Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of the phosphodiesterase inhibitor enoximone for reversal of severe postcardiotomy low cardiac output syndrome was investigated in 13 cases of cardiogenic shock refractory to conventional treatment consisting of beta-adrenergic agonists (n = 13) combined with vasodilators (n = 7), and intra-aortic balloon counterpulsation (n = 5). Following a bolus of 1 mg/kg enoximone, cardiac and stroke volume indices increased from 1.56 +/- 0.27 l/min/m2 and 16.3 +/- 3.3 ml/m2, respectively, to 2.72 +/- 0.67 and 27.8 +/- 7.1 (both p < 0.001). Mean arterial pressure fell, from 77 +/- 11 to 68 +/- 9 mmHg (p < 0.05), as did atrial filling pressures (LAP and RAP), LAP from 21.3 +/- 5.5 to 15.9 +/- 2.9 and RAP from 16.6 +/- 2.3 to 13.7 +/- 2.1 mmHg (both p < 0.01). The heart rate rose by only 5%. Enoximone therapy was maintained by a continuous infusion (5-7.5 micrograms/kg/min) for 40.6 +/- 8.6 hours (range 14-92). All hemodynamic parameters remained stable throughout treatment. Six patients died of sepsis and/or multiorgan failure but seven were discharged from hospital. Enoximone thus improved hemodynamic performance significantly in cardiogenic shock after open-heart surgery. It also has proved valuable in cardiac failure when conventional therapy was unsuccessful.
 ...
PMID:Efficacy of phosphodiesterase inhibitor enoximone in management of postcardiotomy cardiogenic shock. 143 45

Phosphodiesterase III inhibitors have been established in recent years in the therapy of congestive heart failure. Many disadvantages, such as extensive vasodilation and the lack of proven positive inotropic properties combined with thrombepenia and elevation of transaminases, have complicated the handling of the drug in clinical practice. Enoximone, an imidazole derivative, has been demonstrated to be more cardioselective and vasodilation has been found to be less pronounced than with amrinone. As a consequence, research was performed to enhance the cardioselectivity of phosphodiesterase III inhibitors by reduction of non-specific cross-reactivity with other phosphodiesterases, and R80122 (Janssen Pharmaceutics, Belgium) was introduced into clinical practice. R80122 ((E)-Ncyclohexal-N-methyl-2[[[phenyl (1,2,3,5-tetrahydro-2 oxoimidazo [2,1b]-quinazolin-7-yl)methylene] amino] oxy] acetamide) is a selective inhibitor of phosphodiesterase (PDE) IIIc, which is localized in the myocardium. Thus, its inhibition leads to a positive inotropic effect, whereas phosphodiesterase IIIRo is found in the vessel wall and causes vasodilation. This study was performed to investigate the hemodynamic profile of R80122 under clinical conditions. Additionally, the intestinal hemodynamics were recorded and changes in intestinal perfusion compared with changes in global hemodynamics. METHODS. The study was thoroughly discussed and approved by the local ethics committee; all patients gave written informed consent. The investigation was performed on ten male patients who were about to undergo elective coronary artery bypass surgery. History, physical examination and laboratory results were within the normal limits and revealed no evidence of liver disease. The usual medication was continued until the day before the operation. Premedication consisted of 2 mg flunitrazepam p.o. in the evening before the operation and 1.5 h before induction of anaesthesia. The determination of hepatic plasma flow was performed by the indocyanine green (ICG) infusion extraction technique using liver vein catheterization. After induction of anaesthesia (MP1), after application of a bolus dose of R80122 (0.3 mg/kg BW) (MP2) and at sternotomy (MP3), hemodynamic data (heart rate, arterial pressure, cardiac output) were recorded and blood samples for the determination of hepatic plasma flow by the concentration of ICG were collected. Anaesthesia was induced with a bolus dose of 0.2 mg/kg BW etomidate, 7 micrograms/kgBW fentanyl and 0.1 mg/kgBW pancuronium and maintained with a continuous infusion of 20 micrograms/min fentanyl, 300 micrograms/min midazolam and mechanical ventilation with O2/N2O at an FiO2 of 0.5. Statistical analysis was performed using the Wilcoxon-Mann-Whitney U test comparing the results after induction of anesthesia (MPI) with those after application of R80122 (MPII) and the results of MPII with those at sternotomy (MPIII). Statistical significance was assumed at P less than 0.05. RESULTS. After the induction of anaesthesia, the median heart rate (HR) was 56/min and did not change after administration of R80122. During sternotomy there was a significant increase in the HR from 64 to 78/min (P less than 0.05). Median arterial blood pressure (MAP) tended to decreased from 91 mm Hg after induction of 77 mm Hg after administration of R80122, although there was no statistical significance because of interindividual differences in the tendencies. At sternotomy, MAP remained unchanged. Cardiac output (CO) increased by 60% after administration of R80122 (P less than 0.01) and did not change during sternotomy. As a consequence of the changes in HR and CO, stroke volume (SV) increased by 22% after administration of R80122 (P less than 0.025) and decreased to control values during sternotomy.
 ...
PMID:[Effects of R80122. The influence of a new phosphodiesterase inhibitor on global and intestinal hemodynamics in coronary surgery patients]. 152 59

