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Biomedical subjects

M Sigmund

Publications and source records attributed to M Sigmund.

At least 19 recordsLinked to original sources
PubMed1995

Hypertrophic cardiomyopathy: a desensitized cardiac beta-adrenergic system in the presence of normal plasma catecholamine concentrations.

Only few data are available concerning the biochemical and functional state of the beta-adrenergic system in hypertrophied human myocardium. The present study was to investigate the myocardial beta-adrenergic signal transduction system in hypertrophic obstructive cardiomyopathy (HOCM). Thin myocardial strips were prepared from surgically excised, septal myocardium from 7 patients with HOCM and their force of contraction was measured in vitro. The positive inotropic effects of calcium and dihydro-ouabain, both acting independently of beta-adrenoceptors and cAMP, were similar in these preparations to those, previously published, seen with nonfailing myocardium. In contrast, the beta-adrenoceptor agonist isoprenaline and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) had reduced positive inotropic effects. Their EC50-values were about 10 fold higher than the respective EC50-values published for nonfailing myocardium. The positive inotropic potencies of isoprenaline and IBMX were reduced in HOCM by as much as they were in the additionally investigated myocardium from 6 patients with severe mitral regurgitation (MR, NYHA III). In order to clarify whether the functional alterations are related to changes in the beta-adrenoceptors, beta-adrenoceptor density and beta 1: beta 2-adrenoceptor subtype distribution were determined in the same myocardium using 125I-Iodocyanopindolol saturation binding. Myocardial beta-adrenoceptor density was reduced to 68% in HOCM and to 56% in MR compared to nonfailing myocardium controls (NF: 64.8 +/- 6.5 fmol/mg protein). In HOCM, this reduction was due to a selective down regulation of beta 1-adrenoceptors (24.9 +/- 3.7 fmol/mg protein vs NF: 46.4 +/- 6.8 fmol/mg protein, P < 0.05), whereas beta 2-adrenoceptor density was unchanged (19.0 +/- 1.9 fmol/mg protein vs NF: 18.4 +/- 3.3 fmol/mg protein, n.s.). In MR both beta-adrenoceptor subtypes were reduced (beta 1: 26.9 +/- 1.4 fmol/mg protein, beta 2: 9.6 +/- 1.7 fmol/mg protein; both P < 0.05 vs NF). Electrochemically determined plasma catecholamine levels were elevated in MR. However, plasma catecholamine levels were normal or slightly below normal in HOCM. In summary, myocardial beta-adrenoceptors are downregulated and their function is impaired in HOCM. This desensitization is not caused by a negative feedback regulation due to increased plasma catecholamines. The present results show that the desensitizations of the beta-adrenergic system associated with HOCM has characteristics that indicate a major deviation in its development from that of the beta-adrenergic desensitization previously described to occur in congestive heart failure.

Adult↗
PubMed1995

Effect of captopril on myocardial beta-adrenoceptor density and Gi alpha-proteins in patients with mild to moderate heart failure due to dilated cardiomyopathy.

In end-stage heart failure due to idiopathic dilated cardiomyopathy beta 1-adrenoceptors are downregulated and Gi alpha-proteins are upregulated. The aim of the present study was to investigate the influence of the angiotensin-converting enzyme inhibitor captopril on beta-adrenoceptor density and Gi alpha-proteins in sequential endomyocardial biopsies. Nineteen patients with mild to moderate congestive heart failure due to idiopathic dilated cardiomyopathy (NYHA Class II-III) were studied before and after 8-11 weeks of therapy. Patients were randomised into a captopril and a control group; 9 patients received captopril 12.5-50 mg per day, (divided in 2-3 doses) p.o. in addition to "conventional" therapy with digoxin and diuretics, and 10 controls received "conventional" therapy only. Echocardiography, spiroergometry, right heart catheterisation and endomyocardial biopsies were performed before (baseline) and after treatment. Compared to baseline, captopril increased total beta-adrenoceptor density by selectively increasing beta 1-adrenoceptors (31.6 vs 41.2 fmol.mg-1; p < 0.05) but had no significant effect on Gi alpha-proteins. The results indicate that treatment with angiotensin-converting enzyme inhibitors partly restores myocardial beta 1-adrenoceptor density, and this action effect may contribute to the clinical improvement of patients with idiopathic dilated cardiomyopathy treated in this way.

