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Biomedical subjects

T Stefenelli

Publications and source records attributed to T Stefenelli.

At least 37 records · Page 2Linked to original sources

Urinary excretion of apo(a) fragments. Role in apo(a) catabolism.

The biosynthesis and assembly of lipoprotein(a) [Lp(a)], a marker for atherosclerotic disease, appears to be well understood. However, information is lacking concerning the mode and site of Lp(a) catabolism. Apo(a) is reported to be excreted into the urine. To study the effect of this pathway on the overall catabolism of Lp(a), urinary apo(a) was characterized by immunoblotting. More than 10 distinct apo(a) bands with molecular masses between 30 and 160 kD were observed. Apo(a) fragments were not complexed to apoB. In more than 30 individuals the size of apo(a) bands was comparable irrespective of their apo(a) phenotype, although marked differences in the relative intensities of the bands were observed. Eight batches of 24-hour urine collections collected from one proband at 2-week intervals exhibited a significant correlation between creatinine and apo(a) concentrations as measured by DELFIA (r = .93; P < .01). In 193 healthy volunteers a highly significant correlation was found between urinary apo(a) concentrations normalized to creatinine levels and plasma Lp(a) values (p = 0.659; P < .0001). Of the total plasma apo(a), 0.073%, i.e., 121 micrograms apo(a), was excreted in the form of apo(a) fragments in 24-hour urine samples from 12 healthy volunteers. We conclude that the catabolism of Lp(a) via excretion of apo(a) fragments accounts for < 1% of the daily Lp(a) catabolism.

Adult↗

Implantable cardioverter-defibrillator dysfunction after coronary artery bypass grafting.

Displacement of an ICD electrode is a possible complication after changes in heart size after CABG and simultaneous implantation of an epicardial lead ICD. To prevent potentially life-threatening ICD dysfunction in patients who are candidates for CABG and ICD implantation, we suggest the use of transvenous ICD systems or a staged procedure (CABG followed by ICD implantation) rather than a simultaneous operation.

Coronary Artery Bypass↗

Primary hyperparathyroidism: incidence of cardiac abnormalities and partial reversibility after successful parathyroidectomy.

PURPOSE: This prospective study was designed to assess the effect of primary hyperparathyroidism on heart muscle, valves, and myocardial function. Echocardiography was used to evaluate changes in mechanical performance, the thickness of the left ventricular wall, myocardial calcific deposits, and valvular calcifications in patients with primary hyperparathyroidism. METHODS: Echocardiography was performed in 54 patients with hyperparathyroidism prior to surgery and 12 +/- 2 months after successful parathyroidectomy. A matched control group was followed for comparison. RESULTS: In a blinded fashion, aortic and mitral valve calcifications were detected in 63% and 49% of patients with primary hyperparathyroidism (controls: 12% and 15%, respectively). Calcific deposits in the myocardium were found in 69% of patients with hyperparathyroidism and 17% of the control subjects. After parathyroidectomy and 12 months of normocalcemia, a significant regression of left ventricular hypertrophy (p < 0.001) was observed. CONCLUSIONS: The present data show a high incidence of left ventricular hypertrophy, calcific deposits in the myocardium, and/or aortic and mitral valve calcification in patients with primary hyperparathyroidism. A 1-year follow-up after parathyroidectomy (and restoration of normocalcemia) discloses regression of hypertrophy, while calcifications persist without evidence of progression.

Adult↗

[Cardiac changes in patients with hypercalcemia].

Patients with hypercalcaemia have a markedly greater risk of dying from cardiovascular disease than normocalcaemic age- and sex-matched controls. Cardiovascular findings in hypercalcaemic patients frequently include characteristic ECG changes, left ventricular hypertrophy, and myocardial calcific deposits. Furthermore, these subjects have a higher incidence of angina pectoris and calcification of the heart valves. Baseline screening for hypercalcaemia should include ECG and echocardiography.

Angina Pectoris↗

Intracellular calcium during pacing-induced ventricular fibrillation. Effects of lidocaine.