Hemodynamic measurements were done in 42 patients with congestive heart failure of NYHA classes III and IV after administration of the phosphodiesterase inhibitors amrinone und enoximone. Amrinone decreases mean arterial pressure (-4%), right atrial pressure (-39%), and systemic vascular resistance (-23%), while cardiac index and stroke volume index increase to 27% and 26%, respectively; heart rate is nearly unchanged. Enoximone administration in a dose of 1 mg/kg bw produces an increase in cardiac index of 13%, an increase in heart rate of 12%, and a decrease of systemic vascular resistance of 13%, whereas stroke volume index is unchanged. Enoximone in a dose of 1.5 mg/kg bw increases heart rate (+ 9%), cardiac index (+ 33%), and stroke volume index (+ 21%), and decreases systemic vascular resistance (-26%). The hemodynamic profile of amrinone and enoximone in an equal dose shows only slight differences. Furthermore, phosphodiesterase inhibitors produce an increase of cardiac index (+ 19%) and stroke volume index (+ 17%) in patients with pump failure having already received dopamine and dobutamine.
 ...
PMID:[The hemodynamic profile of amrinone and enoximone in patients with severe heart failure]. 183

Enoximone, a new cardiotonic agent not related to glycosides or catecholamines, has been suggested for treatment of low cardiac output syndromes occurring after cardiopulmonary bypass (CPB). The aim of the present study was to compare enoximone with dobutamine in the management of such cases. Twenty consecutive patients who had undergone cardiac surgery with CPB and who had a cardiac index (CI) less than 2.5 l.min-1.m-2, pulmonary capillary wedge pressure greater than 12 mmHg, and no renal failure, were randomly assigned to receive either enoximone (group E, n = 10) or dobutamine (group D, n = 10). The following parameters were monitored at baseline, 15, 30, 60, 90 min, 2, 6, 10 and 14 h: arterial, central venous, pulmonary arterial and capillary wedge pressures (PCWP), cardiac index (CI), stroke volume index (SVI), stroke work index (SWI), systemic (SVR) and pulmonary vascular resistances, as well as heart rate-pressure product (HRPP). Patients in group E were given a bolus of 0.5-1 mg.kg-1 enoximone over a 20 min period, followed by a continuous infusion of 2-20 micrograms.kg-1.min-1, depending on clinical response. In group D, patients were given 2.5 to 15 micrograms.kg-1.min-1 dobutamine according to clinical response. No other inotropic drug was used during the study period. The aim was to obtain an increase in CI greater than or equal to 30% at the end of the first hour of treatment. Excessive systemic hypotension with low SVR was treated with volume loading.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Comparison of enoximone versus tobutamine in the treatment of low cardiac output after cardiac surgery]. 214 89

