenation, decreased pulmonary arterial pressure and increased cardiac output (CO), but combined use of dobutamine with NO produced increases in pulmonary arterial pressure and pulmonary capillary wedge pressure (PCWP). In this patient, amrinone decreased pulmonary arterial pressure and PCWP, and increased PaO2/FiO2 effectively while increasing CO. Combined use of inhaled NO and intravenous amrinone may have beneficial effects for a patient with acute respiratory and cardiac failure.

Amrinone versus dopamine and nitroglycerin in neonates after arterial switch operation for transposition of the great arteries.

OBJECTIVE: To compare the efficacy and safety of amrinone and a combination of dopamine and nitroglycerin in neonates after reconstructive surgery for transposition of the great arteries. DESIGN: A prospective, randomized, double-blind study. SETTING: Pediatric intensive care unit in a university hospital. PARTICIPANTS: Thirty-five neonates with transposition of the great arteries. INTERVENTIONS: A loading dose of amrinone, 2 mg/kg, followed by a maintenance infusion of 7.5 microg/kg/min, were administered to 16 neonates before separation from cardiopulmonary bypass. The remaining 19 patients were administered a combination of dopamine, 5 microg/kg/min, and nitroglycerin, 1 microg/kg/min. An open-label epinephrine infusion was administered in both groups as required. MEASUREMENTS AND MAIN RESULTS: The circulatory state of the patients was evaluated from 4 to 18 hours after cardiopulmonary bypass. The systemic blood flow index, calculated using the Fick principle, was higher in the amrinone group (1.7+/-0.5 L/min/m2 [mean +/- SD]) compared with the dopamine-nitroglycerin group (1.4+/-0.4 L/min/m2; p < 0.04). The systemic vascular resistance in the amrinone group was lower (26+/-8 Wood units x m2) than in the dopamine-nitroglycerin group (35+/-12 Wood units x m2; p < 0.02). The oxygen extraction ratio was higher in the dopamine-nitroglycerin group (0.34+/-0.08) compared with the amrinone group (0.28+/-0.06; p < 0.02). Lower platelet counts were observed in the amrinone group, but no difference in hemorrhagic complications was seen between the groups. CONCLUSION: With the dosage regimen used, supplemented with epinephrine, amrinone provides a higher cardiac output and more favorable oxygen dynamics than a combination of dopamine and nitroglycerin.

Diuretic effect of phosphodiesterase inhibitors depends on baseline renal function in patients with congestive heart failure.

We examined the diuretic effects of phosphodiesterase inhibitors in heart failure patients with and without renal failure. We found that, despite the improvement in central hemodynamics, phosphodiesterase inhibitors do not necessarily facilitate diuresis in heart failure in patients with concomitant renal failure.

[Endothelial-derived nitric oxide mediates the peripheral vasodilatory effects of amrinone in humans].

Amrinone, which is used for the treatment of acute congestive heart failure, has vasodilatory and positive inotropic effects through the increment of intracellular cyclic adenosine monophosphate. Recent in vitro investigations have shown that amrinone has an endothelium-dependent vasodilatory effect. The present study examined whether amrinone shows this endothelium-dependent vasodilatory effect in human peripheral vessels. Forearm blood flow during intra-arterial infusion of graded doses (12.5, 25, 50, 100, 200 micrograms/min) of amrinone was measured using plethysmography in 10 healthy subjects without organic vascular disease before and after nitric oxide synthase blocking with NG-monomethyl-L-arginine (L-NMMA, 400 mumol). The graded dose of amrinone produced progressive increases in amrinone plasma concentrations, and a dose over 100 micrograms/min caused amrinone plasma concentrations of more than 1.0 microgram/ml. The increase in forearm blood flow in response to amrinone was significantly depressed after L-NMMA doses of less than 100 micrograms/min, but the increase in forearm blood flow during infusion of higher doses (100, 200 micrograms/min) was not affected by L-NMMA. These results suggest that endothelial-derived nitric oxide may partially contribute to amrinone-induced vasodilation in humans. Thus, the vasodilatory effect of amrinone might be impaired in patients with endothelial dysfunction.

A bolus dose of 1.5 mg/kg amrinone effectively improves low cardiac output state following separation from cardiopulmonary bypass in cardiac surgical patients.

