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PubMed1993

Selective pulmonary and systemic vasodilator effects of amrinone in children: new therapeutic implications.

OBJECTIVES: The present study was performed to determine the systemic and pulmonary hemodynamic effects of amrinone in infants and children with a cardiac left to right shunt to determine if there is a beneficial effect on the pathophysiology of this condition. BACKGROUND: Amrinone is a bipyridine derivative with inotropic and vasodilator effects that have not been systematically evaluated in the pediatric patient with increased pulmonary blood flow. METHODS: Nineteen patients (aged 2 months to 8.3 years) with one or more left to right shunts were evaluated during cardiac catheterization with direct hemodynamic measurements made before and 10 min (peak effect) after administration of a bolus injection of amrinone, 3 mg/kg body weight. The Fick method was used to calculate pulmonary and systemic blood flow, and resistances were then calculated. RESULTS: In group A, five patients with normal pulmonary artery pressure and resistance, amrinone significantly reduced mean pulmonary artery pressure by 19%, mean left atrial pressure by 39% and systemic vascular resistance by 17%. In group B, seven patients with pulmonary artery hypertension (mean pulmonary artery pressure > 20 mm Hg) and normal pulmonary vascular resistance (total pulmonary resistance < or = 3 Wood U.m2), amrinone significantly reduced the pulmonary artery pressure by 27%, systolic aortic pressure by 5%, mean aortic pressure by 12%, pulmonary arteriolar resistance by 36% and total pulmonary vascular resistance by 26%. In group C, seven patients with pulmonary artery hypertension (mean pulmonary artery pressure > 20 mm Hg) and elevated pulmonary vascular resistance (total pulmonary resistance > 3 Wood U.m2), amrinone significantly reduced the pulmonary arteriolar resistance by 49%, total pulmonary resistance by 47% and pulmonary arteriolar/systemic vascular resistance ratio by 45% and increased the heart rate by 15%. CONCLUSIONS: In children with a cardiac left to right shunt, amrinone 1) appears to have selective vasodilator effects depending on the pulmonary artery pressure and resistance, 2) has a beneficial hemodynamic effect in children with normal pulmonary artery pressure and resistance, and 3) may have a role in the treatment of patients with pulmonary artery hypertension without causing systemic hypotension.

Amrinone↗
PubMed2000

Amrinone preconditioning in the isolated perfused rabbit heart.

BACKGROUND: Ischemic preconditioning (IPC) reduces infarct size in experimental preparations. IPC, however, is not without detrimental effects. We studied amrinone as a possible alternative to IPC. METHODS: Isolated perfused rabbit hearts were given a 5-minute infusion of 10 micromol/L amrinone followed by a 5-minute washout (n = 6). The anterior descending artery was then occluded for 1 hour and reperfused for 1 hour. Six hearts underwent IPC, with two episodes of 5-minute global ischemia followed by 5-minute reperfusion before LAD occlusion; eight control hearts received no preconditioning. Left ventricular pressure and ischemic zone epicardial monophasic action potentials were continuously monitored. RESULTS: IPC but not amrinone reduced peak pressure before anterior descending artery occlusion. Peak pressure fell significantly during ischemia and reperfusion in all hearts. End diastolic pressure rose significantly during reperfusion in control and IPC hearts but not in amrinone hearts. Action potentials shortened during ischemia in all hearts. They returned to preocclusion values in control hearts but lasted beyond preocclusion values in IPC and amrinone hearts. Both the incidences of ventricular fibrillation and infarct size were significantly reduced in amrinone hearts but not in IPC hearts. CONCLUSIONS: Amrinone is not only a useful inotropic agent but is also a superior preconditioning agent when compared to IPC.

Action Potentials↗
PubMed1997

Effect of the phosphodiesterase III inhibitor amrinone on cytokine and nitric oxide production in immunostimulated J774.1 macrophages.

