Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.1.6 (CAD)
4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The beta-blocker carvedilol has been shown to induce vasodilation in patients with coronary artery disease. In a double-blind, randomized, placebo-controlled cross-over study, we looked for the acute vasodilating effect after i.v. administration in patients with heart failure. In 10 patients with coronary artery disease and six patients with dilated cardiomyopathy, all with an ejection fraction lower than 40%, the rate-pressure-product during supine ergometry and Swan-Ganz-catheterization rose to a significantly smaller extent after 5 mg carvedilol i.v. compared to placebo. This was mainly due to a lower heart rate at rest and during exercise, while blood pressure was not changed compared to placebo. Calculated total peripheral resistance during exercise after carvedilol was higher--significantly so in the CAD-group--than after placebo. These results show that in patients with heart failure, an acute vasodilating effect of i.v. carvedilol is not detectable.
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PMID:[Acute hemodynamic effects of the vasodilator beta blocker carvedilol in heart failure]. 197

Biochemical analyses from endomyocardial biopsies indicate that cardiac energy metabolism is altered in patients with end-stage cardiac failure. Myocardial energy production is predominantly based on fatty acid oxidation. Carnitine, a naturally occurring compound, plays an essential role in fatty acid oxidation by carrying long-chain fatty acids into the mitochondrial matrix where they undergo beta-oxidation. In experimental animals, myocardial carnitine deficiency may cause cardiomyopathies which are reversible with carnitine substitution. Rare human diseases, as systemic carnitine deficiency, are associated with impaired cardiac function. We therefore investigated carnitine metabolism in patients with cardiac failure. Plasma and myocardial carnitine levels were measured in 55 patients undergoing cardiac transplantation because of end-stage cardiac failure based on dilated cardiomyopathy (DC, n = 30) or coronary artery disease (CAD, n = 22). Elevated plasma carnitine levels (controls: 49 +/- 12 microM; DC: 82 +/- 38 microM; p less than 0.001, CAD: 86.9 +/- 21.6 microM; p less than 0.05) were found in both patient groups (Fig. 1). Plasma carnitine did not correlate with creatinine (Fig. 2). Compared to controls, myocardial carnitine levels were significantly reduced: DC: 5.9 +/- 1.45 nmol/mg NCP; CAD: 5.84 +/- 1.84 nmol/mg NCP; controls: 15.6 +/- 5.4 nmol/mg NCP (Fig. 3). No correlation between myocardial and plasma levels was found (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Carnitine metabolism--changes in the end stage of dilated cardiomyopathy and ischemic heart muscle disease]. 332 28

The relation between ventricular premature beats (VPBs) and physiologic disease was investigated in 305 patients who had 24-hour Holter monitoring tests, cardiac catheterization and angiography. Both frequency and Lown class of VPBs were measured. Analyses showed that occurrence of VPBs at an average frequency of more than 2 per hour or occurrence of complex VPBs (Lown class greater than 2) have the highest association with the presence and severity of cardiac disease. Using these criteria, VPB severity was then compared with extent of ventricular wall motion abnormality (right anterior oblique projection segments), ejection fraction, end-diastolic pressure, category of disease (normal, coronary artery disease [CAD], valvular heart disease, dilated cardiomyopathy), age and severity of CAD (major coronary arteries with greater than 75% diameter reduction). Severe VPBs defined either by complexity or frequency were significantly correlated with extent of wall motion abnormality, ejection fraction, category of disease and age. Severe VPBs were not significantly correlated with end-diastolic pressure or severity of CAD. Discriminant analysis then showed that in addition to wall motion abnormality and ejection fraction, category of disease and age are independently correlated with VPB severity.
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PMID:Relation of ventricular premature beats to underlying heart disease. 670 27

