Protection of amrinone against lung injury induced by ischemia/reperfusion in rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of amrinone against experimental lung ischemia /reperfusion (I/R) injury.</p><p><b>METHODS</b>Twenty-four Sprague-Dawley rats were randomly divided into 3 groups (n=8 each): sham- operated group, I/R group, and amrinone-treated I/R group (AMR group). The left lung of rats was subjected to ischemia for 90 minutes, followed by reperfusion for 2 hrs, to induce an I/R lung injury model. The rats of the AMR group received amrinone (10 mg/kg) intravenously 30 minutes before ischemia and 5 minutes before reperfusion. After 2 hrs of reperfusion, carotid artery blood was collected for blood-gas analysis and detection of serum levels of IL-1beta, IL-8 and TNF-alpha. The left lung was removed for detection of the lung wet/dry ratio, the erythrocuprein (SOD) activity and the malonaldehyde (MDA) content as well as the pathological changes.</p><p><b>RESULTS</b>After 2 hrs of reperfusion, there were no significant differences in artery partial pressure of oxygen (PO2) and partial pressure of carbon dioxide (PCO2) among the three groups. The lung wet/dry ratio (5.3 +/- 0.5 vs 4.8 +/- 0.1) and the MDA content (0.66 +/- 0.16 nmol/mg prot vs 0.47 +/- 0.06 nmol/mg prot) in the I/R group were significantly higher than those of the sham-operated group (P <0.05). The administration of amrinone markedly reduced the lung wet/dry ratio (4.8 +/- 0.2) and the MDA content (0.51 +/- 0.09 nmol/mg prot) and increased the SOD activity (54.7 +/- 6.8 vs 39.3 +/- 3.0 U/mg prot) when comparing the I/R group (P < 0.05). The serum levels of IL-1beta, IL-8 and TNF-alpha in the I/R group were 22.08 +/- 3.85, 21.92 +/- 5.56 and 30.50 +/- 3.77 pg/mL respectively, which were significantly higher than those of the sham-operated group. The AMR group showed lower serum levels of IL-1beta, IL-8 and TNF-alpha (16.66 +/- 3.02,14.73 +/- 2.75 and 22.48 +/- 3.82 pg/mL, respectively) compared with the I/R group (P < 0.01). The pathologic examination displayed that the lung tissue structure was normal and there was no hyperemia in the sham-operated and the AMR groups. The lung tissue structure of the I/R group was nearly normal but there were hyperemia and more inflammatory cells than the sham-operated and the AMR groups.</p><p><b>CONCLUSIONS</b>Amrinone has protections against lung I/R injury, possibly through its anti-oxidation effects and an inhibition of inflammation factors releasing.</p>

Effects of Amrinone and Dobutamine on Regional Myocardial Function and Oxygen Balance in Normal and Stunned Myocardium in Dogs / 대한구급학회지

BACKGROUND: We examined the effects of amrinone and dobutamine on regional mechanical function, coronary blood flow (CBF), and myocardial oxygen consumption (MVO2) in normal and stunned myocardium in an open-chest canine model. METHODS: Dogs were instrumented to measure aortic and left ventricular pressures, pulmonary and left anterior descending (LAD) coronary blood flows, and subendocardial segment length in the region supplied by LAD. Incremental doses of either amrinone (2~10microgram/ml of LAD flow, n=13) or dobutamine (0.05~0.375microgram/ml of LAD flow, n=14) were directly infused into a coronary artery before (normal) and after a 15 min of LAD occlusion and subsequent 30 min-reperfusion (stunned). Percent segment shortening (%SS) and percent post-systolic shortening (%PSS) were evaluated. Myocardial extraction of oxygen (EO2) and lactate (Elac) was calculated. RESULTS: Amrinone or dobutamine in the normal myocardium caused dose-dependent increases in %SS that were comparable (range, 20~40%) but had no effect on %PSS. MVO2 increased in parallel with %SS for both amrinone and dobutamine. With amrinone, CBF increased more than MVO2, resulting in a modest decrease in EO2, whereas with dobutamine, CBF increased in proportion to MVO2, resulting in no change in EO2. After the ischemia and reperfusion, %SS and Elac were reduced, but similar %SS and CBF responses to both agents were observed, except that both agents caused progressive reductions of %PSS. CONCLUSIONS: These results indicate that both amrinone and dobutamine exert positive inotropic effects in normal and stunned canine myocardium. It is also indicated that amrinone causes direct coronary vasodilation, which is not affected by ischemia and reperfusion, while dobutamine has no direct effect on coronary vascular tone in either normal or stunned myocardium.