Adenosine Diphosphate Ribose↗
PubMed1995

[Beta receptor blockers in chronic heart failure].

Recently published data of the controlled MDC- and CIBIS-trials confirm the favorable effect of beta-blocker therapy on the hemodynamics and clinical course of patients with chronic heart failure due to dilatated and/or ischemic cardiomyopathy. However, mortality remains unchanged. The mechanisms by which beta-blocker therapy improves hemodynamics in chronic heart failure are not known reliably. It is postulated that the negative chronotropic effect of beta-blockers improves the cellular calcium metabolism and thereby increases myocardial contractility. Further effects of beta-blockers are protection of myocardial cells from enhanced catecholamine concentrations. This prevents cell necrosis and economizes the use of cell energy. The reversion of down-regulation of beta-1-receptors in beta-blocker therapy is most probably only an epiphenomenon. Major randomized clinical trials are ongoing to investigate whether improved hemodynamics and clinical course are correlated with decreased mortality. It also still remains open which substance is most beneficial (e.g., selective beta-blockers, beta-blockers with additional vasodilatatory effect).

Adrenergic beta-Antagonists↗
PubMed1995

[Chronic frequency-adaptive pacemaker therapy in patients with heart failure].

Twenty patients (complete AV block n = 13, sick sinus syndrome n = 4 (replacement of a VVI system), bradyarrhythmia n = 3) with rate-adaptive pacemakers (respiration volume guided n = 10, QT-driven n = 1, dual sensor (QT/activity) system n = 9) were randomly assessed by ergospirometry after 4 weeks of VVI- (70 bpm), VVIR1-(70-110 bpm, low upper rate) and VVIR2-pacing (70-130 bpm, high upper rate). Oxygen uptake (VO2), work load (W), and heart rate were determined at peak exercise (max) and at the anaerobic threshold (AT). In the whole population, rate adaptation led to a significantly higher VO2-max than VVI-pacing for both VVIR1- (15.5 +/- 5.1/12.6 +/- 4.1 ml/kg/min, 28 +/- 37%, p < 0.01) and VVIR2-pacing (14.8 +/- 4.4/12.6 +/- 4.1 ml/kg/min, 20 +/- 23%, p < 0.01). At the AT, however, VO2 was significantly improved only by the VVIR1 mode (low upper rate, 9.8 +/- 2.5/8.0 +/- 2.1 ml/kg/min, 28 +/- 36%, p < 0.01). Regarding only patients with moderately limited exercise capacities (Weber class C, n = 11), rate adaptive VVIR1 and VVIR2 pacing could not produce a significant increase of VO2-max and VO2-AT. In contrast, patients with severely reduced exercise capacities (Weber class D, n = 9) significantly profited from the rate adaptation, but only in the VVIR1 mode (VO2-max 48 +/- 45%, VO2-AT 51 +/- 38%, p < 0.01). Thus, in the whole population an increase of oxygen uptake and of exercise workload at the anaerobic threshold could only be achieved by pacing with the low upper rate of 110 bpm. By this, particularly patients with heart failure and a severely limited exercise tolerance (Weber D) had a significant benefit. Therefore, the upper rate should be programmed in a lower range in patients with heart failure, at least for rate-adaptive ventricular pacemaker systems.

Aged↗
PubMed1994

Dynamic training of skeletal muscle ventricles. A method to increase muscular power for cardiac assistance.