The regulation of cytosolic Ca2+ concentration during excitation-contraction coupling is altered in the failing human heart. Previous studies have focused on disturbances in Ca2+ release and reuptake from the sarcoplasmic reticulum (SR), whereas functional studies of the cardiac Na(+)-Ca2+ exchanger, another important determinant of myocyte homeostasis, are lacking for the failing human heart. Using a cardiac Na(+)-Ca2+ exchanger cDNA recently cloned from a guinea pig cDNA library, we investigated the gene expression of the cardiac Na(+)-Ca2+ exchanger in relation to the SR Ca(2+)-ATPase. Expression of both genes was quantified in left ventricular myocardium from 24 failing human cardiac explants and 7 control heart samples in relation to beta-myosin heavy chain mRNA by slot blot analysis. Compared with patients with nonfailing hearts, patients with dilated cardiomyopathy (DCM, n = 13) showed a 55% increase in Na(+)-Ca2+ exchanger mRNA levels (P < .05 versus control value) and a 41% increase in patients with coronary artery disease (CAD, n = 11). In the same hearts, SR Ca(2+)-ATPase mRNA levels were decreased by 50% in DCM and by 45% in CAD (P < .05 for both versus control value). There was a positive correlation between Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase mRNA levels both in normal and failing human hearts, albeit with different slopes and intercepts of the regression line. The Na(+)-Ca2+ exchanger protein levels as assessed by Western blot analysis and normalized to beta-myosin heavy chain protein were increased in DCM and CAD (P < .05 and P < .01 versus control value, respectively), whereas SR Ca(2+)-ATPase protein levels were reduced (P < .05 for both groups versus control values). Thus, the Na(+)-Ca2+ exchanger gene expression is enhanced in failing human hearts and may, in part, compensate for the depressed SR function with regard to diastolic Ca2+ removal.
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PMID:Gene expression of the cardiac Na(+)-Ca2+ exchanger in end-stage human heart failure. 806 18

Coronary flow reserve was studied in patients with dilated cardiomyopathy. A 3F coronary Doppler catheter was placed in the proximal left anterior descending artery in each of 10 patients with dilated cardiomyopathy (CDM group), seven patients with coronary artery disease that involved only the left anterior descending artery (CAD group), and seven patients with chest pain syndrome and normal hearts (control group). Coronary flow reserve was calculated as the ratio of the maximum mean coronary blood flow velocity after intracoronary administration of papaverine (10 mg) to resting flow velocity (M/R). The time until maximum flow velocity was reached after papaverine administration (Tmax) was also measured. M/R was lower in the DCM (p < 0.001) and CAD (p < 0.001) groups when compared with the control group. Tmax was not abnormal in the DCM group but was prolonged in the CAD group (p < 0.05). In the DCM group, the M/R ratio correlated with the left ventricular end-diastolic pressure (r = -0.69; p < 0.05), the left ventricular end-diastolic volume index (r = -0.7; p < 0.05), the ejection fraction (r = 0.82; p < 0.01), the left ventricular mass (r = -0.7; p < 0.05), and the left ventricular end-diastolic wall stress (r = -0.84; p < 0.001). These results indicate that coronary flow reserve was decreased in patients with dilated cardiomyopathy and that the mechanism of its reduction may differ from that in patients with coronary artery disease.
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PMID:Coronary flow reserve in patients with dilated cardiomyopathy. 841 48

Two case control studies were performed to evaluate whether smoking may affect myocardial function. Cardiomyopathy subjects had a greater pack year smoking history than 52 control subjects with no CAD (p < 0.02) and were more likely to have diabetes (p < 0.10), but they did not differ from controls with respect to age, alcohol intake, or the presence of hypertension. The risk of cardiomyopathy doubled with an increase of 39 pack years. Smoking history was not related to ejection for fraction for subjects with severe coronary artery disease. These results suggest that smoking may be an important risk factor for idiopathic congestive cardiomyopathy.
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PMID:Smoking and idiopathic congestive cardiomyopathy. 877 33

Dobutamine stress echocardiography was performed in 56 consecutive patients, mean age: sixty-two +/- twelve years. Twenty-two patients had an idiopathic dilated cardiomyopathy (group 1) and 34 had angiographically proven ischemic dilated cardiomyopathy (group 2). Wall motion score index and left ventricular ejection fraction were determined at baseline, 5 micrograms/kg/min, peak, and ten minutes after stepwise dobutamine infusion. Worsening or no change in global wall motion score was observed in 9 group 2 patients (26%) and 1 group 1 patient (5%, P = .07). No significant difference was observed with regard to wall motion score index decrease between baseline and peak dose. Left ventricular ejection fraction increase during dobutamine infusion was comparable in both groups. Thus, an ischemic response was observed more often in the coronary artery disease group, yielding a good specificity and positive predictive value although sensitivity was low. However, left ventricular function improvement did not help to discriminate patients with or without significant CAD.
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PMID:Is dobutamine stress echocardiography useful for noninvasive differentiation of ischemic from idiopathic dilated cardiomyopathy? 931 28