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.

Cardiac and vascular effects of diltiazem, dobutamine and amrinone, drugs used after myocardial revascularization

Hemodynamic care during postoperative management of myocardial revascularization should include vasorelaxing drugs to insure adequate graft and coronary flow, and stimulation of stroke volume to maintain vascular perfusion pressure. We tested the cardiac (inotropic and lusitropic) and vascular (relaxant) effects of diltiazem (0.1 nM to 0.1 mM), dobutamine (10 æM to 10 mM) and amrinone (10 æM to 1 mM) on isolated rat atria and thoracic aorta, and also on isolated human saphenous vein (HSV) and human mammary artery (HMA). Dobutamine produced a maximal positive inotropic effect (+dF/dt max = 29 ñ 7 percent) at its ED50 for aortic relaxation (88 ñ 7 æM). Conversely, at their ED50 for aortic relaxation diltiazem depressed myocardial contractility and amrinone did not exhibit myocardial effects. In HSV and HMA contracted with 80 mM potassium, diltiazem and dobutamine (but not amrinone) had a vasorelaxant activity similar to that in rat aorta. Norepinephrine-contracted human vessels were significantly more sensitive than potassium-contracted vessels to the relaxant effect of amrinone (ED50 HMA = 15 ñ 5 æM, ED50 HSV = 72 ñ 31 æM, P < 0.05). We conclude that at concentrations still devoid of myocardial effects dobutamine and amrinone are effective dilators in graft segment vessels and rat aorta contracted by membrane depolarization. If the difference between aortic and myocardial tissue still holds in human tissues, at the appropriate concentrations these drugs should be expected to improve cardiac performance while still contributing to the maintenance of graft patency.

Effect of Amrinone, a Selective Inhibitor of Phosphodiesterase III, on PMNs-induced Cardiac Dysfunction in Ischemia/reperfusion

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. Amrinone, a specific inhibitor of phosphodiesterase 3, has an antioxidant activity against PMNs. Therefore, we hypothesized that amrinone could attenuate PMNs-induced cardiac dysfunction by suppression of reactive oxygen species (ROS) produced fby PMNs. In the present study, we examined the effects of amrinone on isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Amrinone at 25microM, given to hearts during the first 5 min of reperfusion, significantly improved coronary flow, left ventricular developed pressure (P< 0.001), and the maximal rate of development of left ventricular developed pressure (P< 0.001), compared with ischemic/reperfused hearts perfused with PMNs in the absence of amrinone. In addition, amrinone significantly reduced myeloperoxidase activity by 50.8%, indicating decreased PMNs infiltration (p< 0.001). Superoxide radical and hydrogen peroxide production were also significantly reduced in fMLP- and PMA-stimulated PMNs pretreated with amrinone. Hydroxyl radical was scavenged by amrinone. fMLP-induced elevation of [Ca2+]i was also inhibited by amrinone. These results provide evidence that amrinone can significantly attenuate PMN-induced cardiac contractile dysfunction in the ischemic/ reperfused rat heart via attenuation of PMNs infiltration into the myocardium and suppression of ROS release by PMNs.

