Enoximone echocardiography for predicting recovery of left ventricular dysfunction after revascularization : a novel test for detecting myocardial viability.
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BACKGROUND: The possibility that enoximone, a nonglycoside, noncatechol, positive inotropic agent, in combination with 2-dimensional echocardiography may predict recovery of myocardial dysfunction after revascularization has not been yet evaluated. METHODS AND RESULTS: Forty-five patients with chronic coronary artery disease and left ventricular dysfunction underwent dobutamine (DE, 5 to 10 microg. kg(-1). min(-1)) and enoximone (EE, 1.5 mg/kg, over 10 minutes) echocardiography. Myocardial wall motion was scored from 1 (normal) to 4 (dyskinesia): an asynergic segment was considered to have contractile enhancement when the score decreased by >/=1 grade. Of 478 asynergic segments, 216 (45%) exhibited functional recovery after revascularization. Dobutamine- and enoximone-induced contractile enhancement was observed in 41% and 46% of segments, respectively. Compared with DE, EE had higher sensitivity (88% versus 79%, P<0.01) and negative predictive value (90% versus 84%, P<0.05) in predicting functional recovery. The specificity (89% versus 90%) and positive predictive value (87% for both EE and DE) were similar. Concordant interpretation of EE and DE findings was found in 85% (406 of 478) of affected segments. Prerevascularization coronary angiography showed that stenosis severity of vessels supplying areas which only improved with enoximone was significantly greater (89.9%) than that of vessels (77.7%) supplying areas that responded to both agents (P<0.02). Both dobutamine and enoximone increased heart rate (16% and 10%, respectively), whereas enoximone did not cause changes in systolic blood pressure that increased by 14% with dobutamine. CONCLUSIONS: Enoximone echocardiography provides a novel and reliable approach for the prediction of functional recovery after revascularization. Compared with dobutamine echocardiography, the test yields higher sensitivity and induces lesser hemodynamic alterations. (+info)
Low-dose enoximone improves exercise capacity in chronic heart failure. Enoximone Study Group.
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OBJECTIVES: This study was designed to evaluate the effects of low-dose enoximone on exercise capacity. BACKGROUND: At higher doses the phosphodiesterase inhibitor, enoximone, has been shown to increase exercise capacity and decrease symptoms in heart failure patients but also to increase mortality. The effects of lower doses of enoximone on exercise capacity and adverse events have not been evaluated. METHODS: This is a prospective, double-blind, placebo-controlled, multicenter trial (nine U.S. centers) conducted in 105 patients with New York Heart Association class II to III, ischemic or nonischemic chronic heart failure (CHF). Patients were randomized to placebo or enoximone at 25 or 50 mg orally three times a day. Treadmill maximal exercise testing was done at baseline and after 4, 8 and 12 weeks of treatment, using a modified Naughton protocol. Patients were also evaluated for changes in quality of life and for increased arrhythmias by Holter monitoring. RESULTS: By the protocol-specified method of statistical analysis (the last observation carried-forward method), enoximone at 50 mg three times a day improved exercise capacity by 117 s at 12 weeks (p = 0.003). Enoximone at 25 mg three times a day also improved exercise capacity at 12 weeks by 115 s (p = 0.013). No increases in ventricular arrhythmias were noted. There were four deaths in the placebo group and 2 and 0 deaths in the enoximone 25 mg three times a day and enoximone 50 mg three times a day groups, respectively. Effects on degree of dyspnea and patient and physician assessments of clinical status favored the enoximone groups. CONCLUSIONS: Twelve weeks of treatment with low-dose enoximone improves exercise capacity in patients with CHF, without increasing adverse events. (+info)
Enoximone pharmacokinetics in infants.
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Enoximone and enoximone sulphoxide concentrations were measured in plasma of 20 infants, median age 6.0 (range 0.6-49.7) weeks, during and after prolonged continuous infusions. Patients were given enoximone 1 mg kg-1 and an infusion at 10 micrograms kg-1 min-1 just before being weaned from cardiopulmonary bypass (CPB). The infusion was stopped when clinically indicated, after a median 97 (range 24-572) h. Arterial blood samples were taken 30 min and 12 h after CPB, every 24 h during the infusion, and then 2, 4, 8, 12 and 24 h after the infusion was stopped. Pharmacokinetic non-compartmental analysis was performed using TOPFIT software. Fourteen patients who retained normal hepatic function had a median (95% confidence intervals) clearance of 9.7 (6.3-14.1) ml min-1 kg-1, elimination half-life of 5.2 (2.4-6.8) h and a volume of distribution of 3.6 (2.0-5.7) litre kg-1. The six patients with significant hepatic dysfunction had a lower clearance, 5.7 (2.4-14.5) ml min-1 kg-1, and significantly longer elimination half-life, 7.6 (6.5-10.9) h (P = 0.02). Enoximone sulphoxide elimination half-life was significantly prolonged in three patients with renal dysfunction, 16.2 (10.5-17.7) h versus 6.9 (6.1-9.4) h (P = 0.03). These results confirm that enoximone pharmacokinetics in infants is similar to that found in adults. The infusion rate of enoximone should be reduced if hepatic or renal dysfunction supervenes. (+info)
Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: a randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol.