Overproduction of the potent vasoconstrictor peptide endothelin-1 (ET-1) is implicated in the pathogenesis of coronary artery disease. In endothelium-denuded human coronary arteries the response to big ET-1 was significantly enhanced in atherosclerotic arteries (coronary artery disease, CAD; n=7) with an EC50 value of 96 nM (57- 161 nM, 95% C.I.) compared to 274 nM (205-365 nM) in non-diseased arteries (dilated cardiomyopathy, DCM; n=10) (Mann-Whitney U-test, P<0.05). Higher levels of immunoreactive endothelin (ET) could be detected by radioimmunoassay in bathing medium taken from CAD arteries than from DCM arteries (2.8+/-0.5 nM, n=5 vs 1.1+/-0.2 nM, n=7) (Student's two-tailed t-test, P<0.05). There were no differences in responses of arteries from either group to ET-1 (EC50 10 nM, CAD vs 14 nM, DCM). The enhanced response of atherosclerotic human coronary arteries to big ET-1 appears to be due to up-regulation of endothelin-converting enzyme (ECE) activity rather than to an augmented response of the arteries to ET-1. This non-endothelial ECE may therefore be an important therapeutic target in coronary artery disease.
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PMID:Increased response to big endothelin-1 in atherosclerotic human coronary artery: functional evidence for up-regulation of endothelin-converting enzyme activity in disease. 978 93

LV systolic function and dilation after Ml have been extensively studied and have been related to heart failure and cardiac mortality. In recent years, it has been increasingly apparent that LV diastolic dysfunction contributes to signs and symptoms of heart failure and LV diastolic dysfunction is associated with increased mortality rates in patients chronic heart failure independent of systolic function. LV diastolic dysfunction is difficult to assess on basis of clinical examination including chest radiography and electrocardiography. LV diastolic filling has traditionally been evaluated by cardiac catherization with direct measurement of filling pressures and relaxation. However, the invasive approach describing LV compliance and relaxation as the major determinants of LV diastolic function, is not feasible and suitable for routine investigations of diastolic function. Two-dimensional and Doppler echocardiography has become a well accented practical and safe non-invasive method for diagnosis of LV diastolic dysfunction. Combined invasive and echocardiographic studies have shown that analysis of mitral and pulmonary venous flow velocities relate to invasively measured filling pressures and relaxation rate in cardiac diseases. Based on Doppler analysis of mitral and pulmonary venous flow three abnormal LV filling patterns are identified: impaired relaxation, "pseudonormalization" and restrictive. These LV filling patterns have been related to symptoms, relaxation rate, filling pressure and prognosis in patients with restrictive and dilated cardiomyopathy. The Doppler flow profiles are influenced by several factors including age, heart rate, load conditions and valve heart diseases which must be taken into consideration during evaluation. During the last decade information about LV diastolic function assessed non-invasively by Doppler echocardiography has gained in patients with CAD. Myocardial ischemia induced by brief coronary artery occlusion or pacing leads to abnormal myocardial relaxation which can be reversed to normal by restoring normal myocardial blood flow. The diastolic abnormality is present within seconds and a characteristic impaired relaxation filling pattern are identified by mitral and pulmonary venous flow analysis. Diastolic dysfunction has been recognized during the early as well during the post-MI phase with or without LV systolic dysfunction. In the acute phase both an abnormal relaxation pattern and restrictive LV filling pattern are present which has been related to in-hospital heart failure. The identification of a pseudonormal or restrictive LV filling pattern are associated with later readmission to hospital with heart failure and cardiac death. Abnormal relaxation filling is the most pronounced filling pattern after one year which might be related to the remodeling process including compensatory hypertrophy, scarring of the infarct zone leading to a non-uniform relaxation of the LV. Remodeling of the LV following a MI is subject to several factors which might involve diastolic function. This is supported by the presence of an impaired relaxation and restrictive filling pattern are associated with progressive LV dilatation following Ml. Furthermore, the LV remodeling process following the very early phase includes the scarring process with collagen deposition in the infarcted and non-infarcted myocardium. The extent and quality of the repair process involving collagen deposition are believed to influence the remodeling process. Increased collagen deposition in the subacute phase of Ml indicated by elevated values of the collagen marker PIIINP is found to be related to LV dilation, depressed systolic function and restrictive LV filling. Development of a restrictive filling in patients with increased collagen deposition might be due to increasing LV volume but also to increased myocardial stiffness. Regarding prognosis diastolic dysfunction seems to be an important marker of outcome as abnormal diastolic properties are related to progressive LV dilatation, development of heart failure and cardiac death following MI. The beneficial effects of BB on morbidity and mortality in post-MI patients are well established. Recently, it has been demonstrated that BB has beneficial effects on progressive CHF and cardiac mortality in patients with chronic heart failure and moderate to severe systolic dysfunction. The mechanisms behind these effects are not fully understood. However, improvement of both systolic and diastolic function during BB therapy are demonstrated in patients with CHF. A few studies in patients with MI indicates that long-term BB therapy improves LV diastolic function which seems to be followed by improvement in systolic function. BB has the potential to lengthening diastole, improving subendocardial myocardial perfusion and affecting symptomatic amd neurohumoral activation following MI which might affect LV systolic and diastolic function and thereby improving outcome. Functional capacity following Ml is a well known predictor for outcome in MI patients. LV diastolic function a closely related to exercise capacity in contrast to measures of systolic function. BB therapy in patients with mild to moderate systolic dysfunction seems to improve exercise capacity which is related to improvement in LV diastolic function. Thus, BB improves exercise capacity and diastolic function by increasing LV compliance which might have prognostic implications. Even though LV systolic and diastolic dysfunction coexist, few two-dimensional and Doppler echocardiographic variables combine measurements of both phases of the cardiac cycle. Recently, the MPI has been suggested as a measure of combined systolic and diastolic myocardial performance which is based on Doppler time intervals of the systolic and diastolic phases. The MPI is easily obtained, reproducible, non-geometric and seems less dependent on heart rate and load conditions compared to traditional Doppler measurements. In patients with MI is has shown to reflect disease severity and contain prognostic information. The assessment of MPI seems therefore to be a relevant attractive alternative to established measurements of LV function following MI.
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PMID:Clinical aspects of left ventricular diastolic function assessed by Doppler echocardiography following acute myocardial infarction. 1176 25

