Comparison of the initial hospitalization costs between the patients treated with dobutamine and the patients treated with amrinone for acute decompensated heart failure in a Japanese institute.

OBJECTIVES: Phosphodiesterase (PDE) III inhibitor therapy is effective for treatment of acute decompensated heart failure (ADHF). Nevertheless, this drug is expensive than conventional inotropic agent dobutamine. We compared total medication costs of the patients treated with PDE III inhibitor amrinone therapy to that of the patients treated with conventional dobutamine therapy during initial hospitalization. METHODS: We analyzed 160 consecutive patients with ADHF admitted to our hospital. Shock, dehydration, severe infection, multiple organ failure, and mild heart failure (New York Heart Association class IIs) were not eligible for the study. Ninety-seven patients were divided into two groups: 1) DOB group treated with dobutamine therapy; and 2) AMR group treated with amrinone therapy. Total medication costs and cost for hospital room charge were calculated based on their usage during the initial hospitalization for each patient. Group comparison was done between the DOB and AMR groups. RESULTS: Length of stay was longer in the DOB group than in the AMR group. Mean calculated cost of intravenous drugs was higher in the DOB group (173,186 +/- 239,147 yen) than in the AMR group (63,145 +/- 47,223 yen, P < 0.05). Total medication costs were higher in the DOB group than in the AMR group. Cost for hospital room charge was higher in the DOB group than in the AMR group. CONCLUSIONS: In the treatment of ADHF, appropriate therapy even with expensive drugs makes total medication costs less expensive comparing with conventional therapy with cheaper drugs during initial hospitalization.

[Protection of amrinone against lung injury induced by ischemia/reperfusion in rats].

OBJECTIVE: To investigate the protective effect of amrinone against experimental lung ischemia /reperfusion (I/R) injury. METHODS: 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. RESULTS: 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. CONCLUSIONS: Amrinone has protections against lung I/R injury, possibly through its anti-oxidation effects and an inhibition of inflammation factors releasing.

[Current approaches to intraoperative diagnosis and treatment of low cardiac output during cardiosurgical operations].

The paper deals with the development of a diagnostic and therapeutic algorithm of intraoperative heart failure during cardiosurgical operations on the basis of evaluation of systolic and diastolic functions of the left and right ventricles. The study included 101 patients with low cardiac output in the postperfusion period. All the patients suffered from coronary heart disease and they underwent myocardial revascularizing operations under extracorporeal circulation. In all the patients, in addition to traditional hemodynamic parameters (heart rate, blood pressure, central venous pressure), the functional status of the left and right ventricles was evaluated by transesophageal Doppler echocardiography (TED echoCG) and the thermodilution technique using a Swan-Ganz catheter having a prompt thermistor. Evaluating the diastolic and diastolic functions of the right and left ventricles makes it possible to identify 2 types of left and right ventricular failure: 1) that due to systolic dysfunction and 2) that due to concomitance of systolic and diastolic dysfunctions. Dobutrex (5-7.5 microg/kg/min) should be used in right ventricular systolic dysfunction. Amrinone (5-10 microg/kg/min) should be given to patients with concomitance of systolic and diastolic dysfunction; in this situation, a combination of dobutrex and nitroglycerin (100-150 ng/kg/min) may be used. The drugs of choice in impaired left ventricular systolic function are epinephrine (30-100 ng/kg/min), dopamine (5-10 microg/kg/min), or dobutrex (5-7.5 microg/kg/min). Their combination with sodium nitroprusside can enhance the efficiency of therapy. In patients with left ventricular failure caused by systolic and diastolic dysfunction, epinephrine, dopamine, or dobutrex may be combined with amrinone (5-10 microg/kg/min) or nitroglycerin (100-150 ng/kg/min).

Proper use of phosphodiesterase inhibitors according to the situations.

We came across a case who because of sustained hypotension with normal cardiac output was given amrinone which offered an initial excellent response but showed impotency later and its replacement by milrinone dramatically improved the hemodynamic status. The ensuing hypotension was thought to be the consequence of the use of amrinone which was given to treat hypotension in conjunction with fluid therapy; besides, it also induced pulmonary hypertension. Therefore, milrinone was given to replace amrinone and was successfully to turn the tide. It is our suggestion that if the use of a phosphodiesterase (PDE) inhibitor is indicated but its side effects are enhanced to refute its use, the application of a different PDE inhibitor should be kept in mind.

Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers.

