Amrinone Infusion Research Articles

Sevoflurane in an infant with dilated cardiomyopathy due to myocarditis and hypocalcaemia.

Sir, A 9-month-old infant with dilated cardiomyopathy (DCM) due to myocarditis and hypocalcaemia was posted for cataract extraction in both eyes at 1-week interval under general anaesthesia. The child was weighing 4.5 kg with microcephaly, microphthalmos, microstomia, micrognathia, deep set eyes, diffuse grade 1 Ashworth spasticity of both lower limbs, hepatosplenomegaly and global developmental delay. At 6 months of age, the infant was admitted to hospital for congestive cardiac failure for 15 days and was managed conservatively with calcium, angiotensin converting enzyme (ACE) inhibitors and carnitine. Blood investigations at the time of hospital admission showed raised total leucocyte count and erythrocyte sedimentation rate, serum potassium − 5.2 mmol/l, albumin globulin ratio 0.73, serum calcium 8.5 mg/dl, ionised calcium 3.94 mg/dl and normal thyroid profile., Immunoglobulin G for herpes simplex virus 1, 2 and cytomegalovirus were strongly positive indicating congenital infection and had normal karyotype (46XY) and abdominal ultrasound. Chest X-ray showed cardiomegaly with increased pulmonary markings [Figure 1]. Echocardiography showed DCM with an ejection fraction of 30% with patent foramen ovale and no pulmonary arterial hypertension. The infant was reviewed after a month with repeat echocardiography which showed same changes. Figure 1 Chest X-ray showing cardiomegaly and increased pulmonary vasculture Following standard fasting protocol, all drugs were continued on the morning of surgery. Paediatric cardiologist was called as standby for intraoperative pacemaker insertion if required. The infant was induced with sevoflurane in a graded manner via face mask with oxygen, and an intravenous line was secured. Intravenous glycopyrrolate 0.03 mg, fentanyl 5 μg was administered. The infant could be intubated with 4.0 mm uncuffed endotracheal tube under sevoflurane and propofol (2 mg/kg) at 3 min after induction. Arterial line was secured and vitals (heart rate, saturation, temperature, invasive blood pressure and EtCO2) were monitored continuously. Anaesthesia was maintained with oxygen, nitrous oxide and sevoflurane with 3 volume % concentration with spontaneous ventilation. Crystalloid was administered as per Holliday-Segar recommendations. The procedure took 90 min. Patient was stable throughout the procedure and trachea was extubated after withdrawing sevoflurane. The infant was monitored for 24 h in the paediatric intensive care unit and discharged on second post-operative day. The infant was posted for other eye procedure a week later. Same precautions and procedures were followed and was discharged successfully on post-operative day two. DCM with an incidence of 1.13 cases/100,000 children[1] is characterised by dilatation and impaired contraction of the left ventricle or both ventricles. It may be idiopathic, familial/genetic, viral and/or immune, toxic or related to endocrine disease and malnutrition. It can present with progressive heart failure, arrhythmias, thromboembolism and sudden death.[2] There are very few clinical signs until DCM is severe. In smaller children, any history of a cough, decreased effort tolerance, poor feeding, failure to thrive, syncopal episodes or chest pain should result in a thorough examination looking for cardiomegaly and clinical signs of cardiac failure. Often there is associated mitral valve regurgitation, tricuspid valve regurgitation or both.[3] Main issues of anaesthetic concerns were difficult intubation due to microcephaly, microstomia, short neck and spasticity, associated myopathy, dehydration, the risk of embolism and recovery. The pre-operative assessment included a mandatory echocardiogram to determine ventricular function. Potassium level was evaluated as these patients may be receiving diuretics or digoxin and hypokalaemia is corrected before the operation. ACE inhibitors were continued on the day of surgery despite the risk of intraoperative hypotension[4] after consultation with paediatric cardiologist. Dobutamine and amrinone infusion were prepared as inotropic agents to manage hypotension.[5] Increase in peripheral vascular resistance (PVR) due to hypercarbia or hypoxia, and decrease in the venous return due to high airway pressures were avoided as elevated PVR in the presence of a low cardiac output in these patients may cause rapid haemodynamic deterioration. In conclusion, better pre-operative assessment should be followed by formulation of anaesthetic plans keeping in mind the cardiac status, a continuation of ACE inhibitors, anticipating difficult intubation, maintaining euvolaemia and avoiding cardio-depressant drugs. Sevoflurane may be safely used in in infants with DCM as it causes less haemodynamic alterations and it could also help in tracheal intubation without muscle relaxant. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Mechanisms of increased right and left ventricular oxygen uptake during inotropic stimulation

