Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the risk of ischemia in 17 patients with significant coronary artery disease, the influence of enoximone was analyzed under the following conditions: (1) at rest (RC) and during exercise (ExC) under control conditions and (2) at rest (RE) and during exercise (ExE) after administration of enoximone (0.75 mg/kg, intravenously). During ExC all patients had ischemia (angina, and ST segment alterations); metabolic markers of ischemia (MMI) increased, as did the mean pulmonary artery pressure, from 19 to 41 mm Hg. However, during ExE ischemia was abolished (no angina, decrease in mean pulmonary artery pressure to 24 mm Hg, and improvement in MMI) and there was some improvement in left ventricular pump function, whereas pre- and afterload decreased (pulmonary artery pressure by 40%, systemic vascular resistance by 10%), and heart rate, arterial pressure, and myocardial oxygen consumption (MVO2) were all unchanged (p greater than 0.05). Comparative hemodynamics at RE vs RC showed a decrease in pulmonary artery pressure (by 25%) and pulmonary vascular resistance (by 19%) and an increase in heart rate (by 11%), whereas arterial pressure and MVO2 were unchanged (p greater than 0.05). Enoximone did not induce changes in plasma catecholamine, prostaglandin, or thromboxane levels (p greater than 0.05), whereas the atrial natriuretic factor decreased (by 15%), probably because of unloading of the atria during exercise. We concluded that enoximone induces beneficial hemodynamic effects in coronary artery disease without causing ischemia, probably by enhancing myocardial contractility, vasodilation, and improved diastolic properties.
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PMID:Hemodynamic, antiischemic, and neurohumoral effects of enoximone in patients with coronary artery disease. 256 85

The phosphodiesterase inhibitor enoximone has both vasodilating and positive inotropic pharmacological properties. The balance between vasodilation and positive inotropism may be different between the various types of heart failure as well as the various stages of heart failure. Therefore, we investigated the effect of intravenous application of enoximone (1 mg/kg body weight) in a cohort of patients (n = 10) suffering from acute or subacute heart failure mainly due to ischemia or hypoxia. All patients had high left ventricular filling pressure, low cardiac output and were pretreated with intravenous dobutamine. Enoximone increased cardiac output from 3.2 +/- 1.2 to 5.5 +/- 2.2 l/min, increased heart rate from 94 +/- 20 to 100 +/- 18 beats/min, decreased systemic peripheral resistance from 1770 +/- 861 to 931 +/- 340 dyn.sec.cm-5 and decreased pulmonary wedge pressure from 24 +/- 5 to 20 +/- 6 mmHg, significantly. However, systolic aortic pressure, systolic pulmonary pressure and right atrial pressure were not significantly altered. We conclude that in a selected group of patients enoximone-given intravenously and acutely in the intensive care unity-can induce beneficial effects on central hemodynamics without critical falls in perfusion pressure.
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PMID:[Use of enoximone in patients with acute and subacute heart failure in the intensive care unit]. 809 21

When enoximone is acutely administered to patients with stable angina and angiographically proven relevant coronary stenosis i.v. application of 0.75 mg/kg exhibits pronounced antiischemic effects. This could be observed in patients during exercise and in those in whom the ischemia was provoked by rapid cardiac stimulation. The antiischemic effects were documented by relief of symptoms, reduction of ST-depression, improvement of impaired myocardial wall motion, decrease to normalization of pathologically elevated filling pressure, amelioration of coronary blood flow as evidenced by myocard scintigraphy and washout time of an intracoronarily injected echo-contrast medium. There was also a definite improvement of ischemia-caused mitral regurgitation. Similar observations were found when the drug was injected in the diseased coronary arteries in a small dose (0.075 mg/kg) so that peripheral effects were not present. In comparison to the Ca(++)-blocker Gallopamil the antiischemic effects of Enoximone were more pronounced, a synergistic action was, however, observed. Negative dromotropic effects of Gallopamil could be abolished by Enoximone. With oral administration of the drug over a period of one week antiischemic effects could also be documented with Holter monitoring as well as during exercise. There was a reduction of ST-depression both at spontaneously occurring ischemic episodes and during exercise, in the number and duration of episodes of silent ischemia, particularly, however, a decrease in symptomatic episodes. In none of the patients under study proarrhythmic effects were observed.
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PMID:[The anti-ischemic effect of phosphodiesterase III inhibitors]. 809 22