The level of intracellular cyclic nucleotides is a regulatory factor in a variety of immune processes. Increases in intracellular cyclic AMP (cAMP) and/or cyclic GMP (cGMP) concentration by the inhibition of phosphodiesterase have been shown to modulate the inflammatory response. Amrinone is a clinically used positive inotropic agent which elevates intracellular cAMP and cGMP levels by selective inhibition of the phosphodiesterase III isoenzyme. In the current study, we investigated the effect of various concentrations (1-300 microM) of amrinone on lipopolysaccharide-induced production of pro- and anti-inflammatory cytokines and of nitric oxide (NO) in vitro. In cultured murine J774.1 macrophages, 1 ng/ml-10 microg/ml of lipopolysaccharide from Escherichia coli O55:B5 induced production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10, and nitrite (breakdown product of NO). Pretreatment of cells with amrinone caused a dose-dependent suppression of TNF-alpha production in the concentration range of 1-100 microM. Furthermore, this drug suppressed NO production in the range of 30-300 microM. Similarly to the results in the J774.1 cells, amrinone also inhibited TNF-alpha and NO production in the range of 10-100 microM in primary rat peritoneal macrophages. At 300 microM, but not at lower concentrations, amrinone inhibited interleukin-10 production in lipopolysaccharide-treated J774.1 macrophages. Pretreatment of the macrophages with 100 and 300 microM amrinone increased the lipopolysaccharide-elicited translocation of nuclear factor-kappa B. Taken together, our results indicate that the phosphodiesterase III inhibitor amrinone modulates the activation/production of many pro- and anti-inflammatory factors in endotoxin-stimulated cells. It remains to be further investigated how such immunomodulatory effects contribute to the clinical profile of the agent.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Effects of amrinone, a phosphodiesterase inhibitor, on right ventricular/arterial coupling immediately after cardiac operations.

OBJECTIVE: Amrinone, a selective phosphodiesterase III inhibitor, is reported to have a potent inotropic effect on the left ventricle, but the effects of this drug on right ventricular contractility in the clinical setting are unknown. The concept of ventricular/arterial coupling was applied to investigate the effects of amrinone on right ventricular contractility and afterload with transesophageal echocardiography. METHODS AND RESULTS: The study was performed in the intensive care unit with 11 patients who had undergone cardiac operations. Right ventricular cross-sectional area was measured with transesophageal echocardiography equipped with a capability of automated border detection as a surrogate for right ventricular volume. Multiple pressure-area loops were obtained by reducing preload to measure end-systolic elastance and effective arterial elastance. External work and pressure-volume area were also measured to calculate the efficiency of energy transfer from pressure-volume area to external work. Nitroprusside (0.3 to 0.5 microg x kg(-1) x min(-1)) and amrinone (1 mg x kg(-1) intravenously followed by 10 microg x kg(-1) x min(-1)) were administered. With nitroprusside infusion, end-systolic elastance and effective arterial elastance remained unchanged (end-systolic elastance, 4.73 +/- 2.18 mm Hg/cm2 to 4.65 +/- 2.09 mm Hg/cm2; effective arterial elastance, 8.05 +/- 3.84 mm Hg/cm2 to 7.70 +/- 3.64 mm Hg/cm2). In contrast, amrinone reduced afterload (effective arterial elastance, 8.82 +/- 3.99 mm Hg/cm2 to 7.05 +/- 4.01 mm Hg/cm2, p = 0.004) and enhanced contractility (end-systolic elastance, 4.47 +/- 1.79 mm Hg/cm2 to 6.56 +/- 2.22 mm Hg/cm2, p = 0.007). Consequently, amrinone decreased the ventricular/arterial coupling ratio (effective arterial elastance/end-systolic elastance, 2.40 +/- 1.45 to 1.16 +/- 0.63, p = 0.009) and improved the efficiency of energy transfer (external work/pressure-volume area, 0.44 +/- 0.15 to 0.54 +/- 0.15, p = 0.013). CONCLUSIONS: Right ventricular pressure-area relations obtained with transesophageal echocardiography could successfully separate the simultaneous change in right ventricular systolic mechanics and afterload caused by amrinone. Amrinone caused enhancement of right ventricular contractility and afterload reduction.

Adult↗
PubMed1997

Amrinone versus dopamine-nitroglycerin after reconstructive surgery for complete atrioventricular septal defect.

