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Although the antianginal properties of molsidomine are well-established, little is known about its effects on global and regional left ventricular dysfunction secondary to myocardial ischemia. In the present study, left ventricular performance was assessed by radionuclide ventriculography at rest and during exercise in 15 patients with coronary artery disease (CAD) and angina pectoris before and after the administration of 2 mg molsidomine sublingually. Gated blood pool studies were performed for evaluation of left ventricular ejection fraction (LVEF) and regional wall motion by analyzing amplitudes and phases of the first Fourier coefficient of regional time–activity curves. In contrast to normal subjects, during the control study period LVEF in patients with CAD decreased from 50.9% at rest to 42.7% during exercise (p 0.10). In conclusion, assessment of left ventricular performance at rest and during exercise in patients with CAD revealed significant improvement of global and regional left ventricular function, indicating reduction of myocardial ischemia. These effects may result primarily from reduction of left ventricular wall tension.

The present investigation was undertaken to introduce a quantitative scintigraphic method for evaluation of regurgitation and to compare it with the generally accepted quantitative method of Sandler and Dodge (Sandler et al., 1963). Radionuclide ventriculography was carried out after injection of 20 mCi 99mtechnetium-labeled red blood cells. Time-activity curves were obtained from the left and right ventricular regions. The ratio (A) of end-diastolic-end-systolic count-rate differences for the left and right ventricles was calculated. The ratio (A) was compared with a hemodynamic ratio (Ah) determined after the method of Sandler and Dodge (1963) with the stroke volume of the left ventricle measured angiographically, and the stroke volume of the right ventricle measured by thermodilution. In 33 patients with aortic and mitral valve regurgitation we found a correlation of r = 0.75 between (A) and Ah). Due to a broad range of normal values of (A) the sensitivity of the scintigraphic method is low. The specificity seems to be high, however, since in 64 patients with all types of heart diseases there were no false positive results. Comparing the described scintigraphic method with other modern or generally accepted methods, the principal advantages are noninvasiveness, good practicability, and the fact that important additional information about the functional state of the heart is gained. This is important in follow-up studies in patients with chronic valvular incompetence. It seems that this method will become a valuable supplement to heart catheterization in the diagnosis of valvular heart disease and may partially replace invasive methods for measuring the regurgitation fraction.

The present investigation was undertaken to assess a new scintigraphic method for the diagnosis of left-to-right shunts due to atrial septal defect based on the differing stroke volumes of left and right ventricles and to compare it with oxymetric data. Radionuclide ventriculography was carried out after injection of 20 mCi /sup 99m/Tc-labeled red blood cells. Time-activity curves were obtained from the left and right ventricular regions, and the ratio (A) of end-diastolic-end-systolic count rate differences for the left and right ventricles was calculated. The left-to-right shunt (in percent of the pulmonary flow rate) is then given as 100 X (1 - A/1.43; 1.43 being the previously determined mean value of A in 66 normal patients. In 16 patients with an atrial septal defect and/or partial anomalous pulmonary venous connection a correlation of r . 0.81 was found between those shunts determined by the scintigraphic method and those calculated by oxymetric data. The specificity of the method and the sensitivity in detecting left-to-right shunts exceeding 30% are high. The method is practical and already widely used for determination of ejection fraction end-diastolic volume and other factors. The combination of this technique with other methods for shunt diagnosis such as gamma-fit analysismore » may prove of special value.« less

A new positive inotropic and vasodilator drug, AR-L 115 BS, a phenyl-imidazopyridine derivative was used for interventional ventriculography (VG) in 20 patients with coronary heart disease (CHD) and in 6 patients with dilated cardiomyopathy (CMP). Ejection fraction (EF) according to Simpsons rule was measured after biplane VG using 40–50 ml contrast medium (Urografin 76%). Ten min after IV application of 0.7 mg/kg body weight AR-L 115 BS a second VG was performed to evaluate possible improvement of wall motion. Pressures were recorded 1 and 4 min after each contrast injection and 1 and 4 min after injection of the drug. Results showed in the mean a significant increase of EF in the CHD group from 45% to 52% (P

Newly developed technologies are going to revolutionize the diagnostic procedure in cardiology. Recent progress has been made in nuclear cardiology, sonography, transmission computer tomography and digital video-techniques. Nuclear magnetic resonance seems to offer another possibility for imaging of the heart. Besides the fact, that these procedures are non-invasive and thus avoid the risks of catheter techniques, special advantages of the various techniques are obviously dependant on the cardiac abnormalities under investigation. The information revealed by these various techniques may in some ways even surpass the results obtained by catheter techniques, whereas on some occasions the catheter is obligatory. The history up to the present state of the art of the various techniques has some highlights: Nuclear cardiology started even before artificial radioisotopes were available: In 1927 BLUMGART and WEISS (1) investigated the pulmonary circulation time with the help of radon. In 1948 PRINZMETAL et al.