BACKGROUND: Skeletal muscle can be used for cardiac assistance after electrical stimulation over a period of several weeks. This will adapt it to do chronic work with no resulting fatigue. The result of this procedure, however, is a reduction of 80% in muscle power, > 60% in muscle mass, and approximately 85% in contractile speed. To minimize these disadvantages, the following study was done to develop and test a method to dynamically train skeletal muscle ventricles (SMVs). METHODS AND RESULTS: Barrel-shaped SMVs were tested in 15 Jersey calves. They were made from the latissimus dorsi muscle, which was wrapped around an elastic silicone training device. Six SMVs were used extrathoracically in a single layer and nine intrathoracically in a double layer. With dynamic training preserving contractile speed, the output increased to approximately 5 L/min, the systolic pressure increased to > 200 mm Hg, and power developed to approximately 10 W after 3 months of dynamic training. The contractile speed of dynamically trained SMVs was between 250 and 700 mm/s. The diameter of the latissimus dorsi muscle increased to three times that of the corresponding contralateral muscle. CONCLUSIONS: The combination of electrical conditioning with dynamic training of the SMVs resulted in a strong muscle pump that did not develop fatigue. Dynamic training for skeletal muscle represents a new and promising method for providing powerful autologous cardiac assist.

Animals↗
PubMed1994

A comparative study of the concentrations of hypoxanthine, xanthine, uric acid and allantoin in the peripheral blood of normals and patients with acute myocardial infarction and other ischaemic diseases.

The aim of this study was the elucidation of the role of the xanthine oxidoreductase in the purine metabolism in ischaemic diseases of man. The serum concentrations of hypoxanthine, xanthine, uric acid and allantoin were determined in peripheral blood samples from patients with angina pectoris, cerebral insult and myocardial infarction with thrombolytic therapy and were compared with the concentrations obtained for healthy males and females. No significant differences were observed for the serum hypoxanthine concentrations, xanthine concentrations, the sum (hypoxanthine+xanthine) and the ratio (xanthine/hypoxanthine) between the healthy males, healthy females, the patients suffering from angina pectoris and the patients suffering from cerebral insult. An increase of the serum xanthine concentration in patients with myocardial infarction indicates a significant metabolic involvement of xanthine oxidoreductase in this disease and therefore a possible role in the development of tissue damage in the postischaemic phase due to oxygen radicals generated by the oxidase activity of this enzyme. The serum concentrations of uric acid and allantoin showed no differences between any of the studied groups. Study of the non-enzymatic oxidation of uric acid to allantoin by oxygen radicals, a relevant radical-scavenging mechanism in other diseases, provided no indication of an increased concentration of oxygen radicals due to the xanthine oxidoreductase reaction or other radical-producing mechanisms.

Adult↗
PubMed1994

[Ergospirometric findings in respiration- and QT-controlled pacemakers].

This study used ergospirometry with quantification of gas exchange parameters to analyze the beneficial effects of two sensors for rate responsive pacing: QT-interval and minute ventilation (MV). Bicycle exercise testing was performed with modulating VVIR pacing modes in random sequence. Rate responsiveness effected a mean increase of exercise tolerance of 31.1% in the QT group and 22.6% in the MV group. With both systems maximal oxygen uptake increased by 29.4% (QT) and 28.3% (MV). Oxygen consumption at the anaerobic threshold was improved by 28.3% (QT) and 32.1% (MV). The increase of cardiopulmonary parameters achieved by rate responsiveness was significant (p < 0.05) without significant difference in comparison between both groups. Despite the initially delayed rate increase at the onset of exercise mediated by the QT-interval, the programmed upper rate limit was satisfactorily attained by both principles. Thus, both sensors--minute ventilation and QT-interval--provide an adequate rate modulation in response to exercise and a marked improvement of cardiopulmonary work capacity.

Anaerobic Threshold↗
PubMed1994

[Cardiopulmonary exercise capacity before and after heart transplantation].