Effect of dexamethasone, aminoguanidin, amrinone on oxygen utilization in endotoxin shock rabbits / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of three kinds of drug with different mechanism, dexamethasone (Dex), aminoguanidin (AG) and amrinone (Amr) on oxygen utilization in endotoxic shock rabbits.</p><p><b>METHODS</b>Thirty-five rabbits were randomly allocated into five groups: operation, lipopolysaccharide (LPS), Dex, Amr and AG. The endotoxin shock was induced by intravenously injecting LPS (400 micro g/kg). The arterial blood gas, mixed venous blood gas and cardiac output were recorded at 30 min after the operation (T(0)), shock status (T), 1 - 6 h after the treatment (T(1)-T(6)). The oxygen delivery (DO(2)), oxygen consumption (VO(2)) and extraction ratio of oxygen (ERO(2)) were calculated.</p><p><b>RESULTS</b>All the parameters in five groups showed no significant differences (P > 0.05) at T(0). Six hours after treatment, rabbits in Dex group presented with significantly improved DO(2) (12.4 +/- 3.1) ml/(kg.min), P < 0.01 and VO(2) (5.1 +/- 1.6) ml/(kg.min), P < 0.05 compared with DO(2) (8.1 +/- 2.4) ml/(kg.min) and VO(2) (2.7 +/- 1.0) ml/(kg.min) in LPS group. Rabbits in AG group showed significantly increased DO(2) (17.0 +/- 2.8) ml/(kg.min) (P < 0.01), (17.2 +/- 2.5) ml/(kg.min) (P < 0.05), compared with (12.2 +/- 2.6), (14.1 +/- 3.8) ml/(kg.min) in LPS group at T(1) and T(2), respectively, but there was no significant difference (11.2 +/- 1.7) ml/(kg.min) (P > 0.05) at T(6). The VO(2) increased significantly, (5.0 +/- 1.0) ml/(kg.min) (P < 0.01) compared with LPS group at T(6). The VO(2) of Amr group was significantly higher than LPS group at T(3) and T(4). At T(6), the DO(2) and VO(2) were (9.5 +/- 1.3) and (4.1 +/- 1.5) ml/(kg.min), respectively, but there was no significant difference compared with LPS group. There was no significant difference in ERO(2) among groups (P > 0.05).</p><p><b>CONCLUSION</b>The dexamethasone, aminoguanidin, amrinone can improve oxygen utilization in endotoxic shock rabbits, especially for dexamethasone and aminoguanidin.</p>

A Ratio of Arterial Oxygen Tension to Inspired Oxygen Fraction (PaO2/FiO2 ratio) after Cardiopulmonary Bypass in Coronary Artery Bypass Graft Surgery: Amrinone-Dopamine versus Isosorbide Dinitrate-Dopamine / 대한마취과학회지

BACKGROUND: Cardiopulmonary bypass (CPB) may produce lung injury with decreased PaO2/FiO2 ratio in patients undergoing CABG surgery. We examined PaO2/FiO2 ratio and incidence of PaO2/FiO2 < 300 or 150 to determine the differences in oxygenation with the use of amrinone-dopamine (DP) or isosorbide dinitrate (IDN)-DP in patients undergoing CABG. METHODS: Twenty patients undergoing elective CABG were divided into two groups according to drug used on separation from CPB: IDN-DP (Group 1, n = 10) or amrinone-DP (Group 2, n = 10). Anesthesia was induced and maintained with propofol, fentanyl and vecuronium. IDN infusion (1.0microgram/kg/min) was started preoperatively in both groups. Mild hypothermic CPB was applied with a roller pump and nonpulsatile flow maintained a mean arterial pressure of 60-80 mmHg. In Group 2, amrinone was administered (0.75 mg/kg + 10microgram/kg/min) instead of IDN at the time of CPB separation. DP infusion (3microgram/kg/min) was started at a rectal temperature more than 35.5oC and adjusted to maintain acceptable hemodynamics. IDN-DP or amrinone-DP infusion, monitoring and sedation with propofol were continued in the intensive care unit (ICU). PaO2/FiO2 ratio under controlled ventilation with air/O2 mixture (FiO2 0.6) was checked immediately before CPB (pre-CPB), 30 mins (post-CPB30), 60 mins after CPB (post-CPB60) and 30 mins after admission to ICU (ICU30). RESULTS: There was no significant difference between the groups in the terms of the duration of arotic cross clamp, PaO2/FiO2 at pre-CPB, PaO2/FiO2 at post-CPB60, PaO2/FiO2 at ICU30 or in the incidence of PaO2/FiO2 < 150, PaO2/FiO2 < 300 at ICU30. But there was a significant difference in PaO2/FiO2 post CPB30 (263.3 +/- 105.5 in Group 1 vs. 381.7 +/- 69.5 in Group 2, P<0.05). CONCLUSIONS: Amrinone-DP provides more favorable oxygenation immediately after CPB in CABG surgery than IDN-DP.