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OBJECTIVE: We compared the hemodynamic effects of dobutamine and enoximone administration before and after long-term beta-blocker therapy with metoprolol or carvedilol in patients with chronic heart failure (HF). BACKGROUND: Patients with HF on beta-blocker therapy may need hemodynamic support with inotropic agents, and the hemodynamic response may be influenced by both the inotropic agent and the beta-blocker used. METHODS: The hemodynamic effects of dobutamine (5 to 20 microg/kg/min intravenously) and enoximone (0.5 to 2 mg/kg intravenously) were assessed by pulmonary artery catheterization in 29 patients with chronic HF before and after 9 to 12 months of treatment with metoprolol or carvedilol at standard target maintenance oral doses. Hemodynamic studies were performed after >/=12 h of wash-out from all cardiovascular medications, except the beta-blockers that were administered 3 h before the second study. RESULTS: Compared with before beta-blocker therapy, metoprolol treatment decreased the magnitude of mean pulmonary artery pressure (PAP) and pulmonary wedge pressure (PWP) decline during dobutamine infusion and increased the cardiac index (CI) and stroke volume index (SVI) response to enoximone administration, without any effect on other hemodynamic parameters. Carvedilol treatment abolished the increase in heart rate, SVI, and CI and caused a rise, rather than a decline, in PAP, PWP, systemic vascular resistance, and pulmonary vascular resistance during dobutamine infusion. The hemodynamic response to enoximone, however, was maintained or enhanced in the presence of carvedilol. CONCLUSIONS: In contrast with its effects on enoximone, carvedilol and, to a lesser extent, metoprolol treatment may significantly inhibit the favorable hemodynamic response to dobutamine. No such beta-blocker-related attenuation of hemodynamic effects occurs with enoximone. (+info)
Incidence and risk calculation of inotropic support in patients undergoing cardiac surgery with cardiopulmonary bypass using an automated anaesthesia record-keeping system.
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BACKGROUND: This retrospective study analysed the effects of preoperative and intraoperative factors on the occurrence of inotropic support after cardiopulmonary bypass (CPB). METHODS: The data sets of 1471 adult patients having received elective cardiac surgery with CPB were recorded using an online anaesthesia record-keeping system. Patients were judged to have required inotropic drug support if they had received one or a combination of the positive inotropic drugs, epinephrine, dobutamine and enoximone. The effects of age, height, weight, body mass index, gender, chronic heart failure, documented preoperative myocardial infarction, left main coronary artery disease, preoperative history of hypertension, chronic renal failure, diabetes mellitus, chronic obstructive pulmonary disease (COPD), preoperative medical treatment, type of surgical procedure, duration of CPB, duration of aortic clamping and reperfusion time were analysed by logistic regression for predictive power of the need for positive inotropic drugs. RESULTS: Of the patients, 32.4% received positive inotropic drugs in the operating theatre after weaning from CPB. The overall 30-day mortality was 2.2%. Of non-survivors, 81.8% received inotropes compared with 18.2% of survivors (P < 0.01). The numbers of previous myocardial infarctions (odds ratio (OR), 2.01), congestive heart failures New York Heart Association class > 2 (OR, 1.85), COPD (OR, 1.85) and age > 65 yr (OR, 1.62), aortic cross clamping time of > 90 min (OR, 2.32) and coronary artery bypass surgery (OR, 0.43) all represented influential factors within the logistic regression model. CONCLUSION: The knowledge of these risk factors should be useful in increasing the anaesthetist's vigilance in those patients most at risk for inotropic support and in providing for more timely therapeutic intervention and optimizing anaesthesia management. (+info)
In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine.