The aim of heart transplantation is to improve survival and exercise capacity of patients with endstage heart failure. Fifteen patients (1 female, 14 male) with a mean age of 48 years (ranging from 25-62) underwent cardiopulmonary exercise testing (CPX) before heart transplantation. 10/15 patients showed an oxygen uptake of < 4 ml/min/kg (Weber E) at the anaerobic threshold and 5/15 an oxygen uptake between 5 and 8 ml/min/kg (Weber D), so that a severe respectively very severe limitation of exercise capacity was documented before transplantation. Up to now 9/15 patients underwent heart transplantation. Cardiopulmonary exercise test could be repeated in 7 of these 9 patients, 12 up to 22 weeks following operation. Exercise capacity improved from former Weber-class E to class B in 2/5 patients, to class C in 2/5 patients, and to class D in 1/5 patient. Both patients with a preoperative class D improved to class C. Thus, in all cardiac recipients exercise capacity increased, whereas normal values were not reached. The denervation of cardiac allografts leads to a higher heart rate at rest, a delayed increase and diminished slope of exercise response and reduced heart rates at maximal effort. In 17 heart transplant recipients (3 female, 14 male) with a mean age of 53 years (ranging from 25-62), we investigated the exercise capacity with respect to the abnormal rate regulation of the donor heart, which was quantified by comparing the corresponding rate regulation of the remaining part of recipient's atrium driven by the sinus mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[An increase in cardiopulmonary exercise tolerance after the embolization of a pulmonary arteriovenous fistula].

A 21-year-old woman suffering from increasing dyspnoea on intense physical exercise, was found to have a congenital right-sided arteriovenous pulmonary fistula. This was successfully and without complication embolized using a percutaneously introduced Gianturco wire coil. All symptoms disappeared after this procedure. Definite improvement in physical performance, in comparison with pre-embolization values, was documented by spiroergometry as early as two days later (oxygen uptake 1855 vs. 1459 ml/min; anaerobic threshold 920 vs. 790 ml/min; oxygen-pulse 10.6 vs. 8.0 ml/beat; oxygen partial pressure 77.5 vs. 67.6 mmHg; alveolar arterial oxygen difference 33 vs. 44 mm Hg). Further constant subjective and objective improvement in physical performance was demonstrated 3 months after embolization. This case confirms that embolization of a pulmonary arteriovenous fistula can rapidly achieve lasting improvement in exercise performance.

Adult↗
PubMed1993

Juvenile hereditary polyglucosan body disease with complete branching enzyme deficiency (type IV glycogenosis).

Polyglucosan body diseases in adults, contrary to infantile cases (Andersen's disease or type IV glycogenosis or amylopectinosis), are usually not associated with a significant deficiency of the branching enzyme (= amylo-1,4-1,6 transglucosidase). We, therefore, report on a 19-year-old male with complete branching enzyme deficiency presenting with severe myopathy, dilative cardiomyopathy, heart failure, dysmorphic features, and subclinical neuropathy. His 14-year-old brother had similar symptoms and was erroneously classified by a previous muscle biopsy as having central core disease but could later be identified as also having polyglucosan body myopathy. The skeletal muscle, endomyocardiac, and sural nerve biopsies as well as the autopsy revealed extraordinarily severe deposits of polyglucosan bodies not only in striated and smooth muscle fibers, but also in histiocytes, fibroblasts, perineurial cells, axons and astrocytes. Occasional paracrystalline mitochondrial inclusions were also noted. Thus, this patient represents to our knowledge the first juvenile, familial case of polyglucosan body disease with total branching enzyme deficiency and extensive polyglucosan body storage.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1993

[Do heart transplant patients benefit from rate-adjusted electrostimulation?].