PURPOSE: The toxic effects and treatment of beta-adrenergic blocker and calcium-channel blocker (CCB) overdose are reviewed. SUMMARY: Overdoses with cardiovascular drugs are associated with significant morbidity and mortality. Beta-blockers and CCBs represent the most important classes of cardiovascular drugs. In overdose, beta-blockers and CCBs have similar presentation and treatment overlaps and are often refractory to standard resuscitation measures. The common feature of beta-blocker toxicity is excessive blockade of the beta-receptors resulting in bradycardia and hypotension. Poisoning by CCBs is characterized by cardiovascular toxicity with hypotension and conduction disturbances, including sinus bradycardia and varying degrees of atrioventricular block. Therapies include beta-agonists, glucagon, and phosphodiesterase inhibitors. However, in beta-blocker poisoning where symptomatic bradycardia and hypotension are present, high-dose glucagon is considered the first-line antidote. Traditionally, antidotes for CCB overdose have included calcium, glucagon, adrenergic drugs, and amrinone. For cases of CCB poisoning where cardiotoxicity is evident, first-line therapy is a combination of calcium and epinephrine; high-dose insulin with supplemental dextrose and potassium therapy (HDIDK) is reserved for refractory cases. Health-system pharmacists should be aware that when these drugs are used as antidotes, higher than normal dosing is needed. CONCLUSION: Poisoning by beta-blockers or CCBs usually produces hypotension and bradycardia, which may be refractory to standard resuscitation measures. For cases of beta-blocker poisoning where symptomatic bradycardia and hypotension are present, high-dose glucagon is considered the first-line antidote. For cases of CCB poisoning where cardiotoxicity is evident, a combination of calcium and epinephrine should be used initially, reserving HDIDK for refractory cases.

Effect of amrinone on mucosal permeability in experimental intestinal ischaemia/reperfusion injury.

BACKGROUND: The preventive effect of amrinone on ischaemia/reperfusion (I/R) injury has been shown in the medical literature. The purpose of the present study was to investigate the preventive effect of amrinone on I/R injury of the small bowel of the rat. METHODS: Thirty-two Wistar albino rats (140-180 g) were divided into four groups (n = 8). In all groups except the sham group the superior mesenteric artery was clamped for 30 min. At the beginning of reperfusion, 1 mL of 2405 Bq/mL 51Cr-ethylenediamine tetra-acetic acid (EDTA) was administered into the prepared ileal segment. Following 30 min of reperfusion, 1 mL of blood was obtained from the portal vein. After the rats were killed, the small intestine was removed for histopathological studies. A total of 5 mg/kg amrinone was administered to the rats in group 1 before ischaemia and in group 2 before reperfusion, whereas only saline was administered to the rats in the control group. Statistical analysis was carried out with Kruskal-Wallis and chi2 test, P < 0.01 was considered significant. RESULTS: Both the blood 51Cr-EDTA measurements (mean +/- SD) and mucosal injury grades (MIG) were highest in the control group (3.95 +/- 0.71 c.p.m.; MIG, 3-5) followed by group 2 (0.50 +/- 0.35 c.p.m.; MIG, 1-3), group 1 (0.47 +/- 0.34 c.p.m. MIG, 0-3), and sham group (0.12 +/- 0.05 c.p.m.; MIG, 0). The difference between groups 1 and 2 and the control group were statistically significant (P < 0.01 for each comparison). The results of group 1 and 2 were similar statistically (P > 0.05). CONCLUSIONS: Amrinone was found to be effective in preventing intestinal I/R injury.

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

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

[Effect of dexamethasone, aminoguanidin, amrinone on oxygen utilization in endotoxin shock rabbits].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: The dexamethasone, aminoguanidin, amrinone can improve oxygen utilization in endotoxic shock rabbits, especially for dexamethasone and aminoguanidin.

[Randomized controlled trial for the effect of amrinone and aprotinin on expression leukocyte adhesion molecule in patients with prosthetic valve replacement during perioperative period].

OBJECTIVE: To explore the effect of amrinone and aprotinin on expression of leukocyte adhesion molecule in patients with prosthetic valve replacement during perioperative period. METHODS: Thirty-two patients undergoing valve replacement were randomized to control group, the first aprotinin group, the second aprotinin group, and amrinone combined with aprotinin group; each group consisted of eight cases. In the first aprotinin group, 3 x 10(6) units of aprotinin was added to the priming solution of the extracorporeal circulation (ECC). In the second aprotinin group, 3 x 10(6) units of aprotinin was added to the priming solution of ECC, which was combined with 1 x 10(6) units of aprotinin for intravenous bolus. In the amrinone combined with aprotinin group, 3 x 10(6) units aprotinin was added to the priming solution of the ECC and amrinone began with a bolus of 1 mg/kg followed by a maintenance intrusion of 8 micrograms/kg.min. The control group received an equivalence without aprotinin. Venous blood samples were drawn before the operation, at the end of the ECC, 1 hour after the end of the ECC, and one day after the operation, respectively. Flow cytometry was used to demonstrate the expression of leukocyte adhesion molecule CD11b/CD18. RESULTS: Before ECC, there were no differences of the levels of CD11b+/CD18+ in all groups (P > 0.05). One hour after the ECC, the level of CD11b+/CD18+ in group B was lower than that in group A, the level of CD11b+/CD18+ in group C was lower than that in group B, and the level of CD11b+/CD18+ in group D was higher than that in group C, but no significant difference between groups was noted (P > 0.05). CONCLUSION: Although amrinone and aprotinin have anti-inflammatory activity, the pump prime which was added aprotinin alone or aprotinin combined with amrinone might fail in preventing the expression of leukocyte adhesion molecule CD11b/CD18 completely in patients with prosthetic valve replacement during ECC perioperative period.