BACKGROUND: The aim of this study was to evaluate the efficacy of 1.5 mg/kg bolus of amrinone on low cardiac output (CO) state following emergence from cardiopulmonary bypass (CPB) in cardiac surgical patients. METHODS: Immediately after emergency from CPB, 14 patients with a cardiac index (CI) less than 2.2 l.min-1.m-2 despite administration of inotropes and nitroglycerin, received 1.5 mg/kg amrinone over 3 min without changing catecholamine infusion rates (amrinone group). Hemodynamics and left ventricular short axis views with transesophageal echocardiography were recorded at baseline, 3, 4, and 10 min following amrinone administration. Left ventricular filling volumes were maintained constant by volume reinfusion from the CPB reservoir. We matched the data of the amrinone group with the other 14 patients who did not receive amrinone (non-amrinone group) to evaluate the efficacy of amrinone in low CO state. RESULTS: At baseline, CI (1.8 +/- 0.1 l.min-1.m-2) in the amrinone group was significantly lower than CI (3.0 +/- 0.2) in the non-amrinone group. Following amrinone administration, CI and velocity of circumferential fibershortening corrected for heart rate (Vcfc) significantly increased, and systemic vascular resistance index and pulmonary vascular resistance index significantly decreased from the baseline within 10 min without changes in heart rate, mean arterial blood pressure, or pulmonary artery occlusion pressure, and became equivalent with those of the non-amrinone group. CONCLUSIONS: A 1.5 mg/kg amrinone loading dose to patients in a low CO state, despite catecholamine therapy immediately after emergence from CPB, effectively improves ventricular function when loading conditions are maintained constant.

Amrinone, a selective phosphodiesterase III inhibitor, improves microcirculation and flap survival: a comparative study with prostaglandin E1.

BACKGROUND: Amrinone, a selective phosphodiesterase (PDE) III inhibitor, is a newly developed agent that possesses a combination of positive inotropic and vasodilating properties as a result of preventing the degradation of cAMP and it has recently been licensed for treatment of heart failure alone. Amrinone is expected to be useful for the treatment not only of heart failure but also of peripheral circulatory disorders, including vascular disease, and for ischemic flaps, because it improves microcirculatory hemodynamics. To investigate potential therapeutic applications of amrinone, we evaluated its ability to improve microcirculatory hemodynamics and flap survival. MATERIALS AND METHODS: The rat skinfold chamber technique was employed to quantify microcirculation directly in vivo. The improved survival area of random flaps in rats treated with amrinone was examined to assess therapeutic efficacy of this drug. Its effects were compared with those of prostaglandin E1 (PGE1), which has been widely approved as an agent for improving hemodynamics. RESULTS: Microcirculatory blood flow and flap survival area were significantly increased in both amrinone- and PGE1-treated animals, compared to the saline-treated controls. The ameliorating effects of amrinone were comparable to those of PGE1. CONCLUSIONS: The results of this study suggest amrinone to be a potentially useful drug not only for treating heart failure but also for improving microcirculation in patients with vascular diseases and for postoperative care after reconstructive surgery.

Resultados a corto plazo con amrinona o digoxina en insuficiencia cardiaca / Short term response with amrinone or digoxin in congestive heart failure

Objetivo: Determinar si es más eficaz la administración de amrinona que la de digoxina en la fase aguda de la insuficiencia cardiaca congestiva moderada y severa. Material y métodos. Se estudiaron dos grupos con 10 pacientes cada uno. Uno recibió 0.25 a 0.5 mg de digoxina intravenosa cada 8 horas; y el otro, 0.75 mg/kg de amrinona en bolo y 5 a 10 µg/kg/minuto como dosis de mantenimiento. Se realizó medición basal de tensión arterial sistólica, tensión arterial diastólica, frecuencia cardiaca y frecuencia respiratoria; así como a los 20, 60, 120, 180 y 1440 minutos posteriores a la administración de los medicamentos. Se utilizó t de Student, informando los promedios y la desviación estándar. Resultados: En promedio, en el grupo que recibió digoxina la tensión arterial sistólica basal fue de 139 ñ 5.6 mm Hg y a los 60 minutos de 130 ñ 9.4 (p< 0.02); la tensión arterial diastólica basal de 89 ñ 8.7 mm Hg y a los 60 minutos de 81 ñ 8.75 (p< 0.05); la frecuencia cardiaca basal de 126 ñ 6.9 latidos/minuto y a los 60 minutos de 113 ñ 10.5 (p< 0.001). En promedio, en el grupo que recibió amrinona la tensión arterial sistólica basal fue de 146 ñ 8.4 mm Hg y a los 20 minutos de 135 ñ 9.7 (p< 0.05); la tensión arterial diastólica basal de 90 ñ 4.7 mm Hg y a los 20 minutos de 83 ñ 6.7 (p< 0.02); la frecuencia cardiaca basal de 127.5 ñ 7.1 latidos/minuto y a los 20 minutos de 108.5 ñ 17 (p < 0.0001). Conclusiones: La amrinona es más eficaz que la digoxina en la fase aguda de la insuficiencia cardiaca congestiva moderada y severa