OBJECTIVES: To compare the effectiveness and safety of amrinone and a combination of dopamine and nitroglycerin in infants after reconstructive surgery for congenital heart disease. DESIGN: A prospective, randomized, double-blind study. SETTING: Pediatric intensive care unit in a university hospital. PARTICIPANTS: Thirty-two infants with complete atrioventricular septal defect. INTERVENTIONS: Amrinone loading dose, 2 mg/kg, followed by a maintenance infusion, 7.5 micrograms/kg/min, was given to 17 infants before separation from cardiopulmonary bypass. The remaining 15 patients received a combination of dopamine, 5 micrograms/kg/min, and nitroglycerin, 1 microgram/kg/min. 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 (2.5 +/- 0.7 L/min/m2) compared with the dopamine-nitroglycerin group (2.0 +/- 0.6 L/min/m2, mean +/- SD). The pulmonary blood flow index in the amrinone group was higher (2.9 +/- 0.6 L/min/m2) than in the dopamine-nitroglycerin group (2.2 +/- 0.6 L/min/m2); no significant difference was noted in the mean pulmonary artery pressure. The oxygen extraction ratio was higher in the dopamine-nitroglycerin group (0.41 +/- 0.07) compared with the amrinone group (0.34 +/- 0.08). Despite lower platelet counts in the amrinone group, no hemorrhagic complications were seen in any patient. CONCLUSIONS: With this dosage regimen, amrinone provides a higher cardiac output, more favorable oxygen dynamics, and lower pulmonary vascular resistance than dopamine and nitroglycerin.

Amrinone↗
PubMed1999

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.

Adrenergic Agonists↗
PubMed1996

The effects of amrinone and glucagon on verapamil-induced cardiovascular toxicity in anaesthetized rats.

The goal of this study was to compare the effects of glucagon and amrinone on mean arterial pressure (MAP) and heart rate, when used alone and in combination, in an anaesthetized rat model of verapamil toxicity. Rats were anaesthetized and the carotid artery was cannulated for MAP and heart rate measurements. Jugular and femoral veins were cannulated for drug administration. After verapamil infusion (15 mg/kg/h), control animals were given normal saline solution and the other groups received amrinone (0.1 or 0.2 mg/kg/min), glucagon (0.3 mg/kg bolus followed by 0.1 or 0.2 mg/ kg/min infusion), glucagon plus amrinone (0.1 mg/kg/min and 0.1 mg/kg/min respectively) or glucagon plus amrinone (0.2 mg/kg/min and 0.1 mg/kg/min respectively). Glucagon (0.2 mg/kg/min) significantly increased MAP when compared to the control group (P < 0.01). The combination of glucagon and amrinone did not produce a synergistic effect for the recovery of MAP. Furthermore, this combination masked the positive effects of glucagon (0.2 mg/kg/min) on MAP. Glucagon (0.2 mg/kg/min) increased the heart rates compared with those of the control group (P < 0.05). Additionally, amrinone (0.1 mg/kg/min) plus glucagon (0.1 mg/kg/min) increased the heart rates (P < 0.05). Finally, glucagon dose dependently recovered MAP. While amrinone depressed MAP in combination with glucagon, it did not alter the positive chronotropic effect of high dose glucagon.

Amrinone↗
PubMed2000

Disaggregatory effects of prostaglandin E1, amrinone and milrinone on platelet aggregation in human whole blood.