Effects of Amrinone on Regional Myocardial Function and Oxygen Balance in Stunned Myocardium in Dogs / 대한마취과학회지

BACKGROUND: Brief myocardial ischaemia has been demonstrated to result in mechanical and coronary endothelial dysfunction. We examined whether the mechanical and vascular responses to amrinone are altered in the postischaemic, reperfused myocardium. The effects of amrinone were compared with those of dobutamine. METHODS: In an open-chest canine model, coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and regional mechanical function in response to either amrinone (2, 5, 7.5, and 10 ng/mL of CBF) or dobutamine (0.05, 0.125, 0.25, 0.375, and 10ng/mL of CBF) directly infused into the left anterior descending (LAD) artery were determined before (normal) and 30 min after 15-min- period of LAD occlusion (stunned). Percent segment shortening (%SS), peak segment lengthening rate (dL/dt(max)), and percent post-systolic shortening (%PSS) in the LAD territory was determined using ultrasonic crystals and CBF using Doppler transducer. Myocardial extractions of oxygen (EO2) and lactate (Elac) were calculated. RESULTS: Both amrinone and dobutamine in the normal myocardium caused a dose-dependent increase in mechanical functions (%SS and dL/dt(max)) and MVO2 that were comparable (range, 20 40%), but they had no effects on %PSS. Amrinone caused an increase of CBF in excess of MVO2, resulting in a modest decrease in EO2, whereas dobutamine increased CBF in proportion to MVO2, resulting in no changes in EO2. The ischemia and reperfusion insult reduced %SS, dL/dt(max), and Elac, while it did not affect mechanical (%SS and dL/dt(max)) and CBF responses to either agent, except for progressive reductions of %PSS. CONCLUSIONS: These results indicate that amrinone, similar to dobutamine, exert positive inotropic and lusitropic effects in normal and stunned canine myocardium. It is also indicated that amrinone causes direct coronary vasodilation, which is not affected by an ischemia and reperfusion insult.

Anesthetic Management of Ovarian Bleeding with Eisenmenger's Syndrome: A case report / 대한마취과학회지

Eisenmenger's syndrome is defined as a high pulmonary vascular resistance associated with pulmonary hypertension or high pulmonary pressure close to systemic values with a reverse or bidirectional shunt at aortopulmonary, interventricular or interatrial levels. We report the case of a 42-year-old woman with an emergency operation for ovarian bleeding with Eisenmenger's syndrome secondary to large VSD. She had abdominal pain and vaginal spotting which developed one month earlier. In a preoperative abdominal ultrasonography, there was a fluid collection on the Cul-de-sac. There was no significant cardiorespiratory symptom except peripheral cyanosis. Anesthesia was performed with fentanyl, midazolam and vecuronium in standard monitorings including pulmonary artery pressure monitoring. Bolus and continuous infusions of amrinone were given to decrease right to left shunt. After the administration of amrinone, PaO2, PaO2/FiO2, P(A-a)O2 and P(a/A)O2 were improved and pulmonary arterial pressure was preferentially decreased compared with systemic arterial pressure. There was no significant problem throughout the operation, a right ovarian wedge resection. She was transferred to the intensive care unit in an intubated state postoperatively and discharged one week later without any complications.