Die Erfassung von Parametern der globalen und regionalen Ventrikelfunktion ist erst in jungster Zeit mit nichtinvasiven Methoden moglich. Neben der zweidimensionalen Echocardiographie (Kronik et al., 1980) sind vor allem nuklear medizinische Verfahren wegen ihrer theoretischen und praktischen Vorteile von klinischem Interesse, besonders dann, wenn Informationen uber die globale und regionale linksventrikulare Funktion, wie bei der koronaren Herzkrankheit, gewonnen werden mussen.

A series of 42 patients with chest pain but normal coronary angiograms and normal haemodynamics at rest were prospectively classified as typical angina (group 1, N = 9) or atypical angina (group 2, N = 16) or non-anginal chest pain (group 3, N = 17). All patients underwent radionuclide ventriculography and measurement of pulmonary artery pressure at rest and during maximum exercise. Comparison of data during exercise revealed significantly higher (P less than 0.025) left ventricular filing pressures as reflected by the diastolic pulmonary artery pressure in group 1 (29 +/- 5 mmHg) than in both group 2 (22 +/- 6 mmHg) and group 3 (22 +/- 5 mmHg). The rest-to-exercise change in left ventricular ejection fraction was variable and not significant in group 1 (62 +/- 6% vs 63 +/- 14%). By contrast, both group 2 and group 3 had significant increases (63 +/- 6% vs 69 +/- 10%, P less than 0.02 and 63 +/- 5% vs 68 +/- 5%, P less than 0.01). The classification as 'typical angina' was predictive of an abnormal (greater than 25 mmHg) filling-pressure response to stress. The positive and negative predictive values were 78% and 70%, respectively. The clinical classification was not a predictor of an abnormal (delta less than 5%) ejection-fraction response. No correlation between radionuclide and filling-pressure data could be established. The data suggest that the majority of patients assigned to group 1 manifested an impaired left ventricular function with exercise. This was primarily related to abnormalities in diastolic filling while the systolic performance was not consistently depressed.

To determine the variation in the repeated evaluation of quantitative regional wall motion of the left ventricle (LV) from right anterior oblique (RAO) silhouettes, an intra- and inter-observer was performed in 17 patients without wall motion abnormalities, using nine different methods of regional wall motion (RWM) analysis. The results were: 1. Around the cardiac apex and near the valve plane there are regions where the subjective contour delineation yields regional mean discrepancies up to 4-5 mm (2-3 mm, respectively, near the valves); while in the other regions the mean discrepancies are usually smaller than 1 mm. 2. Absolute regional contour discrepancies, calculated in mm, show only small differences in the various methods applied for RWM analysis. 3. If these discrepancies instead are calculated as relative changes (in relative percent) of hemiaxial or segmental shortening or area diminution, the method applied is of great significance, since the length of the axes can vary considerably from method to method. 4. From all methods applied for RWM analysis, that of Mathes (radial method) had the smallest average discrepancy. These results suggest, that the LV silhouette may be best defined in the anterior and interior wall area, while in other regions subjective impressions ofmore » contour tracing may produce a considerable variation, which can be further enhanced by the method applied for RWM analysis. Methods that employ relatively large axes of as similar as possible length are therefore preferred.« less

A consecutive series of 56 patients with chest pain but no evidence of previous myocardial infarction was prospectively studied by radionuclide ventriculography to determine the value of global and regional radionuclide indices in detecting coronary artery disease. The results were correlated with the clinical judgment of chest pain, the results of the exercise electrocardiogram, and the right heart haemodynamic measurements during exercise. As a result of the criteria for entry, the study group was representative of the population seen in such a clinical setting. Only 25% of patients had coronary artery disease. The predictive power of radionuclide ventriculography was limited. The conventionally used criterion that normal subjects have an increase in left ventricular ejection fraction of at least 5% with exercise provided only 78% sensitivity and 57% specificity. Fourier analysis and visual interpretation of radionuclide studies wrongly diagnosed three out of 10 patients with extensive disease requiring surgery. These results suggest that radionuclide ventriculography is of limited value in the non-invasive diagnosis of coronary artery disease.