ICDs are the therapy of choice in patients with life-threatening ventricular arrhythmias. Mortality, morbidity, and complication rates including appropriate and inappropriate therapies are unknown when ICDs are used in routine medical care and not in well-defined patients included in multicenter trials. Therefore, the data of 3,344 patients (61.1 +/- 12.1 years; 80.2% men; CAD 64.6%, dilated cardiomyopathy 18.9%; NYHA Class I-III: 19.1%, 54.3%, 20.1%, respectively; LVEF > 0.50: 0.234, LVEF 0.30-0.50: 0.472, LVEF < 0.30: 0.293, respectively) implanted in 62 German hospitals between January 1998 and October 2000 were prospectively collected and analyzed as a part of the European Registry of Implantable Defibrillators (EURID Germany). The 1-year survival rate was 93.5%. Patients in NYHA Class III and aLVEF < 0.30 had a lower survival rate than patients in NYHA Class I and a preserved LVEF (0.852 vs 0.975,P = 0.0001). Including the 1-year follow-up, 49.5% of patients had an intervention by the ICD, 39.8% had appropriate ICD therapies, 16.2% had inappropriate therapies. Overall, 1,691 hospital readmissions were recorded. The main causes for hospital readmissions were ventricular arrhythmias (61.3%) and congestive heart failure symptoms (12.9%). Thus, demographic data and mortality of patients treated with an ICD in conditions of standard medical care seems to be comparable and based on, or congruent with, the large secondary preventions trials. When ICDs are used in standard medical care, the 1-year survival rate is high, especially in patients with NYHA Class I and preserved LVEF. However, nearly half of all patients suffer from ICD intervention.
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PMID:Mortality, morbidity, and complications in 3344 patients with implantable cardioverter defibrillators: results fron the German ICD Registry EURID. 1291 30


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