Comparison of Amrinone and Dopamine-Nitroglycerin on Hemodynamic Parameters in Dogs with Postinfarct Heart Failure / 대한마취과학회지

BACKGROUND: Left ventricular failure (LVF) after an acute myocardial infarction occurs during the perioperative period, and since this condition can lead to severe complications, intensive care is required for the patient. LVF is characterized hemodynamically by a raised left heart filling pressure and volume and global depression of the hearts pumping performance. Several effective drugs for patients with heart failure are catecholamines such as dopamine and dobutamine, vasodilators such as nitroglycerin and nitroprusside, and noncatecholamine inotropes such as amrinone, which are either infused alone or in combination. However, as of now, there has been no study as to clarifying either the exact dosage, drug combination, or how they affect the heart. METHODS: By inducing a state of experimental acute left ventricular failure in 20 dogs through ligation of the left anterior descending coronary artery, this study compared the hemodynamic parameters of two treatment groups-one group using amrinone alone (bolus 1 mg/kg, continuous infusion 15micro gram/kg/min), and another group using a combination of dopamine (10micro gram/kg/min) and nitroglycerin (2micro gram/kg/min). RESULTS: Cardiac output of dogs with postinfarct heart failure increased in both treatment groups. But, there was a significant decrease in systemic vascular resistance, pulmonary vascular resistance and left ventricular end diastolic pressure in the group treated with amrinone than dopamine-nitroglycerin. Amrinone also revealed a favorable effect on oxygen utility. CONCLUSIONS: These results showed that amrinone might be more effective than the combination of dopamine and nitroglycerin for acute left ventricular failure in terms of myocardial function, hemodynamic stability and oxygen utility.

Comparison of Amrinone and Dopamine-Nitroglycerin on Hemodynamic Parameters in Dogs with Postinfarct Heart Failure / 대한마취과학회지

BACKGROUND: Left ventricular failure (LVF) after an acute myocardial infarction occurs during the perioperative period, and since this condition can lead to severe complications, intensive care is required for the patient. LVF is characterized hemodynamically by a raised left heart filling pressure and volume and global depression of the hearts pumping performance. Several effective drugs for patients with heart failure are catecholamines such as dopamine and dobutamine, vasodilators such as nitroglycerin and nitroprusside, and noncatecholamine inotropes such as amrinone, which are either infused alone or in combination. However, as of now, there has been no study as to clarifying either the exact dosage, drug combination, or how they affect the heart. METHODS: By inducing a state of experimental acute left ventricular failure in 20 dogs through ligation of the left anterior descending coronary artery, this study compared the hemodynamic parameters of two treatment groups-one group using amrinone alone (bolus 1 mg/kg, continuous infusion 15micro gram/kg/min), and another group using a combination of dopamine (10micro gram/kg/min) and nitroglycerin (2micro gram/kg/min). RESULTS: Cardiac output of dogs with postinfarct heart failure increased in both treatment groups. But, there was a significant decrease in systemic vascular resistance, pulmonary vascular resistance and left ventricular end diastolic pressure in the group treated with amrinone than dopamine-nitroglycerin. Amrinone also revealed a favorable effect on oxygen utility. CONCLUSIONS: These results showed that amrinone might be more effective than the combination of dopamine and nitroglycerin for acute left ventricular failure in terms of myocardial function, hemodynamic stability and oxygen utility.

Effects of Clonidine on the Requirements of Dopamine Used as a Concomitant Drug of Amrinone in Coronary Artery Bypass Surgery (CABG) / 대한마취과학회지