AimsFew studies have investigated oxygen supply/demand relations in right ventricle (RV). The current study compared changes in myocardial oxygen uptake (MVO2) and its determinants, myocardial blood flow (MBF) and oxygen extraction (EO2), in RV and left ventricle (LV) during stimulation with inotropic drugs. Main methodsTwenty-one anesthetized dogs were studied. MBF was measured with radioactive microspheres. A-VO2 difference was determined separately for RV and LV, and used to calculate MVO2 (Fick equation) and EO2. Responses to iv. infusions of isoproterenol (0.1μg/kg/min), dobutamine (5μg/kg/min), and amrinone (1mg/kg+10μg/kg/min) were assessed. Key findingsBaseline MVO2 in RV was 50–60% of that in LV. The inotropes increased MVO2 in both RV and LV (range 32–63%; P<0.05). With isoproterenol, the increased MVO2 in the RV was due to increases in both MBF and EO2, whereas in LV it was due only to increases in MBF. With dobutamine and amrinone, the increased MVO2 in RV was due to increased MBF while EO2 was constant (dobutamine) or decreased (amrinone), and that in the LV was due to increased MBF while EO2 decreased. SignificanceRV possesses EO2 reserve that contributed to increased MVO2 during isoproterenol infusion, whereas LV depended on increased MBF alone. Because dobutamine and amrinone caused direct coronary vasodilation, i.e., “luxuriant perfusion,” it was not necessary to recruit the EO2 reserve. Thus, it remained available to meet further increases in MVO2 or to maintain MVO2 in the face of reductions in MBF.

The role of phosphodiesterase 3 in endotoxin-induced acute kidney injury

BackgroundAcute kidney injury frequently accompanies sepsis. Endotoxin is known to reduce tissue levels of cAMP and low levels of cAMP have been associated with renal injury. We, therefore, hypothesized that endotoxin induced renal injury by activating phosphodiesterase 3 (PDE3) which metabolizes cAMP and that amrinone an inhibitor of PDE3 would prevent the renal injury.MethodsAnimals were divided into three groups (n = 7/group): 1) Control (0.9% NaCl infusion without LPS); 2) LPS (0.9% NaCl infusion with LPS); 3) Amrinone+LPS (Amrinone infusion with LPS). Either lipopolysaccharide (LPS) or vehicle was injected via the jugular vein and the rats followed for 3 hours. We explored the expression of PDE3 isoenzymes and the concentrations of cAMP in the tissue.ResultsThe PDE3B gene but not PDE3A was upregulated in the kidney of LPS group. Immunohistochemistry also showed that PDE3B was expressed in the distal tubule in the controls and LPS caused PDE3B expression in the proximal as well. However, PDE3A was not expressed in the kidney either in the control or LPS treated groups. Tissue level of cAMP was decreased after LPS and was associated with an increase in blood urea nitrogen, creatinine, ultrastructural proximal tubular changes, and expression of inducible nitric oxide synthase (iNOS) in the endotoxemic kidney. In septic animals the phosphodiesterase 3 inhibitor, amrinone, preserved the tissue cAMP level, renal structural changes, and attenuated the increased blood urea nitrogen, creatinine, and iNOS expression in the kidney.ConclusionThese findings suggest a significant role for PDE3B as an important mediator of LPS-induced acute kidney injury.