Prostaglandin E1 (PGE1), amrinone and milrinone not only inhibit platelet aggregation, but also potentially induce disaggregation. We examined the disaggregatory effects of PGE1, amrinone and milrinone on platelet aggregation, and measured the platelet cyclic adenosine monophosphate (cAMP) levels using a standard radioimmunoassay. Platelet aggregation was induced by 10 microM adenosine diphosphate (ADP) or 0.625 microg/ml collagen that induces a secondary aggregation, and measured by whole blood aggregometry. PGE1 (0.7-10.0 microM), amrinone (106.8-801.3 microM), or milrinone (9.5-190.0 microM) was added when aggregation reached 5 mohm of impedance, and the percentage of disaggregation was measured 5 min after initiating disaggregation. Disaggregatory effects were also examined using a light transmission aggregometer and gel-filtered platelets. In platelet aggregation induced by ADP, the drug concentrations required to cause 50% disaggregation (EC50) were PGE1; 3.1+/-1.2 microM, amrinone; 313.1+/-128.8 microM, milrinone; 57.1+/-20.8 microM. In platelet aggregation induced by collagen, the maximum disaggregation percentages were 15.6+/-5.0% for 10 microM PGE1, 7.8+/-2.4% for 801.3 microM amrinone, and 5.9+/-2.3% for 190.0 microM milrinone. The EC50 concentrations of platelet cAMP that caused 50% disaggregation in ADP-induced platelet aggregation were 67+/-13 pmoles/10(8) platelets for PGE1, 54+/-12 pmoles/10(8) platelets for amrinone, and 52+/-12 pmoles/10(8) platelets for milrinone. In gel-filtered platelets, the percentages of disaggregation in ADP- or collagen-induced platelet aggregation were 33.1+/-5.2% or 11.2+/-3.1% for PGE1 (10 microM), 22.3+/-4.1% or 15.2+/-3.2% for amrinone (801.3 microM), and 23.5+/-4.3% or 14.6+/-3.5% for milrinone (190.0 microM).

Adenosine Diphosphate↗
PubMed2001

Amrinone can accelerate the cooling rate of core temperature during deliberate mild hypothermia for neurosurgical procedures.

We investigated the effects of i.v. amrinone on intraoperative changes of core temperature during deliberate mild hypothermia for neurosurgery. The patients in a control group (n=10) did not receive amrinone and patients in the amrinone group (n=10) received amrinone 5 microg kg(-1) min(-1) after a loading dose of 1.0 mg kg(-1). Anaesthesia was maintained with nitrous oxide in oxygen, propofol and fentanyl. After the induction of anaesthesia, patients were cooled and tympanic membrane temperature was maintained at 34.5 degrees C. After completion of the main surgical procedures, patients were rewarmed in the operating room. Tympanic membrane temperatures between 30 and 90 min after cooling were significantly lower in the amrinone group than in the control group. During cooling, the times taken to cool to 35 degrees C and to the lowest temperature were significantly shorter in the amrinone group than in the control group. These results suggest that i.v. amrinone can accelerate the cooling rate of core temperature during deliberate mild hypothermia for neurosurgical procedures.

Amrinone↗
PubMed1984

Inotropic and vasodilator effects of amrinone on isolated human tissue.

The effects of amrinone on human umbilical artery and human myocardium were studied. Amrinone produced dose related increases in tension, dT/dtmax and dT/dtmin in myocardium from patients who were NYHA grade I (n = 1) and II (n = 4). The responses to amrinone of these tissues were similar to the response seen in normal guinea-pig myocardium (n = 34). The drug had no inotropic effect on tissue from NYHA grade III patients (n = 5). The inotropic response of the tissues to amrinone was inversely related to length of history and severity of heart failure in the patients from whom the tissues were obtained. Amrinone caused dose related relaxation of the human umbilical artery. The vasodilator properties, but not the positive inotropic effects of amrinone were detectable at concentrations of the drug obtained during oral therapy (0.4 to 4.0 micrograms X ml-1). These findings support the view that in patients with congestive cardiac failure amrinone acts by vasodilatation with no clinically important positive inotropic effect.

Aminopyridines↗
PubMed1993

Amrinone attenuates airway constriction during halothane anesthesia.