BACKGROUND: Clonidine premedication has many beneficial effects in patients undergoing CABG surgery. Amrinone, having the ability to increase cardiac performance without increasing myocardial O2 consumption, is a valuable drug in postoperative management after cardiopulmonary bypass (CPB). The use of amrinone with a catecholamine is also important clinically because the cathecholamines support perfusion pressure and the combined use exerts synergistic or additive effects. We performed this study to examine whether clonidine premedication could change the amount of dopamine used concomitantly with amrinone for management after CPB. METHODS: Nineteen patients for elective CABG were allocated to two groups according to their premedication; a placebo (Group 1, n = 13) or clonidine 4 microgram/kg p.o. (Group 2, n = 6). All patients arrived in the operating room with infusion of isosorbide dinitrate (ID). Anesthesia was performed with standard techniques. Before initiation of CPB, significant lowering of BP or HR was treated with phenylephrine or atropine respectively. Amrinone was given bolus (0.75 mg/kg) and infusion (10 microgram/ kg/min) was begun instead of ID at the release of aortic cross-clamp. Dopamine infusion (3 microgram/kg/min) was started at 35degree C (rectal) and its rate was adjusted for maintaining acceptable hemodynamics. We compared the amount of infused dopamine within 90 mins after CPB between the two groups. We also compared systolic BP, HR and CVP before induction, 10 mins after induction and 60 mins after CPB. RESULTS: Systolic BP and HR before induction and HR 10 mins after induction were significantly lower in Group 2 (P < 0.05), but they were all within normal range. The proportion of patients who needed phenylephrine or atropine before CPB was not significantly different in the two groups. The amount of infused dopamine was significantly larger in Group 2 (P < 0.05). Hemodynamics were acceptable after CPB although HR 60 min after CPB was significantly lower within the normal range in Group 2 (P < 0.05). Weaning time from CPB was not significantly different in the two groups. No significant adverse effect was observed throughout this study. CONCLUSIONS: Clonidine, used as premedication, increases the need of catecholamine which is concomitantly administered with amrinone for weaning from CPB. But this method provides clinically effective result without jeopardizing hemodynamics in CABG.

Hemodynamic Responses and Changes in Oxygen Extraction When Using Amrinone, Dobutamine and Isoproterenol in Cardiac Tamponade-Induced Dogs / 대한마취과학회지

BACKGROUND: Cardiac tamponade is most commonly treated by needle aspiration or surgical drainage. During this process, it may be necessary to temporarily improve cardiac output and to maintain peripheral perfusion by using vasoactive drugs and volume expanders. The purpose of this study is to examine the hemodynamic effect along with oxygen availability on cardiac tamponade induced dogs caused by the use of dobutamine, isoproterenol and amrinone following pentastarch infusion. METHODS: Twenty-four dogs were divided into four groups including a control group (group I), which received only pentastarch 10 ml/kg after artifical tamponade was induced. Following the administration of pentastarch, group II (n = 6) received dobutamine by dripping 10 microgram/kg/min, and then by 20 microgram/ kg/min, group III (n = 6) received isoproterenal (0.5 microgram/kg/min, 1.0 microgram/kg/min) and group IV (n = 6) received amrinone (50 microgram/kg/min, 100 microgram/kg/min). The hemodynamic parameters were measured in seven intervals: baseline, thoracotomy, tamponade, tamponade plus pentastarch, pentastarch plus dripping (1st dose), pentastarch plus drug (2nd injection = two times the 1st dose), and pericardiostomy. Arterial and mixed venous blood gas analyses were carried out in three intervals: after thoracotomy, tamponade, pentastarch plus drug (infusion). Subsequently, oxygen extraction ratios were calculated from the oxygen delivery and oxygen consumption. RESULTS: The heart rate increased significantly during the infusion of isoproterenol (P = 0.032) 1.0 microgram/kg/min in group III and also during the dobutamine infusion when the pericardiostomy (P = 0.028) was performed in group II. Compared to the control group, cardiac output increased significantly in group II from the infusion of the 1st dose and also in group III with the 2nd dose infusion but there were no significant changes in group IV. Although the average intrapericardial pressure was 0.93 mmHg in each group and was increased to 8.23 mmHg during the induced tamponade, no significant changes occurred in the groups with drug infusion. The oxygen extraction ratio fell significantly in the groupII, III and IV during the drug infusion. CONCLUSIONS: As results of this study, it was concluded that the most effective hemodynamic improvements during the induced cardiac tamponade occured in group II with pentastarch-dobutamine while the least effective combination occurred in group IV with pentastarch-amrinone.