Natriuretic Peptide System Gene Variants Are Associated with Ventricular Dysfunction after Coronary Artery Bypass Grafting

Ventricular dysfunction (VnD) after primary coronary artery bypass grafting is associated with increased hospital stay and mortality. Natriuretic peptides have compensatory vasodilatory, natriuretic, and paracrine influences on myocardial failure and ischemia. The authors hypothesized that natriuretic peptide system gene variants independently predict risk of VnD after primary coronary artery bypass grafting. A total of 1,164 patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass at two institutions were prospectively enrolled. After prospectively defined exclusions, 697 patients of European descent (76 with VnD) were analyzed. VnD was defined as need for at least 2 new inotropes and/or new mechanical ventricular support after coronary artery bypass grafting. A total of 139 haplotype-tagging single nucleotide polymorphisms (SNPs) within 7 genes (NPPA, NPPB, NPPC, NPR1, NPR2, NPR3, CORIN) were genotyped. SNPs univariately associated with VnD were entered into logistic regression models adjusting for clinical covariates predictive of VnD. To control for multiple comparisons, permutation analyses were conducted for all SNP associations. After adjusting for clinical covariates and multiple comparisons within each gene, seven NPPA/NPPB SNPs (rs632793, rs6668352, rs549596, rs198388, rs198389, rs6676300, rs1009592) were associated with decreased risk of postoperative VnD (additive model; odds ratios 0.44-0.55; P = 0.010- 0.036) and four NPR3 SNPs (rs700923, rs16890196, rs765199, rs700926) were associated with increased risk of postoperative VnD (recessive model; odds ratios 3.89-4.28; P = 0.007-0.034). Genetic variation within the NPPA/NPPB and NPR3 genes is associated with risk of VnD after primary coronary artery bypass grafting. Knowledge of such genotypic predictors may result in better understanding of the molecular mechanisms underlying postoperative VnD.

The Effect of Amrinone on Liver Regeneration in Experimental Hepatic Resection Model 1

The phosphodiesterase inhibitors (PDEIs) have been proposed to improve hepatic reperfusion injury and hepatosplanchnic circulation, but the effects of these agents on liver regeneration have not been investigated thoroughly. The aim of this study was to investigate the effect of amrinone, a PDEI, on liver regeneration in rats. Sixty rats were divided into two groups, control and amrinone. Each group was then divided into three groups (n=10). An infusion of amrinone to the study group and of 0.9% NaCl to the control group was performed. Seventy percent liver resection was performed to the rats during the first hour of infusion. The infusion was maintained for 17 h after resection. A total of 18 h infusion was performed. Rats were allowed to survive for 24, 48, and 72 h, and then they were sacrificed. Biochemical, morphological, hematological, and histopathologic measurements and assessments were performed. There were statistically significant differences between the amrinone and control groups in alkaline phosphatase and relative liver weights at 24, 48, and 72 h (P<0.05). There also were statistically significant differences between the groups in AST, bilirubin, and albumine levels at 24 h, ALT and prothrombine time levels at 48 h, and aspartate aminotransferase and alanine aminotransferase levels at 72 h (P<0.05). Hepatic ATP levels, mitotic index, and proliferating cell nuclear antigen labeling index were significantly higher in amrinone group compared with control group at all three time intervals (P<0.05). Amrinone improves both morphological and functional liver regeneration after liver resection.

Intraoperative insulin therapy does not reduce the need for inotropic or antiarrhythmic therapy after cardiopulmonary bypass