Hemodynamics and endocardial [Ca2+]i transients were studied during ventricular fibrillation in isolated perfused rat hearts. During 1 minute of pacing-induced ventricular fibrillation, the diastolic fibrillatory [Ca2+]i level increased significantly (p less than 0.001) above the end-systolic [Ca2+]i concentration of the last regular contraction. A bolus of lidocaine led to a decrease in the [Ca2+]i level during fibrillation (p less than 0.007) to the end-diastolic level of baseline conditions and then subsequently converted the heart to sinus rhythm. In 13 (62%) of the 21 studies described, post-lidocaine ventricular fibrillation converted to a brief period of asystole followed by sinus rhythm; in 8 (38%) of the studies, post-lidocaine ventricular fibrillation switched to ventricular tachycardia. Postfibrillatory cardiac dysfunction was related to the duration and degree of elevated diastolic [Ca2+]i. The authors conclude that [Ca2+]i levels are increased during ventricular fibrillation, and that lidocaine treatment leads to a prompt decrease in [Ca2+]i preceding conversion to sinus rhythm.

Animals↗

Effects of propafenone on pacing-induced ventricular fibrillation and intracellular calcium in rat hearts.

Propafenone is an antiarrhythmic agent with fast sodium channel, calcium channel, and beta-adrenergic receptor blocking properties. The effects of propafenone on arrhythmias, free intracellular calcium and left ventricular performance were studied using perfused rat hearts during (i) pacing-induced ventricular fibrillation and (ii) infusion with 2.65 x 10(-6) M, 5.3 x 10(-6) M and 7.9 x 10(-6) M propafenone hydrochloride (corresponding to approximately 1, 2 and 3 mg kg-1 body weight). A bolus of 1 mg kg-1 propafenone during ventricular fibrillation resulted in a decrease in intracellular calcium, with subsequent conversion to sinus rhythm. In perfused hearts with sinus rhythm propafenone produced a dose-dependent decrease in heart rate and myocardial oxygen consumption together with a rise in left ventricular diastolic pressure, and diastolic [Ca2+]i, indicative of depression of left ventricular function. We conclude that a bolus of propafenone during ventricular fibrillation leads to a decrease in [Ca2+]i preceding conversion to sinus rhythm. In rat hearts with sinus rhythm the depressive effects of propafenone on [Ca2+]i are dose dependent.

Animals↗

Heart rate behaviour at different stages of congestive heart failure.

Depressed heart rate variation has been shown to predict a high mortality rate in patients with severe congestive heart failure. To determine whether the degree of altered heart rate correlates with the clinical state, 24-h Holter monitoring was performed in 21 patients (mean ejection fraction: 18 +/- 11%) at baseline and after 6 months of oral therapy. At baseline, the overall 24-h heart rate variation and night/day heart rate ratio was reduced, depending on the NYHA functional class. The typical morphology of R-R interval histograms was a sensitive marker of the clinical state at baseline: the higher the NYHA class, the smaller the R-R interval variability and standard deviation of R-R intervals (total variability NYHA III versus II: P less than 0.05). Clinical deterioration after 6 months (n = 8) was accompanied by a tendency to further shortening of the mean total R-R interval variability (676 +/- 34 to 586 +/- 25 ms). This was shown in three patients, who were reclassified to NYHA class IV. In stable patients (n = 5) and those with clinical improvement (n = 8) no significant change in R-R variability was observed. It is concluded that variations in R-R interval histogram shapes correspond to different NYHA functional classes. While severe clinical disease progression may be associated with further reductions in the heart rate variability, improvement in the clinical state of congestive heart failure is not necessarily associated with changes in heart rate behaviour.

Adult↗

[Importance of intracellular calcium homeostasis for contraction and relaxation of the heart muscle].

The method of surface fluorometry with indo-1 allows the simultaneous quantitative recording of changes in free intracellular calcium ([Ca2+]i) transients during the cardiac cycle and haemodynamic parameters and ECG. Using this method, recent studies gave further insight into acute and chronic changes in [Ca2+]i during disease (e.g. heart failure, ischaemia, arrhythmias), as well as pharmacologic interventions. The failing myocyte is characterized by small calcium transients and elevated end-diastolic [Ca2+]i concentrations. Without an adequate delivery of substrate to the mitochondria (pyruvate, but not glucose) the cardiomyopathic heart muscle is no longer capable of maintaining its [Ca2+]i homeostasis. In healthy hearts, positive inotropic agents lead to an increase in developed pressure commensurately with the percentage changes in amplitude of the [Ca2+]i transients, while the end-diastolic [Ca2+]i levels seem to depend on the activation of cAMP. In failing hearts the latter finding may explain the different behaviour of end-diastolic [Ca2+]i and haemodynamics during perfusion with various catecholamines, more likely stimulating alpha- and/or beta-adrenoceptors. Further studies analysed [Ca2+]i during ischaemia or showed the importance of changes of [Ca2+]i in the genesis of premature beats and the initiation of tachyarrhythmias, in particular ventricular fibrillation. The present overview underlines the comprehensive role of calcium homeostasis in the pathophysiology of contraction and relaxation of the heart muscle.