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BACKGROUND: In human skeletal muscles, the phosphodiesterase-III inhibitor enoximone induces in vitro contracture development, and it has been suggested that enoximone could trigger malignant hyperthermia (MH). In this study, the in vitro and in vivo effects of enoximone in MH-normal (MHN) and MH-susceptible (MHS) swine were investigated. METHODS: Malignant hyperthermia trigger-free general anesthesia was performed in MHS and MHN swine. Skeletal muscle specimens were excised for an in vitro contracture test with 0.6 mm enoximone. Thereafter, MHS and MHN swine were exposed to cumulative administration of 0.5, 1, 2, 4, 8, 16, and 32 mg/kg enoximone intravenously. Clinical occurrence of MH was defined by a Pco(2) greater than 70 mmHg, a pH less than 7.20, and an increase in body temperature of more than 2.0 degrees C. RESULTS: Enoximone induced marked contractures in all MHS muscle specimens in vitro. In contrast, only small or no contracture development was observed in MHN muscle specimens, without an overlap in contractures between MHS and MHN muscles. However, in vivo, no clinical differences were found between MHS and MHN swine following cumulative enoximone doses. According to the defined criteria, none of the swine developed MH during the experiment. Furthermore, high enoximone doses induced progressive circulatory insufficiency, and after receiving 32 mg/kg enoximone, all animals died of cardiovascular failure. CONCLUSIONS: The cumulative enoximone doses used in this study were 30- to 50-fold higher than therapeutic doses in humans. Enoximone does not trigger MH in genetically determined swine. However, enoximone might be useful for in vitro diagnosis of MH. (+info)
Circulatory effects of the PDE-inhibitors piroximone and enoximone.
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1. The isolated circulatory response to intravenous application of the phosphodiesterase (PDE) inhibitors piroximone and enoximone was studied. 2. In a randomized sequence of 30 male patients undergoing elective aortocoronary bypass grafting either piroximone (0.5 mg kg(-1); n = 10) or enoximone (0.5 mg kg(-1); n = 10) were given during steady state of cardiopulmonary bypass (CPB). A group in which NaCl was given as a placebo served as a control (n = 10). 3. MAP was reduced by piroximone (maximum -23 mm Hg) and enoximone (maximum -18 mm Hg), whereas it increased in the control (+20 mm Hg). Volume of the extracorporeal circuit indicating venous pooling decreased more pronouncedly in the enoximone patients (-440 ml) than in the piroximone group (-300 ml). 4. Laser Doppler flows (LDFs) increased in both PDE-III inhibitor groups with the higher and longer increase in the enoximone-treated patients (LDF-forehead maximum +44%, LDF-forearm maximum +33%). Piroximone-induced increase in both LDFs was less pronounced with respect to both time and degree (LDF-forehead maximum +30%, LDF-forearm +12%). 5. Oxygen consumption (VO2) was significantly higher in the PDE-III inhibitor-treated than in the control patients. 6. Piroximone and enoximone showed significant vasodilatory properties at the arterial and venous side (= 'venous pooling'), from which patients with heart failure would profit. 7. Vasodilation could be observed for a longer period and was more pronounced in the enoximone-treated than in the piroximone patients. Alterations in capillary skin blood flow measured by laser Doppler technique gave evidence for an improvement in nutritive microcirculation, which was slightly more pronounced in the enoximone patients. (+info)
Enoximone echocardiography: a novel test to evaluate left ventricular contractile reserve in patients with heart failure on chronic beta-blocker therapy.
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BACKGROUND: It has been suggested that an extensive contractile reserve identified recognised by means of dobutamine stress echocardiography may predict a better prognosis in patients with severe left ventricular dysfunction at rest. However, the clinical use of dobutamine stress echocardiography may be limited in patients with chronic heart failure by the substantial proportion of such patients treated with beta-blockers, since the inotropic response to adrenergic stimulation is known to be attenuated in patients receiving beta-adrenoceptor blockers. Enoximone is a positive inotropic agent that inhibits cyclic adenosine monophosphate-specific phosphosdiesterase. We therefore tested the hypothesis that enoximone may be an alternative to dobutamine in evaluating left ventricular contractile reserve in patients with systolic dysfunction on chronic beta-blocker therapy. METHODS: We studied 26 patients (21 males and five females) with a mean age of 58 PlusMinus; 10 years: 11 were not receiving beta-blockers (noBB group); 15 were receiving carvedilol at a mean dose of 34 mg/day (BB group). Dobutamine was infused at doses of 5 and 10 micrograms/kg/min, and enoximone at a dose of 1.5 mg/kg. RESULTS: The ejection fraction in the noBB group increased by 9% with dobutamine and 8.73% with enoximone (p = 0.86); in the BB group, it increased by 6% with dobutamine and 8.94% with enoximone (p = 0.03). Regional peak systolic velocities were evaluated by means of tissue Doppler imaging in four basal and four medium level segments. In the noBB group, they increased more with dobutamine than with enoximone in three of the eight segments; no significant differences were found in the BB group. Dobutamine induced non-sustained ventricular tachycardia in three patients and supraventricular tachycardia in one, whereas enoximone did not induce any repetitive arrhythmias. CONCLUSIONS: Enoximone might be preferable to low-dose dobutamine for evaluating left ventricular contractile reserve in chronically beta-blocked heart failure patients as it is slightly more potent and has a better safety profile. (+info)