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

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

[Randomized controlled trial for the effect of amrinone and aprotinin on proinflammatory cytokine release in patients with prosthetic valve replacement during perioperative period].

OBJECTIVE: To explore the effect of amrinone and aprotinin on whole-body inflammatory response in the patients with prosthetic valve replacement during perioperative period. METHODS: 24 patients undergoing prosthetic valve replacement were randomized to control group (group A, n = 8), aprotinin group (group B, n = 8) and amrinone combined with aprotinin group (group C, n = 8). In the aprotinin group, 3 x 10(6) of aprotinin was added to the priming solution of the extracorporeal circulation (ECC). In the amrinone combined with aprotinin group 3 x 10(6) of aprotinin was added to the priming solution of the ECC and amrinone began with a bolus of 1 mg/kg followed by a maintenance infusion of 8 micrograms/(kg.min). The control group received an equivalent prime volume without aprotinin. Venous blood samples were drawn before the operation, at the end of ECC, 1 hour after the end of ECC, and one day after the operation respectively. Enzyme-linked immunosorbent assay techniques were used to measure each of the cytokines. RESULTS: Before ECC, there were no differences of the levels of IL-6 and IL-8 among groups (P > 0.05). After ECC, the levels of IL-6 and IL-8 increased significantly in all groups (P < 0.05). The levels on day one after the operation were still higher than those before the operation in all groups (except the level of IL-8 in group C), but no statistical significance was observed. (P > 0.05). At 1 hour after the end of ECC, the level of IL-6 in group B was lower than that in group A, and the level of IL-6 in group C was lower than that in group B, but there was no statistically significant difference (P > 0.05); At the end of ECC, the level of IL-8 in group B was lower than that in group A and the level of IL-8 in group C was lower than that in group B, but no significant difference was noted (P > 0.05). It was also observed that the level of IL-8 was lower in group C than group A or B at 1 hour after the end of ECC. CONCLUSION: Although amrinone and aprotinin have antiinflammatory activity, but pump prime only aprotinin or aprotinin combined with amrinone may fall in preventing proinflammatory cytokine release (IL-6, IL-8) completely in patients with prosthetic valve replacement during ECC perioperative period.

Effects of amrinone on ischaemia-reperfusion injury in cirrhotic patients undergoing hepatectomy: a comparative study with prostaglandin E1.

The effects of amrinone, a selective phosphodiesterase III inhibitor, on liver ischaemia reperfusion injury have not yet been clarified. Forty-five patients with hepatocellular carcinoma who underwent partial liver resection using Pringle's manoeuvre were studied. Patients were divided into three groups: those given amrinone, those given prostaglandin E1 (PGE1) and those not treated (controls). An indocyanine green (ICG) clearance test was performed before the operation and three times during surgery: just before induction of liver ischaemia, just after liver resection and 60 min after reperfusion. Blood lactate and base excess were measured at the same times. Systolic and diastolic arterial pressure, heart rate, cardiac index and oesophageal temperature were monitored. Aminotransferase levels were recorded the day before surgery, 1 h after operation and on the first and third postoperative days. These data were compared between groups. The ICG elimination rate, lactate and base excess in the amrinone group differed significantly from those in controls during the observation period (P = 0.03, P = 0.04 and P = 0.03, respectively). The differences between the PGE1 and control groups were not significant. There were no significant differences between the groups in perioperative vital signs, cardiac index or postoperative aminotransferase. Amrinone enhanced intraoperative ICG elimination in cirrhotic patients who underwent liver resection.

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 microg/kg/min, start 30 minutes before LPS infusion) (amrinone group), or infusion of equivalent volumes of NaCl 0.9% (control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = D(A) 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 D(A) 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 V(E) and D(A) 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.

Prophylactic amrinone for weaning from cardiopulmonary bypass.