The aim of this study was to document the effects of enoximone in congestive cardiac failure. The haemodynamic data (aortic pressure, pulmonary pressures, left ventricular pressure, cardiac output, isovolumic contractility index: Vmax) and left ventricular kinetics of 20 patients with dilated cardiomyopathy (11 ischemic and 9 idiopathic in Stages III or IV of the NYHA Classification before recompensation) were recorded under basal conditions, after 30 minutes infusion of dobutamine (10 micrograms/kg/mn) and after 3 hours infusion of enoximone (total dose: 3.6 mg/kg). The two drugs had an equivalent inotropic effect: ejection fraction + 4 +/- 22% with dobutamine and + 16 +/- 39% with enoximone; Vmax increased from 1.53 +/- 0.5 c/sec to 2.49 +/- 0.8 c/sec with dobutamine and to 1.82 +/- 0.5 c/sec with enoximone. Enoximone induced a greater degree of vasodilation (systemic resistances - 14 +/- 21% with dobutamine and - 21 +/- 27% with enoximone) and a more pronounced fall in ventricular filling pressures (- 35 +/- 42% with dobutamine and - 58 +/- 24% with enoximone). Enoximone was less effective than dobutamine in increasing cardiac output (+ 46 +/- 42% with dobutamine and 16 +/- 33% with enoximone) and stroke volume (+ 23 +/- 47% with dobutamine and + 2 +/- 41% with enoximone). This difference in efficacy may be explained by the major reduction in ventricular preload which enoximone induced after that observed with dobutamine. "Responders" (12 patients) had basal cardiac outputs of less than 2.3 l/mn/m2; the peripheral vasodilatation caused by enoximone was greater. Finally, the reduction in left ventricular end diastolic pressure and the increase in Vmax were significantly less in the 11 patients with ischemic cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Enoximone, vasodilator and/or inotropic agent in congestive cardiac insufficiency? Hemodynamic and ventriculographic study of 20 cases]. 214 34

In light of previous studies in adults, we considered that enoximone could be useful in treating children with therapy-resistant cardiovascular insufficiency. Prior to clinical administration, we investigated the cardiovascular properties of enoximone in anesthetized and ventilated piglets characterized by small stroke volume and high heart rate. Enoximone was administered intravenously in increasing doses (0.25, 0.5, and 1 mg/kg). The animals were monitored with heart rate, systemic and pulmonary arterial pressures, and continuous electromagnetic flow. Enoximone induced a dose-dependent flow increase, whereby heart rate and systemic arterial pressure changed only slightly. With regard to persistent pulmonary hypertension in newborns, enoximone was also used in piglets to investigate the effects on endotoxin-induced, dopamine-resistant pulmonary hypertension. Enoximone (1 mg/kg i.v.) was given immediately after E. coli endotoxin (1.5 micrograms/kg i.v.) and inhibited the endotoxin-induced, eicosanoid-mediated pulmonary hypertension, whereas during infusion of dopamine (2 mg/kg/h), no drop in systemic blood pressure could be observed. In the clinical study, six infants with post-cardiac surgery low output syndrome despite maximal catecholamine inotropic support were given enoximone (i.v. bolus of 0.2, 0.5, or 1 mg/kg followed by continuous infusion of 7.5-10 micrograms/kg/min). Continuously measured mixed-venous oxygen saturation increased in a dose-related manner. Cardiac output increased significantly by 28%, accompanied by a decrease of arteriovenous oxygen content difference and O2 utilization ratio. The preliminary results show that intravenous enoximone produces acute useful hemodynamic effects in infants, in particular allowing a weaning of vasoactive amines.
 ...
PMID:Acute hemodynamic response to intravenous enoximone: an animal study and preliminary report in infants after cardiac surgery. 248 Apr 88

Enoximone, a relatively new type III phosphodiesterase (PDE III) inhibitor with combined positive inotropic and vasodilating properties, was used as a pharmacological bridge to heart transplantation in a patient with severe dilatative cardiomyopathy (ejection fraction 11-13%), who developed cardiogenic shock refractory to conventional therapy with catecholamines and vasodilators. Enoximone led to an 88% increase in cardiac index (from 1.6 to 3.0 l/min.m2). Despite a noticeable rise in heart rate, stroke index increased by 57%. Systemic vascular resistance decreased by 48% without any relevant change in mean arterial pressure. Cardiac filling pressures remained high. Oxygen transport doubled and oxygen extraction ratio decreased by 10%. Apart from a decrease in arterial oxygen tension (from 15.8 to 12.8 kPa [119 to 96 mm Hg]), no other side effects were noted. Withdrawal of catecholamine therapy did not cause any relevant haemodynamic changes. Although complications arose from an uncontrolled septic state, orthotopic heart transplantation was performed with success 74 hours after initiation of enoximone therapy. As the PDE III inhibitor enoximone exerts its potent inotropic and vasodilating effects without requiring adrenergic receptor activation, it may be used as an alternative to mechanical support in patients who develop cardiogenic shock resistant to catecholamines while awaiting heart transplantation.
 ...
PMID:[Enoximone as an alternative to mechanical circulatory support prior to heart transplantation]. 252 33