Animals↗

[Pimobendan (UDCG 115 BS) in long-term therapy of chronic heart failure].

Pimobendan is a positive inotropic agent with additional calcium-sensitizing effects of the phosphodiesterase III-inhibitor group. In short-term studies, beneficial hemodynamic effects have been demonstrated in patients with congestive heart failure. The aim of this prospective study was to examine the long-term effect of pimobendan (during at least 6 months) on subjective state, hemodynamic parameters, and arrhythmias in patients with congestive heart failure NYHA classes II and III. After double-blind randomization, 24 patients received pimobendan 5 mg bid or placebo orally in addition to a basic therapy (diuretics, digitalis). After 3 months, pimobendan-treated patients showed a significant clinical improvement (p < 0.03). In the placebo group, one patient underwent acute cardiac transplantation due to rapid clinical deterioration; another patient died suddenly after 5 months. No cardiac events occurred in the pimobendan group. In comparison to placebo, no proarrhythmogenic effect of pimobendan was detected. Clinical stabilization of patients in the pimobendan group was not paralleled by improvement of the hemodynamic parameters of left-ventricular performance.

Cardiac Volume↗

Parathyroid hormone and calcium behavior in advanced congestive heart failure.

Parathyroid hormone (PTH) regulates the content of calcium and thus exerts an effect on myocardial function. Abnormal secretion of PTH has been sporadically reported to be associated with depressed mechanical performance of the heart muscle. In the present study, we first measured PTH levels at baseline in 27 consecutive patients with advanced congestive heart failure (LVEF: 17 +/- 9%): five patients (18.5%) revealed elevated PTH levels, one case of hypoparathyroidism was discovered. Furthermore, nine unselected patients underwent symptom-limited exercise stress test leading to an increase in mean pulmonary artery pressure from 25.6 +/- 15 at baseline to 41.2 +/- 18 mm Hg at peak exercise. In contrast to observations in healthy subjects, in heart failure patients both mean PTH and blood calcium concentrations did not change significantly during peak exercise or recovery. Moreover, patients with the lowest left-ventricular ejection fraction showed a decrease in PTH during maximal stress. We conclude that abnormal baseline PTH secretion is common in patients with advanced congestive heart failure. More importantly, these studies show that PTH release is depressed under stress conditions, possibly indicating a dysfunction of the parathyroid gland in severe heart failure.

Adult↗

[Ca2+]i transients in the cardiomyopathic hamster heart.

Intracellular [Ca2+] transients were studied in isolated hearts of healthy and cardiomyopathic hamsters in late failure perfused with glucose or pyruvate. Hearts of healthy hamsters developed similar pressures when perfused with either glucose or pyruvate, and [Ca2+]i transients were comparable in amplitude when perfused with either substrate. On the other hand, hearts of cardiomyopathic hamsters in late failure developed normal pressure when perfused with pyruvate but developed depressed pressure (50%) when perfused with glucose. The amplitude of [Ca2+]i transients fell severely and was associated with a high diastolic [Ca2+]i in cardiomyopathic hamster hearts when the perfusate was switched from pyruvate to glucose. The high phosphomonoester sugars as evidenced by 31P nuclear magnetic resonance studies and the depressed oxygen consumption in the cardiomyopathic hamster hearts perfused with glucose reflect an inhibition in glycolysis and a subsequent decrease in mitochondrial activity. Without an adequate delivery of substrate to the mitochondria in the cardiomyopathic hamster, the myocardium is no longer capable of maintaining its [Ca2+]i homeostasis.

Animals↗

[Positive inotropic substances in therapy of heart failure: digitalis, catecholamines, phosphodiesterase inhibitors].

The discussion about the importance of inotropic agents in the treatment of congestive heart failure is still open. A review of studies concerning the effects of digitalis, adrenoceptor stimulating or blocking agents, as well as phosphodiesterase inhibitors on hemodynamics and the physical state of heart failure patients is presented. Most authors agree that digitalis is indicated in patients with impaired left ventricular function and supraventricular arrhythmias, as well as in patients with heart failure who remain symptomatic during treatment with diuretics and vasodilators. While adrenoceptor stimulation with catecholamines is widely accepted in patients with acute and severe heart failure, beta-receptor blockers seem to have beneficial effects on some patients with mild to moderate congestive heart failure.