Objective: To determine whether attempted glucose control through intraoperative insulin therapy reduces the need for inotropic or antiarrhythmic therapy after cardiopulmonary bypass (CPB). Design:Post hoc analysis of a randomized, masked clinical trial of insulin therapy for prevention of neurobehavioral deficits. Setting: Single university hospital. Participants: Nondiabetic patients undergoing elective coronary artery bypass graft surgery (n = 381). Interventions: Patients received either insulin infusions in an attempt to maintain blood glucose at 80 to 120 mg/dL (n = 188) or placebo (saline; n = 193). Inotropic therapy was defined as the initiation of vasoactive support with epinephrine or amrinone infusions or mechanical support with the initiation of an intra-aortic balloon pump in the operating room or within 12 hours postoperatively. Antiarrhythmic therapy was defined as cardioversion, antiarrhythmic medications, or pacing. Measurements and Main Results: Of patients, 64 in the placebo group and 71 in the insulin group required inotropic support after CPB (p = not significant). The use of cardioversion (55 in placebo group v 61 in insulin group), antiarrhythmic medications (64 in placebo group v 76 in insulin group), and pacing (118 in placebo group v 117 in insulin group) was similar between groups. Inotropic drug support was associated with age >60 years, female gender, reduced preoperative ejection fraction, history of angina, and increased duration of CPB. Conclusion: Intraoperative insulin therapy did not reduce the use of inotropic or antiarrhythmic support after cardiac surgery with CPB. The lack of benefit may be due to the inability to prevent hyperglycemia during the physiologic stress of CPB or a tribute to the effectiveness of modern myocardial preservation techniques. Copyright 2002, Elsevier Science (USA). All rights reserved.

Adenosine and amrinone reverse felypressin-induced depression of myocardial tissue oxygen tension in dogs.

To determine whether continuous infusion of adenosine triphosphate (ATP), nitroglycerin (NTG) or amrinone (AM) would ameliorate the reductions in coronary blood flow (CBF) and myocardial oxygen tension (PmO2) induced by felypressin. Seven open-chest dogs were studied under urethane and alpha-chloralose anesthesia. Hemodynamic variables including heart rate (HR), systolic blood pressure, diastolic blood pressure (DBP), mean pulmonary artery pressure, pulmonary capillary wedge pressure, CBF (ultrasound flowmetry), PmO2(polarography) and cardiac output (thermodilution method) were recorded. Felypressin was infused in a loading dose of 6 mIU x kg(-1) for five minutes and then continued at 0.2 mIU x kg(-1) x min(-1). After 30 min felypressin infusion, each agent was administered for 15 min to evaluate hemodynamic changes. Infusions were 100 and 200 microg x kg(-1) x min(-1) for ATP, 2.5 and 5 microg x kg(-1) x min(-1) for NTG, and 10 and 20 microg x kg(-1) x min(-1) for AM. After felypressin DBP increased by 17 +/- 5 (mean +/- SD) %; CBF decreased by 49 +/- 9%; CI decreased by 40 +/- 13%; HR decreased by 29 +/- 11%; PmO2 in the inner layer decreased by 21 +/- 7%. The Cl and CBF returned to baseline afterATP 100 and 200 microg x kg(-1) x min(-1), AM 10 and 20 microg x kg(-1) x min(-1), but not after NTG. The PmO2 in the inner layer returned to the baseline value by any infusion except for NTG 5 microg x kg(-1) min(-1) Adenosine and amrinone, but not nitroglycerin reverses the adverse cardiovascular effects of felypressin.

Influence of amrinone on intestinal villus blood flow during endotoxemia

Purpose: The objective of this study was to determine the effects of a continuous infusion of the phosphodiesterase (PDE) inhibitor amrinone on mucosal villus blood flow in a normotensive model of endotoxemia. Materials and Methods: Twenty-four anesthetized and ventilated rats underwent laparotomy, and an ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed on a plexiglass stage with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without phosphodiesterase inhibitor pretreatment (LPS group); or infusion of LPS with amrinone pretreatment (40 μg/kg/min, start 30 minutes before LPS infusion) (amrinone group), or infusion of eqivalent volumes of NaCl 0.9% (control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = DA and mean erythrocyte velocity within the arterioles = VE) were measured 30 minutes before and at 0, 60, and 120 minutes after induction of endotoxemia. Mucosal villus blood flow was calculated from DA and VE.Results: In this normotensive endotoxemia model, MAP remained stable in the control and the LPS group but significantly decreased in the amrinone group. The endotoxin-induced decrease of VE and DA of central arterioles of mucosal villi could be attenuated and prevented, respectively. Thus, the endotoxin-induced decrease of mucosal villus blood flow was diminished but not fully restored by amrinone infusion. Conclusion: Our results indicate that amrinone during an early stage of sepsis is of limited value. It attenuates mucosal hypoperfusion but contributes to systemic hypotension. Copyright © 2000 by W.B. Saunders Company