BACKGROUND: Phosphodiesterase (PDE) inhibitors should, in theory, be useful in patients with both cardiac and reactive airway disease who require anesthesia. The effects of the PDE inhibitor, amrinone, on the release of endogenous catecholamines and on airway reactivity to aerosol methacholine challenge were evaluated during thiopental/fentanyl and halothane anesthesia in five mongrel dogs. METHODS: Responses to methacholine aerosol challenge (0.03, 0.075, 0.15, 0.30, 0.75, and 3.0 mg/ml) were measured during four conditions: thiopental/fentanyl anesthesia, thiopental/fentanyl anesthesia with amrinone infusion, halothane anesthesia, and halothane anesthesia with amrinone infusion. Increase in pulmonary resistance (RL) and decreases in dynamic compliances (Cdyn) were calculated for each methacholine dose. Plasma epinephrine and norepinephrine concentrations were measured during thiopental/fentanyl anesthesia with amrinone infusion. RESULTS: Before aerosol challenge, baseline RL and Cdyn did not differ in the four groups. Amrinone significantly attenuated the pulmonary response to methacholine during both thiopental/fentanyl and halothane anesthesia. Plasma catecholamine concentrations did not increase during amrinone infusion. CONCLUSIONS: Amrinone attenuates methacholine-induced airway responses even during halothane anesthesia. These data indicate that isozyme-selective PDE inhibitors hold promise for the perioperative treatment of bronchospasm.

Amrinone↗
PubMed1989

Amrinone in neonates and infants after cardiac surgery.

Eighteen critically ill postoperative patients less than 1 yr of age were studied to determine the pharmacokinetics and adverse effects of amrinone. All patients had undergone cardiopulmonary bypass for repair of congenital heart lesions. Plasma samples were obtained every 12 h while patients were receiving amrinone to determine when steady state was achieved; samples were also obtained within 24 h after amrinone had been discontinued. Elimination half-life (T1/2), clearance, and volume of distribution were calculated from plasma amrinone concentrations, and the incidence of platelet transfusion was monitored. T1/2(22.2 vs. 6.8 h) and clearance (1.1 vs. 2.6 ml/min.kg), but not the volume of distribution (1.8 vs. 1.6 L/kg), differed significantly in patients less than 4 wk of age in comparison to patients greater than 4 wk of age. A negative correlation between T1/2 and age (r = -.79) was observed. Platelets were administered no more frequently in study patients than in a similar group that did not receive amrinone. To achieve the plasma concentration of amrinone that is therapeutic in adults, current dosage recommendations are inadequate in neonates and infants. Infants should receive an initial iv amrinone bolus of 3.0 to 4.5 mg/kg in divided doses followed by a continuous infusion of 10 micrograms/kg.min, while neonates should receive a similar bolus followed by a continuous infusion of 3 to 5 micrograms/kg.min.

Amrinone↗
PubMed1994

Thermogenic effect of amrinone in healthy men.

OBJECTIVES: The thermogenic effect of amrinone is unknown and its utilization in patients with severe cardiac failure could potentially increase oxygen requirements and therefore aggravate oxygen debt. Consequently, the present study was undertaken to assess the thermogenic response to amrinone at three different plasma concentrations under controlled conditions and to analyze amrinone's effects on various biochemical variables. DESIGN: A prospective, unblinded, controlled study. The initial control period was followed by three sequential, experimental treatments. SUBJECTS: Ten young, healthy, male volunteers with normal body weight. INTERVENTIONS: Three experimental periods. Amrinone was administered intravenously in progressive doses: a) 0.5 mg/kg followed by 5 micrograms/kg/min; b) 0.5 mg/kg followed by 10 micrograms/kg/min; and c) 1.0 mg/kg followed by 10 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption (VO2) and CO2 production were continuously measured by means of a computerized indirect calorimeter. At the highest dose, amrinone produced a slight and significant (p < .01) increase in VO2 and in resting metabolic rate (+4.5% and +3.7%, respectively), while no change in CO2 production or in respiratory quotient occurred throughout the study. At the medium and high doses, amrinone increased plasma free fatty acid concentrations by 38% and 53%, respectively (p < .05). No variation in plasma glucose, lactate, insulin, norepinephrine, or epinephrine concentrations was observed during the study. CONCLUSIONS: Amrinone administered intravenously at therapeutic doses has minimal thermogenic and metabolic effects in humans without cardiac failure.

Adult↗
PubMedDate not supplied

Electrical and mechanical effects of amrinone on isolated guinea pig ventricular muscle.