Cardiotonic Agents↗

Transient myocardial perfusion abnormalities during cold provocation test in patients with arterial hyperreactivity.

The effect of peripheral cold provocation on myocardial perfusion was evaluated utilizing thallium-201 perfusion imaging in 13 selected patients with arterial hyperreactivity (Raynaud's phenomenon: n = 8; migraine: n = 6) and angiographically documented coronary artery spasm. Eleven out of 13 subjects with coronary arterial spasm--but none of a group of patients with obstructive coronary artery disease--had transient myocardial perfusion defects during cold provocation. The localization of transient perfusion abnormalities during myocardial scintigraphy correlated with the myocardial areas distal to the spontaneous or ergonovine-induced coronary arterial spasm detected by angiography. Transient reduction of tracer uptake during cold provocation and normalization of myocardial perfusion by redistribution imaging was paralleled by areas of hypokinesia observed during the test by contrast ventriculography (n = 8). The described findings in the coronary system during peripheral cold pressor test occurred independently of the presence of Raynaud's phenomenon, and without achieving the ischemic threshold.

Adult↗

[Myelosarcoma of the ovary].

The case is reported of a patient with granulocytic sarcoma of the right ovary and infiltration of granulocytic precursor cells into abdominal lymph nodes without any evidence of acute leukaemia on examination of the blood and bone marrow. Removal of the tumour and subsequent polychemotherapy was followed by remission. A local recurrence was treated with radiation and high-dose polychemotherapy. The patient has now been in complete remission for seven years. Thus, granulocytic sarcoma may have a good prognosis if treated with aggressive therapy, including operation, radiation, and high-dosage polychemotherapy.

Adult↗

Digital vascular reactivity in patients on haemodialysis treated with human recombinant erythropoietin.

Digital vascular reactivity was determined in 12 normotensive patients on chronic hemodialysis without a history of Raynaud's phenomenon before and after partial correction of anaemia with human recombinant erythropoietin (rHuEPO): apparent finger systolic pressures and finger skin temperatures were recorded at rest, after local cooling, and following 5 minutes rewarming time. Finger systolic pressures remained constant during the whole test, pre and post rHuEPO therapy. The decrease in finger skin temperatures after cold provocation as well as the rewarming behaviour after cooling were normal in both examinations. The present data indicate that treatment with EPO does not interfere with digital arterial reactivity in normotensive patients on haemodialysis.

Adult↗

Plasminogen activator inhibitor-1 levels in patients with chronic angina pectoris with or without angiographic evidence of coronary sclerosis.

Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to exist in 40 to 60% of patients with stable coronary artery disease and have been suggested to be responsible for the development of coronary thrombotic complications. However, it is also discussed whether PAI-1 elevation might mainly be due to variables like increased age or to reactive mechanisms caused e.g. by the chest pain itself. To exclude age dependent or pain related influences, age-matched patients with stable angina pectoris (NHYA II) and angiographically proven coronary artery disease (CAD, n = 16) or without evidence for coronary sclerosis (variant angina, n = 10; angina-like syndrome with normal coronary angiogram, n = 5; non-CAD, n = 15) have been investigated for their plasma PAI-1 activity and t-PA antigen levels. The mean PAI activity in CAD patients (17.5 U/ml) was significantly higher than in non-CAD patients (9.6 U/ml) (p less than 0.0001). In the CAD patients no significant variation in plasma PAI-1 values could be demonstrated when related to the extent of the disease or to a history of previous myocardial infarction. t-PA antigen was also elevated in CAD patients as compared to the non-CAD group (p less than 0.02). The results suggest therefore a strong correlation between coronary artery disease itself and elevated levels of components of the plasma fibrinolytic system.

Angina Pectoris↗

[Heart transplantation: indication, selection criteria and patient management].

Evaluation of potential candidates for cardiac transplantation is a difficult and wearisome process for both physician and patients. As long as we are confronted with the present situation of an increasing chronic donor unavailability, the importance of standardized, rational criteria for evaluation of heart transplantation candidates has to be emphasized, since the success of any organ transplantation depends on adequate selection of potential candidates.

Biopsy, Needle↗