Influence of Amrinone on Tissue Oxygenation of Jejunal Mucosa during Endotoxemia

The intestinal mucosa is the portion of the gut most susceptible to impaired perfusion and oxygen delivery. The phosphodiesterase (PDE) inhibitor amrinone has been proposed to improve oxygen delivery and tissue perfusion during sepsis. The objective of this study was to investigate the effects of amrinone on arterial oxygenation (Pao(2)) and tissue oxygenation (Ptio(2)) of jejunal mucosa during endotoxemia. Forty anesthetized and ventilated rats were laparotomized and a jejunal portion was exteriorized and fixed on a plexiglass stage. The jejunum was punctured and a Clark-type microcatheter Po(2) probe and a microthermocouple were placed on the mucosa to measure Ptio(2). The animals were randomly assigned to receive one of the four treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without amrinone pretreatment (LPS group); infusion of LPS with amrinone pretreatment (40 microg/kg/min, start 30 min before LPS infusion, amrinone + LPS group); no treatment with either amrinone or LPS (control group); treatment with amrinone without LPS infusion (amrinone group). Mean arterial pressure (MAP), heart rate (HR), Pao(2), and Ptio(2) were measured 30 min before and 0, 60, and 120 min after induction of endotoxemia. MAP remained stable in the control and LPS groups. In the amrinone + LPS group MAP decreased within the first 30 min of amrinone infusion and decreased further during endotoxemia. Pao(2) remained stable in the control group and decreased in the LPS group. This endotoxin-induced decrease in Pao(2) was attenuated in the amrinone + LPS group. The mucosal Ptio(2) decreased in the LPS group but remained stable in both the control and amrinone + LPS groups. Pretreatment with amrinone was able to diminish a decrease in Pao(2) during endotoxemia, indicating that pulmonary dysfunction was attenuated. Endotoxin-induced tissue hypoxia of the intestinal mucosa, however, could be fully prevented, indicating that an additional improvement in compromised tissue perfusion had occurred.

Hemodynamic effect of amrinone depends on pretreatment vascular resistance in patients with evolving congestive heart failure: correlation between vascular resistance and neurohormonal activity.

We investigated the hemodynamic effects of amrinone and assessed its effects on neurohormonal factors in 15 patients with evolving congestive heart failure with various origins. We serially determined the pulmonary and systemic vascular-resistance indices after amrinone infusion and examined the relation between changes in hemodynamic parameters and changes in concentrations of norepinephrine, atrial natriuretic peptide, angiotensin II, and endothelin-1 in the pulmonary capillary wedge region (PCWR) and in the peripheral veins. Amrinone significantly reduced pulmonary vascular-resistance index (PVRI; Wood x m2) in patients with high PVRI (> or =15) before the infusion, significantly reduced systemic vascular-resistance index (SVRI; Wood x m2) in patients with high SVRI (> or =50) before the infusion, and had little effect on vascular resistances in patients with low PVRI (<15) and low SVRI (<50). The reduction in PVRI was correlated with the reduction in the endothelin-1 level (r = 0.75) in the PCWR, and the reduction in SVRI with norepinephrine level (r = 0.70) in the peripheral veins. The angiotensin II level did not change throughout the study. These findings suggest that amrinone had selective hemodynamic effects on pulmonary and systemic circulations with neurohormonal effects, according to PVRI and SVRI before infusion.

The effects of dopamine, dobutamine and amrinone on mitochondrial function in cardiogenic shock.