Effects of Amrinone on Systemic and Pulmonary Arterial Pressure in Infants with Intracardiac Left to Right Shunt / 대한마취과학회지

BACKGROUND: Amrinone is a nonglycosidic noncatecholamine with both vasodilator and positive inotropic effects that has not been evaluated widely in pediatric patients with intracardiac left to right shunts. The present study was performed to evaluate the hemodynamic effects of amrinone in infants and children with intracardiac left to right shunts. METHODS: Twenty patients (aged 2 months to 24 months) who underwent open heart surgery to correct one or more intracardiac left to right shunts were evaluated. Before cardiopulmonary bypass, a 22 gauge angiocatheter was placed at the main pulmonary artery by surgeons to measure pulmonary arterial pressure. Patients with a mean pulmonary arterial pressure or = 25 mmHg were assigned to Group B (n = 10). Mean systemic arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP) and heart rate (HR) were measured before loading of amrinone (3 mg/kg), 5 minutes, and 15 minutes after continuous infusion of amrinone (10 microgram/kg). The mean pulmonary arterial pressure to mean systemic arterial pressure ratio (MPAP/MAP) and rates of changes of mean arterial pressure (delta MAP) and mean pulmonary arterial pressure (delta MPAP) were calculated. RESULTS: Amrinone reduced MAP, MPAP, CVP and increased HR. MPAP/MAP increased in Group A but decreased in Group B (P < 0.05). In Group A, delta MAP was significantly greater than that of Group B (P < 0.005). In Group B, delta MPAP was significantly greater than that of Group A (P < 0.005). CONCLUSION: In infants with intracardiac left to right shunts, amrinone reduces MAP, MPAP, CVP and increases HR. Amrinone appears to have a potent vasodilating effect on the pulmonary artery in infants with pulmonary hypertension. However, more hemodynamic measurements such as cardiac output, vascular resistance and doppler echocardiographic study are necessary to evaluate the hemodynamic effects of amrinone precisely.

Efecto agudo de dobutamina y amrinona sobre la hemodinamia y perfusión esplácnica de pacientes en shock séptico / Acute effect of dobutamine and amrinone on hemodynamics and splanchnic perfusion in septic shock patients

Background: Vasoactive drugs used in the reanimation of septic patients, can modify splanchnic perfusion. Aim: To compare the effects of dobutamine and amrinone on gastric intramucosal pH (pHi), lactate levels and hemodynamics in surgical patients with compensated septic shock. Patients and methods: Fourteen postoperative patients with abdominal sepsis and compensated septic shock (pHi <7.32 or lactate >2.5 mmol/l) were studied in a prospective, randomized, unblinded study. Patients were randomized to receive (Group 1, n=7) dobutamine at 5 µg/Kg/min or (Group 2, n=7) amrinone at 5 µg/Kg/min. Hemodynamic data, arterial lactate and pHi were measured before and 30, 60 and 120 minutes after starting drug infusion. Results: Both drugs were associated with a decrease in lactate levels. Dobutamine infusion, but not amrinone, increased gastric pHi, as well as cardiac index and oxygen delivery. Conclusions: An improvement in gastric pHi associated with an increase in oxygen delivery, was observed with dobutamine. Amrinone showed no effect at the fixed, low dose used in the study

Attenuating Effect of cAMP on Hypoxic Pulmonary Vasoconstriction in the Isolated Perfused Rat Lungs / 대한마취과학회지