The electromechanical effects of amrinone on isolated guinea pig papillary muscle were studied at various driving frequencies and under the influence of several antagonists and a low calcium medium. Amrinone (3 X 10(-5)-2 X 10(-3)M) caused a positive inotropic effect on preparations driven at 1.0 Hz in a concentration-dependent manner. When the preparations were driven at a frequency lower than 0.5 Hz, the positive inotropic effect of the drug was markedly attenuated. Amrinone caused a significant prolongation in action potential duration at an early repolarization phase--but not at a late repolarization phase--without affecting any other parameters of action potential. These effects of amrinone were not blocked by a beta-adrenoceptor antagonist or tetrodotoxin, but were inhibited by treatment with verapamil (5 X 10(-6)M) or a low calcium medium (0.1 or 0.3 mM). In papillary muscles depolarized by 30 mM [K+]o, amrinone enhanced the slow action potentials. In voltage clamp experiments using a single sucrose-gap method, amrinone (6 X 10(-4)M) caused a marked increase in the peak amplitude of the slow inward current, while it did not affect the net outward current. The results suggest that the slow calcium inward current may play a predominant role in the positive inotropic effect of amrinone.

Action Potentials↗
PubMed1991

Amrinone reduces pulmonary vascular resistance elevated by U46619 in isolated perfused lungs.

The effects of amrinone on pulmonary vascular resistance (PVR) were studied in an isolated, perfused rabbit lung model where all the major determinants of PVR were controlled. In this preparation, the alveolar oxygen and carbon dioxide tensions, vascular pH and vascular oxygen and carbon dioxide tensions, and zonal conditions of the lung and phasic variations of pulmonary artery pressures could be precisely measured and controlled. Measurements of PVR were made by a complete determination of the pulmonary pressure-flow curve and determination of the PVR under identical flow conditions for all studies. This approach allowed a more precise determination of the primary effects of amrinone on normal and elevated PVR than has been previously possible. We found that amrinone in final concentrations of either 4 or 8 micrograms/ml had no effect on basal PVR and no effect on lung water weight to dry ratios. When PVR was elevated by the addition of the thromboxane A2 mimetic U46619, amrinone reduced the PVR by 27% at a final concentration of 4 micrograms/ml and by 74% at a final concentration of 8 micrograms/ml. We conclude that in the doses tested, amrinone has no effects on basal PVR but is able to reduce elevated PVR in a dose-dependent manner. These results are the first to demonstrate clearly that amrinone has the ability to reduce elevated pulmonary vascular tone through a direct mechanism and not through secondary effects on other determinants of PVR such as left atrial pressure (Pla), increased cardiac output with resultant vascular recruitment, or increases in mixed venous oxygen tension. The possible implications for the clinical use of amrinone in situations of elevated PVR are discussed.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Clinical use of amrinone (a selective phosphodiesterase III inhibitor) in reconstructive surgery.

Amrinone is a selective phosphodiesterase III inhibitor that increases cyclic adenosine monophosphate by preventing its breakdown. It is effective in the treatment of congestive heart failure because of its ability to increase myocardial contractility and vascular smooth muscle relaxation. This study was designed to clarify the potential efficacy of amrinone in plastic surgery by clinically assessing its ability to enhance flap blood flow after reconstructive surgery and relieve intraoperative vasospasm. Its effects were compared with those of prostaglandin E1 and lidocaine, which are widely approved agents for improving the hemodynamics of flaps. In the first clinical study, the effects on flap blood flow after flap transfers were investigated. Twenty-six patients underwent reconstructive surgery with vascularized free or pedicled flaps. Blood flow was measured before and 60 minutes after intravenous infusion of lactated Ringer solution (control), amrinone (10 microg/kg/min), or prostaglandin E1 (10 ng/kg/min) using a laser Doppler flowmeter. In the second study, the effects on relief of vasospasm during operation were evaluated. The blood flow of 28 island flaps was measured by laser Doppler flowmetry immediately after flap elevation and 10 minutes after topical application of saline (control), amrinone (5 mg/ml), or lidocaine (10%) to the pedicle in an attempt to resolve the vasospasm. In both clinical studies, the effects of amrinone were statistically no less than those of prostaglandin E1 and lidocaine. The results show that amrinone positively influences the microcirculatory blood flow of transferred flaps and relieves intraoperative vasospasm in clinical cases. The present study suggests that amrinone could be useful for postoperative and intraoperative care in reconstructive surgery.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Interaction of amrinone with endogenous adenosine in guinea-pig atria.