It has been clearly established that ischemic heart disease, hypertension and ageing affect diastolic function before any change is observed in contractile function. Though an increasingly recognised clinical entity, cardiac failure with normal systolic function still does not have any specific treatment. Phosphodiesterase inhibitors which increase AMPc, in addition to their inotropic and vasodilator effects, accelerate relaxation. Major and isolated abnormalities of relaxation have been demonstrated in vitro in non necrosed tissues of both the dilated and hypertrophic forms of advanced cardiomyopathy. The myocardium seems unable to restore rapidly the low cytosolic calcium concentrations required for the deactivation of the contractile proteins. The underlying mechanisms are probably very complex but a deficit in AMPc production has been demonstrated in very advanced stages of cardiomyopathy. In ischemia, however, the abnormalities of relaxation seem to be directly related to a defect in free energy production inhibiting the sarcoplasmic reticulum calcium pump. If abnormalities of relaxation due to ischemia and those due essentially to a passive mechanism are excluded, phosphodiesterase inhibitors would seem to have pharmacological effects likely to improve diastolic function. Clinical studies confirm the beneficial effects of Milrinone and Enoximone on relaxation and the rapid phase of diastolic filling, both in acute and chronic studies. However, it has not yet been clearly established whether improved diastolic function is due to a direct action on the myocardium or an indirect action due to improved conditions of load. In order to determine the specific effects of phosphodiesterase inhibitors on diastolic function, further research is required.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of phosphodiesterase inhibitors on diastolic function]. 821 93

The influence of intracoronary enoximone at a dose of 0.075 mg/ kg/10 min on global and regional wall motion and myocardial perfusion (Group I, n = 10) as well as on diastolic LV function (Group II, n = 8) during pacing-induced ischemia was investigated in 18 patients with significant LAD stenoses. The hemodynamic parameters were determined by left heart catheterization, the systolic and diastolic left ventricular function by echocardiography including Doppler technique, and myocardial perfusion analysis was done after intracoronary application of contrast medium. Enoximone did not change either heart rate (79 +/- 9 vs 80 +/- 9 min-1) or blood pressure (LVSP: 159 +/- 7 vs 162 +/- 5 mm Hg) at rest. In the postpacing ischemic period after enoximone, LVEDP fell from a mean of 28.9 to 18.4 mm Hg (p < 0.001), dp/dtmax increased from 1050 to 1369 mm Hg/s (p < 0.001) and regional EF from 47% to 58% (p < 0.01), while global EF remained unchanged (45% vs 47%). ST-segment depression was reduced significantly from 2.3 to 1.5 mm (p < 0.01). Enoximone induced an increase in myocardial perfusion by 129% (p < 0.001) in the stenosis-dependent myocardial areas with shortening of the wash-out half-life time of the echo contrast medium from a mean of 14 s to 5 s (p < 0.001). The isovolumetric relaxation was shortened by 13% (p < 0.05), the E wave by 5%, and dp/dtmin increased by 17% (p < 0.01). In summary, intracoronary application of enoximone led to an improvement in both systolic and diastolic LV function without concomitant peripheral effect due to regression of myocardial ischemia.
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PMID:[Acute effects of enoximone after intracoronary administration on hemodynamics, myocardial perfusion and regional wall motion]. 906 48

Sequestration of activated PMN and enrichment in tissues play a key role in tissue damage during septicaemia and after ischemia/reperfusion. Since polymorphonuclear neutrophilic granulocytes (PMN) of term neonates show various functional differences compared to PMN in adults (decreased chemotaxis, decreased intracellular killing, decreased adhesion) we studied the influence of interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) on the reduction of deformability of PMN in neonates and adults. The following phosphodiesterase (PDE)-inhibitors were applied to ameliorate the reduction in deformability when the PMN were stimulated with fMLP or IL-8: Enoximone, Milrinone (PDE-III-inhibitors), Pentoxifylline (PTX) and Piclamilast (PDE-IV-inhibitors). The micropipette technique and the cell transit analyzer (CTA) were used and compared. Aspiration times into micropipettes with an internal diameter of 5 microm, transit times through 8 microm filter pores and neutrophil elastase concentrations were determined. Despite of the functional differences of PMN in neonates compared to adults the significant decrease of deformability of PMN activated with cytokines compared to passive PMN was not different in both groups. The neutrophil elastase concentrations reflect the activation of the PMN: highest concentrations during activation, decreased concentrations due to PDE-inhibitors, and PMN in a passive state. The neutrophil elastase concentrations were not different from PMN of neonates and adults. These PDE-inhibitors significantly increased the deformability of activated PMN but significant differences between the deformability of PMN in neonates and adults were not found. Despite the functional differences of PMN in neonates PDE-III/IV-inhibitors lead to similar improvement of mechanical properties of activated PMN in neonates and adults. These drugs may ameliorate impaired microcirculation also in neonates during inflammation.
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PMID:Effects of phosphodiesterase (III/IV)-inhibitors and cytokines on mechanical properties of neutrophilic granulocytes in neonates and adults. 2067 13