BACKGROUND: Pulmonary vessels constrict when they are exposed to hypoxia, unlike other vessels. It is hypothesized that the decreased concentration of cAMP in the hypoxic condition causes this reaction, HPV (hypoxic pulmonary vasoconstriction). When cAMP concentration is increased by either activating adenylate cyclase, using adenosine, or inhibiting the cAMP hydrolysing enzyme, phosphodiesterase type 3, using amrinone, then HPV can be reversed. The aims of this study were to develop HPV in an isolated perfused rat lung preparation, and to investigate the vasodilating effects of adenosine and amrinone on HPV. METHODS: Isolated lungs from male rats (270 330 g) were ventilated with a normoxic gas mixture (21%O2-5%CO2-74%N2) or a hypoxic gas mixture (3%O2-5%CO2-92%N2) alternately, and perfused with calcium-containing perfusate solution. Adenosine (6 x 100-2 microgram, n = 6) and amrinone (5 x 101-3 microgram, n = 6) were mixed to perfusate solution, and the initial hypoxic pressor response { Pin = Pmax (maximum pulmonary artery pressure) - Pin (initial pulmonary artery pressure)} and hypoxic pressor responses after drug administration { Pdrug = Pmax (maximum pulmonary artery pressure) - Pbase (baseline pulmonary artery pressure)} were measured. Meclofenamate was used to block prostaglandin-mediated vasorelaxation. RESULTS: Adenosine did not decrease Pdrug compared to Pin. But amrinone inhibited HPV effectively a with a linear dose-response relationship (r = 0.842, P< 0.05). y = 26.72 x log (x) 35.79y: % relaxation = 100 [ Pdrug/ Pin] 100 , x: amount of drug, microgram, CONCLUSIONS: Amrinone attenuated HPV, and it can be concluded that increased levels of cAMP helpful to relax pulmonary vessels in hypoxic condition.

Effects of Amrinone on the Vascular Tension of the Isolated Rabbit Pulmonary Artery / 대한마취과학회지

BACKGROUND: Amrinone is a noncatecholamine, nonglycoside compound, which is known to possess both cardiac inotropic and vasodilatory actions. This drugs has been increasingly used in clinical practice for the management of low cardiac output syndrome during anesthesia, particularly for patients associated with right heart failure and pulmonary hypertension. The aim of this study was to explore the direct vasoactive effect of amrinone and its action mechanisms in the isolated rabbit pulmonary artery. METHODS: The rabbits' pulmonary arteries were dissected free and cut into rings (3 4 mm) and mounted for isometric tension in a tissue chamber. The effects of amrinone (5 10 6 5 10 4 M) on the vascular tension were assessed in the by KCl (40 mM)- or norepinephrine (NE, 10 6 M)- precontracted pulmonary arterial rings with or without endothelium. Also effects of K channel blockers (tetraethyl ammonium 20 mM, glybenclamide 2.5 10 5 M, 4-aminopyridine (4-AP) 5 10 4 M), protein kinase A & G inhibitor (H8), L-NAME, methylene blue and indomethacin on the amrinone- induced vascular responses were investigated. Also studied was effects of amrinone on the Ca2 influx through voltage operated channel (VOC) and receptor operated channel (ROC) of the vascular cells. RESULTS: Amrinone produced vasorelaxation of KCl- or NE-precontracted pulmonary artery in a dose-dependent fashion. The amrinone-induced vasorelaxation was not affected by the denudation of the endothelium. Pretreatment with L-NAME and methylene blue did not affect the vasodilatory effect of amrinone, suggesting that nitric oxide is not involved. Following pretreatment with indomethacin (a cyclooxygenase inhibitor) or K channel blockers, the amrinone-induced vasorelaxation was not altered. After exposure to Ca2 free solution, amrinone attenuated the KCl- or NE-induced contraction even in the presence of Ca2 , implying that VOC and ROC are blocked by amrinone. On the other hand, protein kinase A blocker (H8) completely abolished the amrinone-induced relaxation in the KCl-precontracted pulmonary artery. CONCLUSIONS: These findings suggest that the amrinone-induced vasorelaxations result from inhibition of VOC and ROC as well as from the activation of protein kinase A in the isolated rabbit pulmonary artery.

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

Modulatory effects of diltiazem on inotropic responses to amrinone on rabbit isolated atria.

The effect of pretreatment with graded concentration of diltiazem on the inotropic responses to amrinone were studied on isolated atria of rabbit. The responses to amrinone were modified by diltiazem in a biphasic manner; initial potentiation followed by inhibition. The potentiation is proposed to be due to synergistic rise in cytosolic calcium ion concentration by diltiazem and amrinone. The inhibition by diltiazem in higher concentration may be due to blockade of calcium ion influx and depletion of intracellular calcium ion from storage sites.