The impairment of mitochondrial in non-infarcted myocardium under cardiogenic shock complicated by acute myocardial infarction was studied. We induced acute myocardial infarction in dogs by ligating the circumflex branch of the left coronary artery (LCX). On basis of left ventricular systolic pressure (LVPs) after 60 minutes, we divided the dogs into two groups: a group in which LVPs fell to below 70% of the pre-LCX ligation level, and a Control group in which LVPs remained more than 90%. The former group was further divided into four subgroups, depending on infusion of dopamine, dobutamine, amrinone or saline after 90 minutes. Mitochondria were prepared and mitochondrial respiratory activity determined. In the Saline group, hemodynamics became reduced to less than 70% of the preligation level after 120 minutes, however, in the Dopamine and Dobutamine groups, hemodynamics became restored to the preligation level. In the Amrinone group, LVPs decreased slightly, while cardiac output, LV Max. dp/dt and myocardial blood flow increased. In the Saline group, mitochondria in the non-infarcted myocardium functioned at a lower level of activity than that of the Control group. However, in the Dopamine, Dobutamine, and Amrinone groups, the mitochondria functioned at a higher level. Electron microscopy revealed mitochondrial damage in the Saline group only. The results indicate that an energy production disorder in the non-infarcted myocardium may have pathogenetic implications in cardiogenic shock associated with acute myocardial infarction, while dopamine, dobutamine, and amrinone improve mitochondrial function, and ultimately improve cardiac function.

Beneficial effects of amrinone in a patient with primary pulmonary hypertension and severe hypoxemia

A 31-year-old man was admitted to the ICU with a diagnosis of primary pulmonary hypertension and severe hypoxemia caused by hemoptysis. Examinations revealed 112/56mmHg of systemic artery pressure, 113/54mmHg of pulmonary artery pressure and a PaO2/FIO2 ratio of 87. Continuous intravenous infusion of PGE1 and dopamine worsened the pulmonary hypertension. Continuous intravenous infusion of PGE1 and amrinone improved pulmonary hypertension (75/53mmHg; vs. systemic artery pressure 110/70mmHg) and raised the PaO2/ FIO2 ratio to 300.The patient died of massive hemoptysis several days later, however amrinone may be an effective agent for treating primary pulmonary hypertension.

Amrinone as an antidote in experimental verapamil overdose.

To evaluate the effect of amrinone as a treatment for the hemodynamic effects of verapamil overdose in a canine model. This nonblind interventional study was performed in an established canine model of verapamil toxicity, without concurrent control animals. Pentobarbital-anesthetized and instrumented dogs (n = 8) were maintained and observed for 60 minutes or until death. The animals were overdosed with verapamil, 15 mg/ kg IV, over 30 minutes. Hemodynamic parameters, including cardiac index (CI), heart rate (HR), and mean arterial pressure (MAP), were monitored. Completion of the verapamil infusion represented the defined point of toxicity; at that point, all the animals received an amrinone bolus of 2 mg/kg IV over 2 minutes followed by an amrinone drip at 10 micrograms/kg/min. The hemodynamic values at the defined point of toxicity were compared with those obtained postinitiation of the amrinone infusion. Two animals died before the 60-minute observation period elapsed. Baseline CI was 5.6 L/min/m2. Following verapamil-induced toxicity, mean CI was 2.2 L/min/m2. After administration of amrinone, a significant (p < 0.05) increase in CI was observed at 30 minutes (CI = 3.6 L/min/m2), 45 minutes (CI = 4.2 L/ min/m2), and 60 minutes (CI = 4.2 L/min/m2). There was no statistically significant difference noted for MAP or HR compared with "point of toxicity" values. Amrinone appears to reverse the depressed cardiac index associated with verapamil overdose in a canine model while having no significant effect on the hypotension or bradycardia.

Amrinone reverses bupivacaine-induced regional myocardial dysfunction.