A series of 13 patients with significant coronary stenoses but without prior myocardial infarction were simultaneously studied by right heart catheterization and radionuclide ventriculography to determine the extent to which abnormal responses in left ventricular ejection fraction and wall motion to maximum exercise are paralleled by abnormal left ventricular filling pressures. The correlations of the filling pressure as evaluated by the diastolic pulmonary artery pressure with both the exercise ejection fraction and the rest-to-exercise change in ejection fraction were high (r = -0.89, P less than 0.01 and r = -0.76, P less than 0.01, respectively). In addition, the filling-pressure response to stress separated the patients into distinct radionuclide categories. All the 7 patients with grossly abnormal filling pressures (P greater than or equal to 30 mmHg) developed regional wall motion abnormalities with exercise as evaluated by visual interpretation or quantitative phase analysis. These patients also had a decrease in ejection fraction from rest to exercise ranging from -9% to -32% together with an exercise ejection fraction below 50%. Conversely, these abnormalities were never found in patients with filling pressures below this threshold level. The data suggest that radionuclide ventriculography and measurement of left ventricular filling pressure with exercise yield corresponding results when assessing the functional significance of coronary stenoses in normotensive patients without prior myocardial infarction and normal global left ventricular function at rest.

Fifteen consecutive patients (mean age 54 years) with proven coronary heart disease were studied with radionuclide ventriculography. After resting and exercise control studies, repeat studies were performed after administration of 4 mg of molsidomine sublingually and again after administration of 10 mg of metoprolol intravenously. Rest to exercise ejection fraction (EF) decreased significantly. This was significantly attenuated by molsidomine and by metoprolol. In a subset of nine patients with exercise ischemia, EF showed significant (p less than 0.05) improvement after molsidomine administration (46.7 +/- 13.7% to 57.1 +/- 16.7%), which was diminished to 54.4 +/- 10.5% after metoprolol administration. In the subgroup without exercise ischemia, molsidomine increased the EF to a lesser extent (47.3 +/- 12.7% to 52.6 +/- 13.4%, p less than 0.05). After administration of metoprolol the EF decreased below the control level (44.4 +/- 10.6%). Regional Fourier amplitudes accentuated the differences between the two groups. We conclude that molsidomine and metoprolol improve left ventricular function in patients with coronary heart disease and ischemia during exercise. In patients with reduced left ventricular function without signs of ischemia, molsidomine improves function as well and should be used additionally, if beta blockers are indicated for other reasons.

In vorausgegangenen Untersuchungen von Hein, Fleckenstein, Janke, Eckardt und Ludin (1972) wurde daruber berichtet, das es bei der experi­mentellen Linksherz-Hypertrophie der Ratte nach Coarctation der Aorta zu einer auffalligen Einschrankung der β-adrenergen Myokardreaktionen kommt Die physiologische Grundwirkung β-adrenerger Catecholamine -­insbesondere von Isoproterenol — besteht bekanntlich am Ventrikelmyokard in einer Erhohung des transmembranaren Ca++-Einstroms. Hierdurch wird die Ca++-abhangige Myofibrillen-ATPase starker aktiviert und die ATP-Spaltung im kontraktilen System gesteigert. Hieraus resultiert dann die bekannte positiv inotrope Catecholamin-Wirkung. Am hypertrophierten Rattenherzen waren dagegen alle diese β-adrenergen Effekte stark abge­schwacht. So konnte gezeigt werden, das die Radiokalzium-Nettoaufnahme in normale Kontroll-Herzen durch 1 mg Isoproterenol/kg um den Faktor 4 gesteigert werden kann. Injiziert man jedoch die gleiche Isoproterenol-Dosis den Tieren 3 Wochen nach der Aortenkonstriktion, so wird der Radiokalzium-Einbau in das hypertrophierte linke Ventrikelmyokard nur noch geringfugig erhoht. Dabei schien die Einschrankung der β-adrenergen Sti mulierbarkeit mit der Entwicklung des Hypertrophie-Grades quantitativ korreliert zu sein. Je groser das Herz, desto geringer war die mit Radiokalzium quantifizierte β-adrenerge Reaktivitat.

Background Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events. We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure. Methods We recruited patients from October, 1997, to June, 2000. 13655 patients were registered with previous myocardial infarction (64%), angiographic evidence of coronary artery disease (61%), coronary revascularisation (55%), or a positive stress test only (5%). After a run-in period of 4 weeks, in which all patients received perindopril, 12218 patients were randomly assigned perindopril 8 mg once daily (n=6110), or matching placebo (n=6108). The mean follow-up was 4.2 years, and the primary endpoint was cardiovascular death, myocardial infarction, or cardiac arrest. Analysis was by intention to treat. Findings Mean age of patients was 60 years (SD 9), 85% were male, 92% were taking platelet inhibitors, 62% beta blockers, and 58% lipid-lowering therapy. 603 (10%) placebo and 488 (8%) perindopril patients experienced the primary endpoint, which yields a 20% relative risk reduction (95% CI 9-29, p=0.0003) with perindopril. These benefits were consistent in all predefined subgroups and secondary endpoints. Perindopril was well tolerated. Interpretation Among patients with stable coronary heart disease without apparent heart failure, perindopril can significantly improve outcome. About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event. Treatment with perindopril, on top of other preventive medications, should be considered in all patients with coronary heart disease.