This prospective, randomised, double-blind, controlled clinical study was performed at a single tertiary referral centre to test the hypothesis that the prophylactic administration of amrinone before separation of a patient from cardiopulmonary bypass decreases the incidence of failure to wean, and to identify those patients who could be predicted to benefit from such pre-emptive management. Two hundred and thirty-four patients, scheduled to undergo elective cardiac surgery, were randomly allocated to receive either a bolus dose of 1.5 mg x kg(-1) amrinone over 15 min, followed by an infusion of 10 microg x kg(-1) x min(-1), or a bolus of placebo of equal volume followed by an infusion of placebo. Treatment with amrinone or placebo was initiated upon release of the aortic cross-clamp, before weaning from cardiopulmonary bypass. Anaesthetic technique, monitoring and myocardial preservation methods were standardised for both groups. Significantly fewer patients failed to wean in the group that received prophylactic amrinone than in the control group (7 vs. 21%, p = 0.002). Amrinone improved weaning success regardless of left ventricular ejection fraction, although this benefit was statistically significant only in the group with left ventricular ejection fractions > 55%. Of the 32 patients who failed to wean from cardiopulmonary bypass, 14 had normal pre-operative left ventricular ejection fractions.

[Anesthetic management of patients undergoing implantation of left ventricular assist system].

We examined the anesthetic management of six patients with end-stage dilated and hypertrophic cardiomyopathy for implantation of left ventricular assist system. Although anesthesia was induced only with fentanyl or with combination of fentanyl and diazepam, hemodynamic changes after the anesthetic induction were variable and preoperative evaluation of left ventricular ejection fraction did not predict the hemodynamic changes. After the weaning from cardiopulmonary bypass, the right ventricular support by catecholamines, such as dopamine and dobutamine, and phosphodiesterase III inhibitors, such as amrinone, and pulmonary vasodilation by inhalation of nitric oxide were useful to maintain volume loading to the left ventricular assist system.

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

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

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

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

Profound hypoxemia during treatment of low cardiac output after cardiopulmonary bypass.

PURPOSE: To illustrate the multiple causes of hypoxemia to be considered following cardiopulmonary bypass and how therapy given to improve oxygen delivery may have contributed to a decrease in arterial oxygen saturation to life-threatening levels. CLINICAL FEATURES: A 61 yr old man with severe mitral regurgitation and chronic obstructive lung disease underwent surgery for mitral valve repair. A pulmonary artery catheter with the capacity to measure cardiac output and mixed venous oxygen saturation (SvO2) continuously was used. Two unsuccessful attempts were made to repair the valve which was finally replaced, requiring cardiopulmonary bypass of 317 min. Dobutamine 5 micrograms.kg-1.min-1 and sodium nitroprusside 1 microgram.kg-1.min-1 were used to increase cardiac output. Soon after, the SvO2 decreased progressively from 55 to 39%. The patient became cyanotic with a PaO2 of 39 mmHg. Sodium nitroprusside was stopped and amrinone 100 mg bolus followed by 10 micrograms.kg-1.min-1 was given in addition to adding PEEP to the ventilation. With these measures PaO2 could be maintained of safe levels but PEEP and high inspired oxygen concentrations were needed postoperatively until the trachea could be extubated on the third postoperative day. CONCLUSION: The profound hypoxemia in this case was likely due to a combination of intra- and extrapulmonary shunt, both augmented by sodium nitroprusside. The desaturation of mixed venous blood amplified the effect of these shunts in decreasing arterial oxygen saturation. The interaction of these factors are analyzed in this report.

Vesnarinone and amrinone reduce the systemic inflammatory response syndrome.

OBJECTIVE: The systemic inflammatory response is an important cause of organ dysfunction. The present study tested the hypothesis that 2 clinically used agents, amrinone and vesnarinone, would decrease inflammation and cardiac dysfunction in a relevant model of systemic inflammatory response activation. METHODS: Rabbits received intravenous endotoxin, alone or in conjunction with amrinone or vesnarinone. Systemic effects were assessed by death, fever, behavior, and acidosis. Measures of inflammatory signaling were (1) plasma tumor necrosis factor-alpha and interleukin-1 beta production, (2) lung tissue myeloperoxidase activity, and (3) myocardial inducible nitric oxide synthase activity. Indices of systolic and diastolic myocardial function were measured in Langendorff-perfused hearts. RESULTS: Vesnarinone, in particular, reduced mortality rates (19% vs 61% for lipopolysaccharide alone, P =.01) and acidosis in lipopolysaccharide-treated rabbits. Both agents markedly reduced systemic tumor necrosis factor and interleukin-1 concentrations, lipopolysaccharide-mediated effects on myocardial systolic and diastolic function and on myocardial inducible nitric oxide synthase activity. Vesnarinone, but not amrinone, (1) decreased fever and lethargy, consistent with decreased central nervous system effects of endotoxin, and (2) decreased lung leukocyte infiltration. CONCLUSIONS: Vesnarinone and amrinone, which are used clinically for their inotropic and vasodilating properties, may be useful to limit inflammatory activation and consequent organ dysfunction. Structure-activity and/or pharmacokinetic between the compounds may be important, particularly in preventing inflammatory signaling within certain tissues.