Amrinone has been shown to have therapeutic effects on bupivacaine-induced cardiovascular toxicity, but its exact effects on the heart are not well understood. This study evaluated the regional myocardial effect of amrinone on bupivacaine-induced cardiovascular toxicity in in situ beating hearts in 10 dogs using a selective coronary perfusion and sonomicrometry. In the control group, bupivacaine was administered into the left anterior descending coronary artery (LAD) for 15 min at four steps: baseline, step 1, step 2 and step 3, (calculated LAD plasma concentrations; 0, 5, 5 and 10 mu g center dot ml-1, respectively). In the amrinone group, amrinone (5 mu g center dot ml-1) was simultaneously infused at steps 2 and 3 in addition to bupivacaine infusions. Regional myocardial function of the LAD supplied area was evaluated by analysis of the left ventricular pressure-segment length loop. In the control group, systolic shortening decreased from the baseline (10.5 +/- 1.3%, mean +/- SEM) to step 3 (0.1 +/- 1.3%), and post-systolic shortening increased from the baseline (18.0 +/- 3.7%) to step 3 (52.3 +/- 5.5%) dose-dependently. In contrast, with amrinone infusion at steps 2 and 3, both variables returned to near baseline values. These results indicate that amrinone reverses bupivacaine-induced regional myocardial dysfunction.

RETRACTED ARTICLE: The dose-response relationship of amrinone in increasing the contractility of fatigued diaphragm in dogs

We studied the dose-related effects of amrinone on the contractility of a fatigued diaphragm in 16 anesthetized, mechanically ventilated dogs. The animals were divided into two groups: the control group (Group C,n=8) and the amrinone group (Group A,n=8). Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. The contractility of the diaphragm was assessed from changes in transdiaphragmatic pressure (P di). After inducing fatigue,P di at low-frequency (20 Hz) stimulation decreased significantly compared with the pre-fatigue values (P<0.05), whereas no change was observed at high-frequency (100 Hz) stimulation. In Group A, after producing fatigue,P di at 20 Hz stimulation increased significantly with a bolus injection (0.75 mg·kg(-1)) followed by continuous infusion of amrinone (2.5, 5 and then 10μg·kg(-1)min(-1)) IV (P<0.05).P di at 100 Hz stimulation increased significantly with an administration of amrinone (10μg·kg(-1)min(-1) IV (P<0.05). There was a significant positive correlation betweenP di at both stimuli and amrinone dose (P<0.01). In Group, C, the speed of recovery ofP di at 20 Hz stimulation was relatively slower. The integrated electric activity of the diaphragam (E di) in each group did not change at any frequency of stimulation throughout the experiment. We conclude that amrinone exerts a dose-dependent enhancement of the contractility of a fatigued diaphragm in dogs.

The dose?response relationship of amrinone in increasing the contractility of fatigued diaphragm in dogs

We studied the dose-related effects of amrinone on the contractility of a fatigued diaphragm in 16 anesthetized, mechanically ventilated dogs. The animals were divided into two groups: the control group (Group C, n = 8) and the amrinone group (Group A, n = 8). Diaphragmatic fatigue was induced by intermittent supramaximal bilateral elec- trophrenic stimulation at a frequency of 20 Hz applied for 30min. The contractility of the diaphragm was assessed from changes in transdiaphragmatic pressure (Pai). After inducing fatigue, Pd~ at low-frequency (20Hz) stimulation decreased significantly compared with the pre-fatigue values (P < 0.05), whereas no change was observed at high-frequency (100Hz) stimulation. In Group A, after producing fatigue, P< at 20Hz stimulation increased significantly with a bolus injection (0.75 mg.kg 1) followed by continuous infusion of amrinone (2.5, 5 and then 10vg.kg-l.min ~) IV (P < 0.05). Pdi at 100Hz stimulation increased significantly with an administration of amrinone (10~g.kg-a.min a) IV (P < 0.05). There was a sig- nificant positive correlation between Pd~ at both stimuli and amrinone dose (P < 0.01). In Group C, the speed of recovery of P~i at 20Hz stimulation was relatively slower. The inte- grated electric activity of the diaphragam (Edi) in each group did not change at any frequency of stimulation throughout the experiment. We conclude that amrinone exerts a dose- dependent enhancement of the contractility of a fatigued diaphragm in dogs.