Radionuclide ventriculography (RNV) is now a well-established procedure for the noninvasive evaluation of cardiac hemodynamics, including the detection and quantification of valvular regurgitation. 46 patients undergoing aortic or mitral valve replacement were examined by RNV pre- and postoperatively. The specificity of RNV in the diagnosis of aortic or mitral incompetence was high. All cases of moderate to severe aortic regurgitation were identified. This, however, was not true for mitral incompetence. A significant overlap between the left atrium and the left ventricle in the LAO view is held responsible for this decrease in sensitivity. The quantification of aortic regurgitation and the assessment of left ventricular function by RNV appears to hold promise in the preoperative workup. This diagnostic approach yields important additional information, which may be essential in the appropriate timing of surgical intervention. Aortic valve replacement for incompetence as well as for stenosis was accompanied by a significant improvement in global left ventricular ejection fraction. No postoperative change in ejection fraction was found in cases of mitral incompetence, while a slight increase was observed following operative therapy for mitral stenosis. The radioisotope findings were correlated to the results obtained by cardiac catheterization and noninvasive techniques such as echocardiography. The place of RNV in the pre- and postoperative management of valvular heart disease is delineated in this paper. It is of special value in the evaluation of aortic incompetence and may be an important diagnostic adjunct in the approach to the patient with mitral valve disease or aortic stenosis.

This review focuses on the impact of nickel on human health. In particular, the dual nature of nickel as an essential as well as toxic element in nature is described, and the main forms of nickel that can come in contact with living systems from natural sources and anthropogenic activities is discussed. Concomitantly, the main routes of nickel uptake and transport in humans are covered, and the potential dangers that nickel exposure can represent for health are described. In particular, the insurgence of nickel-derived allergies, nickel-induced carcinogenesis as well as infectious diseases caused by human pathogens that rely on nickel-based enzymes to colonize the host are reviewed at different levels, from their macroscopic aspects on human health to the molecular mechanisms underlying these points. Finally, the importance of nickel as a beneficial element for human health, especially being essential for microorganisms that colonize the human guts, is examined.

The dramatic changes in the environmental conditions that organisms encountered during evolution and adaptation to life in specific niches, have influenced intracellular and extracellular metal ion contents and, as a consequence, the cellular ability to sense and utilize different metal ions. This metal-driven differentiation is reflected in the specific panels of metal-responsive transcriptional regulators found in different organisms, which finely tune the intracellular metal ion content and all metal-dependent processes. In order to understand the processes underlying this complex metal homeostasis network, the study of the molecular processes that determine the protein-metal ion recognition, as well as how this event is transduced into a transcriptional output, is necessary. This chapter describes how metal ion binding to specific proteins influences protein interaction with DNA and how this event can influence the fate of genetic expression, leading to specific transcriptional outputs. The features of representative metal-responsive transcriptional regulators, as well as the molecular basis of metal-protein and protein-DNA interactions, are discussed on the basis of the structural information available. An overview of the recent advances in the understanding of how these proteins choose specific metal ions among the intracellular metal ion pool, as well as how they allosterically respond to their effector binding, is given.

56 pages; International audience

Urease is the enzyme that catalyzes the hydrolysis of urea as the last step of organic nitrogen mineralization in the environmental nitrogen cycle. The two Ni(II) ions present in the active site are essential for this enzymatic reaction. This review describes and critically discusses the major advances in the understanding of the chemistry of the metal ions that have been achieved in the past 10 years, mainly through the application of high resolution X-ray crystallography. In particular, the structure of the enzyme in its native form is described, as well as the structure of the enzyme complexed with small un-reactive molecules mimicking the structure of the substrate and the transition state of the reaction, thus providing snapshots of the reaction mechanism. In addition, the discussion of the structures of urease complexed with competitive inhibitors provides further insights into the reactivity of the nickel ions in the active site. Overall, this information is used to discuss the chemical role of the nickel ions for this hydrolytic reaction, fundamental both in medicine as well as in agriculture.