Enoximone possesses both positive inotropic and vasodilatory properties. In heart failure, doses varying between 3 mg/kg and 6 mg/kg produce a beneficial acute hemodynamic response but have been associated with significant side effects. Little is known about the long-term hemodynamic efficacy of this agent. To assess whether a lower dose of enoximone could produce both acute and long-term hemodynamic benefits and be better tolerated, 15 patients with refractory heart failure were given enoximone 100 mg every 8 hours (mean dose, 1.7 mg/kg). The cardiac index, pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, systemic vascular resistance, pulmonary vascular resistance, and stroke volume index all improved significantly during the first 24 hours. The systemic blood pressure and heart rate did not alter appreciably during this period. Five of six patients remaining on therapy at 6 months had a follow-up hemodynamic study. Sustained improvement was seen in the cardiac index, pulmonary capillary wedge pressure, and pulmonary artery pressure when compared to baseline (all p less than 0.05). A satisfactory trend, which did not reach statistical significance, was noted in the right atrial pressure (p = 0.09) and stroke volume index (p = 0.06). Diarrhea occurred in one patient. These findings indicate that enoximone has a beneficial acute and long-term hemodynamic effect at a low dose that is clinically well tolerated.
 ...
PMID:Acute and long-term hemodynamic response to low-dose enoximone in refractory heart failure. 253 57

The peak hemodynamic effect and hormonal response of the phosphodiesterase inhibitor enoximone (MDL 17,043) were compared with those of dobutamine in 10 patients with severe congestive heart failure. Both agents significantly (p less than 0.05) increased cardiac index, stroke volume index and heart rate. Enoximone tended to decrease mean systemic arterial and pulmonary artery wedge pressures (0.05 less than p less than 0.1), whereas dobutamine did not. Both agents decreased systemic vascular resistance (p less than 0.05). The increase in heart rate was greater with dobutamine than with enoximone (p less than 0.05). Plasma renin activity increased significantly with dobutamine (from 11.3 +/- 13.5 to 17.8 +/- 15.0 ng/ml/hour, p less than 0.01) and with enoximone (from 13.6 +/- 18.3 to 16.6 +/- 18.8 ng/ml/hour, 0.05 less than p less than 0.1). Dobutamine suppressed plasma norepinephrine level (p less than 0.05) and enoximone did not. Neither agent affected the plasma vasopressin level. These data demonstrate a similar acute hemodynamic and hormonal profile for both enoximone and dobutamine. Further, dobutamine, like other beta agonists, provokes renin secretion and may do so to a greater extent than enoximone.
 ...
PMID:Comparative hemodynamic and hormonal response of enoximone and dobutamine in severe congestive heart failure. 294 27

Enoximone, a phosphodiesterase inhibitor, is a potent inotropic vasodilator agent that causes a marked improvement in systemic hemodynamics in patients with severe chronic congestive heart failure. Cardiac index, stroke volume index and stroke work index increase, and there is a significant decrease in pulmonary capillary wedge pressure. Left ventricular dP/dt increases, despite a decrease in arterial pressure and systemic vascular resistance and without any significant change in heart rate, indicating a positive inotropic effect. A marked decrease in systemic vascular resistance indicates that decreased left ventricular outflow resistance resulting from peripheral vasodilation also contributes to improvement in left ventricular function. In some patients, left ventricular end-diastolic volume increases despite a marked decrease in pulmonary capillary wedge pressure, suggesting an improvement in apparent left ventricular compliance, which may also be contributory to improved left ventricular function.
 ...
PMID:Potential mechanisms of improved left ventricular function with enoximone in severe congestive heart failure. 295 66


1 2 Next >>