Anesthesia for Aortic and Mitral Valve Replacement in a Patient with Carcinoid Heart Disease

Anesthesia for Aortic and Mitral Valve Replacement in a Patient with Carcinoid Heart Disease

AMRINONE COMBINED WITH DOBUTAMINE IMPROVES HEMODYNAMICS AND OXYGEN DELIVERY WITHOUT DOWN-REGULATION OF CARDIAC β-ADRENERGIC RECEPTOR DENSITY IN PORCINE ENDOTOXEMIA

Effects of amrinone (AMR), a phosphodiesterase inhibitor, alone and in combination with dobutamine (DOB), on hemodynamics and O2 delivery were studied during porcine endotoxemia. Pentobarbital-anesthetized pigs were randomly administered either Escherichia coli lipopolysaccharide (endotoxin) or equivolumetric .9% NaCl (control) as a continuous infusion for 4 h. From 2 to 4 h (T = 120-240 min) of endotoxin infusion, pigs were randomly administered one of the following treatments; AMR infusion (40 micrograms/kg/min) (AMRlow); DOB (10 micrograms/kg/min) (DOB); AMR infusion (40 micrograms/kg/min) + DOB (AMRlow+DOB); AMR bolus (.75 mg/kg) followed by AMR infusion (40 micrograms/kg/min) (AMRhigh); or AMR bolus (.75 mg/kg) followed by infusion (40 micrograms/kg/min) + DOB (AMRhigh+DOB). Myocardial samples were obtained at the end of the experiment and flash-frozen for beta-adrenergic receptor analysis. Endotoxin significantly (p < .05) decreased cardiac index, right ventricular ejection fraction, stroke volume index, maximum rate of rise of left ventricular pressure (dP/dtmax), mean arterial pressure, and O2 delivery, and increased pulmonary vascular resistance and mean pulmonary arterial pressure (p < .05). AMRlow+DOB significantly (p < .05) increased cardiac index, dP/dtmax, right ventricular ejection fraction, stroke volume index, O2 delivery and consumption, and decreased mean pulmonary arterial pressure, pulmonary vascular resistance, mean arterial pressure, and systemic vascular resistance. beta-Adrenergic receptor density (Bmax) and binding equilibrium dissociation constant (KD) for [3H]dihydroalprenolol were not affected by endotoxin or any treatment (p < .05). Endotoxin-induced hemodynamic deterioration and decreased O2 delivery was attenuated by AMRlow+DOB. Potential applications of this combination may exist in treatment of septic patients with inadequate myocardial performance and reduction in O2 delivery complicated by pulmonary hypertension.

A Randomized Comparison of Intravenous Amrinone Versus Dobutamine in Older Patients with Decompensated Congestive Heart Failure

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. Prospective, randomized, double-blind clinical trial. Coronary care unit of a university teaching hospital. 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%). 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. 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. 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. 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.

Reversal of ‘Refractory Septic Shock’ by Infusion of Amrinone and Angiotensin II in an Anthracycline-Treated Patient

A 53-year-old granulocytopenic woman with malignant lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, including doxorubicin (Adriamycin) and autologues bone marrow transplantation, presented in the clinical state of "refractory septic shock" caused by Escherichia coli. Despite inotropic treatment with dopamine, dobutamine, and norepinephrine infusion, the patient's condition did not improve, but during treatment with amrinone and angiotensin II infusion, the septic shock was reversed. The patient was monitored with a pulmonary artery catheter and underwent repeated echocardiographic examinations. Antibiotic treatment with thienamycin and floxacillin was given. The initial reduction in cardiac performance in this patient may be explained by a state of true down-regulation of the myocardial beta-receptors. Apparently these beta-receptors were bypassed via the enzymatic action of amrinone upon cyclic monoadenosine phosphate. This is, to our knowledge, the first doxorubicin-treated patient with septic shock refractory to conventional vasopressor therapy whose condition reversed by inotropic treatment with amrinone and angiotensin II. This treatment may prove to be an alternative choice for patients developing "refractory septic shock" unresponsive to treatment with norepinephrine, dobutamine, and dopamine.