OBJECTIVETo investigate the protective effect of amrinone against experimental lung ischemia /reperfusion (I/R) injury.

METHODSTwenty-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.

RESULTSAfter 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.

CONCLUSIONSAmrinone has protections against lung I/R injury, possibly through its anti-oxidation effects and an inhibition of inflammation factors releasing.

Amrinone ; therapeutic use ; Animals ; Interleukin-1beta ; blood ; Interleukin-8 ; blood ; Lung ; blood supply ; drug effects ; Male ; Malondialdehyde ; analysis ; Phosphodiesterase Inhibitors ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; metabolism ; pathology ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; blood

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.
Amrinone/administration and dosage ; Animals ; Calcium Chloride/administration and dosage ; Cardiotonic Agents/*administration and dosage ; Comparative Study ; Dobutamine/administration and dosage ; Dogs ; Dose-Response Relationship, Drug ; Epinephrine/administration and dosage ; Female ; Male ; Myocardial Contraction/*drug effects ; Myocardial Stunning/*drug therapy/etiology/*physiopathology ; Oxidation-Reduction/drug effects ; Oxygen Consumption/*drug effects ; Reperfusion Injury/complications/*drug therapy/*physiopathology ; Treatment Outcome

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.
Amrinone* ; Animals ; Coronary Vessels ; Dobutamine* ; Dogs* ; Ischemia ; Lactic Acid ; Myocardial Stunning* ; Myocardium ; Oxygen Consumption ; Oxygen* ; Reperfusion ; Reperfusion Injury ; Vasodilation ; Ventricular Pressure

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.
Amrinone* ; Animals ; Cyclic Nucleotide Phosphodiesterases, Type 3* ; Heart ; Hydrogen Peroxide ; Hydroxyl Radical ; Ischemia ; Myocardium ; Neutrophils ; Peroxidase ; Rats ; Reactive Oxygen Species ; Reperfusion ; Superoxides

OBJECTIVETo 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.

METHODSThirty-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.

RESULTSAll 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).

CONCLUSIONThe dexamethasone, aminoguanidin, amrinone can improve oxygen utilization in endotoxic shock rabbits, especially for dexamethasone and aminoguanidin.

Amrinone ; therapeutic use ; Animals ; Anti-Inflammatory Agents ; therapeutic use ; Dexamethasone ; therapeutic use ; Enzyme Inhibitors ; therapeutic use ; Female ; Guanidines ; therapeutic use ; Male ; Nitric Oxide Synthase ; antagonists & inhibitors ; Oxygen Consumption ; drug effects ; Phosphodiesterase Inhibitors ; therapeutic use ; Rabbits ; Shock, Septic ; drug therapy ; Treatment Outcome ; Vasodilator Agents ; therapeutic use

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.
Amrinone ; Anesthesia ; Arterial Pressure ; Cardiopulmonary Bypass* ; Coronary Artery Bypass* ; Coronary Vessels* ; Fentanyl ; Hemodynamics ; Humans ; Incidence ; Intensive Care Units ; Isosorbide Dinitrate ; Isosorbide* ; Lung Injury ; Oxygen* ; Propofol ; Vecuronium Bromide ; Ventilation

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.
Amrinone* ; Animals ; Arteries ; Dobutamine ; Dogs* ; Ischemia ; Lactic Acid ; Myocardial Stunning* ; Myocardium ; Oxygen Consumption ; Oxygen* ; Reperfusion ; Reperfusion Injury ; Transducers ; Ultrasonics ; Vasodilation

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.
Amrinone* ; Animals ; Blood Pressure ; Cardiac Output ; Catecholamines ; Coronary Vessels ; Depression ; Dobutamine ; Dogs* ; Dopamine ; Heart Failure* ; Heart* ; Hemodynamics* ; Humans ; Critical Care ; Ligation ; Myocardial Infarction ; Nitroglycerin ; Nitroprusside ; Oxygen ; Perioperative Period ; Vascular Resistance ; Vasodilator Agents ; Ventricular Function

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.
Amrinone* ; Animals ; Blood Pressure ; Cardiac Output ; Catecholamines ; Coronary Vessels ; Depression ; Dobutamine ; Dogs* ; Dopamine ; Heart Failure* ; Heart* ; Hemodynamics* ; Humans ; Critical Care ; Ligation ; Myocardial Infarction ; Nitroglycerin ; Nitroprusside ; Oxygen ; Perioperative Period ; Vascular Resistance ; Vasodilator Agents ; Ventricular Function

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.
Amrinone* ; Anesthesia ; Atropine ; Cardiopulmonary Bypass ; Clonidine* ; Coronary Artery Bypass* ; Coronary Vessels* ; Dopamine* ; Hemodynamics ; Humans ; Isosorbide Dinitrate ; Operating Rooms ; Perfusion ; Phenylephrine ; Premedication ; Reference Values ; Weaning