In spontaneously beating atria from reserpine-treated guinea-pigs, amrinone (10 microM to 2 mM) induced a positive inotropic and chronotropic effect that was preceded by a transient reduction in contractile force and in frequency. Both the positive and negative effects were concentration-dependent. The inotropic action of amrinone was antagonized by low concentrations of 8-phenyltheophylline that compete with adenosine at R-receptors on plasma membrane without significantly influencing phosphodiesterase activity. Cumulative concentrations of amrinone (1 mM) antagonized the reduction of rate of contraction and amplitude induced by dipyridamole 1 microM in spontaneously beating atria and restored the maximum contractile effect reached in the absence of dipyridamole. In spontaneously beating preparations incubated in the presence of adenosine deaminase (1 u ml-1), amrinone lost its positive effects on the atria and only reduction of rate and contractile force was evident. Both effects were antagonized by scopolamine 1 mM thus indicating their cholinergic nature. Adenosine at 0.1 microM and 0.5 microM significantly inhibited the inotropic effect induced by amrinone (0.03 to 3 mM) and the concentration-effect curves of amrinone obtained in the absence and presence of adenosine clearly indicate a competitive antagonism between the two drugs. Thus the contractile activity of amrinone in spontaneously beating atria from reserpine-treated guinea-pigs originates from a displacement of adenosine from its R-receptor sites in the cardiac cell.

Adenosine↗
PubMed1995

A randomized comparison of intravenous amrinone versus dobutamine in older patients with decompensated congestive heart failure.

OBJECTIVE: To compare the hemodynamic effects of amrinone and dobutamine in patients 75 years of age or older who have severe congestive heart failure requiring invasive hemodynamic monitoring and inotropic support. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: Coronary care unit of a university teaching hospital. PARTICIPANTS: Fourteen patients > or = 75 years of age (mean 80.3 +/- 5.7 years) with refractory New York Heart Association class IV congestive heart failure. All patients had a cardiac index < 2.5 L/min/M2 (mean 1.8 +/- 0.3 L/min/M2), pulmonary capillary wedge pressure > or = 18 mm Hg (mean 26 +/- 10 mm Hg), and left ventricular ejection fraction < 40% (mean 26 +/- 10%). INTERVENTION: Patients were randomly assigned to treatment with 2-hour infusions of amrinone (n = 7) or dobutamine (n = 7) at fixed dosages of 5 and 10 micrograms/kg/min. MEASUREMENTS: Complete hemodynamic data were obtained at baseline and after each 2-hour medication infusion. Transthoracic two-dimensional echocardiography was performed at baseline and after the 10 micrograms/kg/min medication dose. The primary analysis compared the effects of the two drugs on cardiac index and stroke volume index at each of the two dosages. RESULTS: Both amrinone and dobutamine had salutary hemodynamic effects, as indicated by improvements in cardiac index, stroke volume index, pulmonary capillary wedge pressure, and systemic vascular resistance (all P < .05 except effect of amrinone on stroke index and wedge pressure). Although the overall hemodynamic effects of amrinone and dobutamine were similar, stroke volume index was higher with dobutamine at the 10 micrograms/kg/min dose (35 +/- 7 ml/M2 vs 26 +/- 6 mL/M2; P = .045). Two dobutamine patients were withdrawn from the study after the 5 micrograms/kg/min dose due to adverse effects (tachycardia, increased ventricular ectopy). One additional patient in each group was noted to have ventricular arrhythmias not requiring termination of the protocol. CONCLUSIONS: Both amrinone and dobutamine are efficacious in improving hemodynamics in older patients with severe congestive heart failure caused by left ventricular contractile dysfunction. Despite the effect of aging on beta-adrenergic responsiveness, dobutamine is at least as effective as amrinone but may be associated with a higher incidence of arrhythmic side effects.

Aged↗