Exercise capacity of heart transplant recipients is limited in comparison to normals and, due to cardiac denervation, exercise-induced heart-rate response is blunted in these patients. In order to evaluate the effect of rate-responsive atrial pacing on exercise capacity, 13 patients (three female, 10 male; age: 53 +/- 7 years) were studied 2-35 months after orthotopic heart transplantation. Spiroergometry with breath-to-breath gas analysis was performed during a progressive supine bicycle test with a starting workload of 25 watts and increments of 15 watts every minute. In comparison to 10 normals (two female, eight male; age: 51 +/- 7 years) maximal heart rate (127 +/- 17 vs. 146 +/- 12 min-1), maximal work load (107 +/- 27 vs. 208 +/- 42 watts) and oxygen consumption at the anaerobic threshold (9 +/- 2 vs. 18 +/- 4 ml/kg/min) were significantly reduced in heart transplant recipients (p < 0.05). During the exercise test the p-waves of the remaining part of the recipients' atria were registered via a transoesophageal catheter. The maximal rate of the innervated recipients sinus node (146 +/- 15 min-1) was equal to the maximal heart rate of the control group. The exercise protocol was repeated during atrial stimulation of the transplanted hearts. To achieve a physiological adaptation of the heart rate, the pacing rates were adjusted to the rates of the recipients sinus node. In comparison to the previous tests an improvement of cardiopulmonary exercise capacity was not observed during rate adaptive pacing.

Adult↗
PubMed1992

[Physical exercise tolerance in chronic obstructive emphysematous bronchitis and coronary heart disease under antiobstructive therapy].

19 consecutive patients (18 men, one woman, mean age 61.4 [49-73]years) with chronic obstructive airways disease (bronchitis and emphysema) together with angiographically confirmed coronary heart disease were studied to investigate their cardiopulmonary exercise tolerance and the effects of bronchodilators on their myocardial ischaemia. Because they were receiving drug therapy for angina or because they had previously undergone aortocoronary bypass operation or balloon dilatation, the patients were symptom-free. In three cases slight ischaemia was demonstrable during maximal exertion. Aerobic and anaerobic exercise capacity was determined by spiroergometry after inhalation of salbutamol (S, 0.2 mg) alone or in combination with oxitropium bromide (O, 0.2 mg). The supplementary effect of oral theophylline (T, 15 mg/kg.day) was studied in 13 patients. In terms of maximal aerobic exercise tolerance the following improvements were noted: energy output (watts): S: + 6.3%; S and O: + 12.3% (P < 0.05); S, O and T: + 14.0% (P < 0.01). Oxygen uptake (ml/min): S: + 8.2% (P < 0.05); S and O: + 18.2% (P < 0.01); S, O and T: + 35.4% (P < 0.01). Maximum exercise capacity was not significantly improved, although maximum oxygen uptake was significantly increased by the two-drug combination by 16.9% (P < 0.05) and by the three-drug combination by 19.2% (P < 0.05). Maximum minute volume and tidal volume rose significantly, though respiratory rate was unchanged. Heart rate and blood pressure remained practically unaffected by the treatment, both at rest and during exertion. There was no evidence of significant aggravation of ventricular arrhythmias or of ischaemia during ergometric testing.

Albuterol↗
PubMed1992

Clinical results of automatic slope adaptation in a dual sensor VVIR pacemaker.

Manual slope programming in rate adaptive pacemakers can be time consuming. This may become worse with dual sensor devices. The remedy is to let the pacemaker automatically learn the slopes. Fast learning replaces initial manual slope programming. Daily learning is a continuous process to determine and optimize slopes during daily life. Both methods are known for a QT sensing pacemaker. Fast learning is known for other single sensor devices. The aim of this study was to follow daily learning in a QT and activity dual sensor pacemaker, starting with factory slope settings. Six patients were studied for about 8 weeks. The daily learning algorithm appeared to be effective, showing the desired regulation processes. It took 2-5 weeks to reach full rate response.

Acceleration↗
PubMed1992

[Beta receptor blockers in dilated cardiomyopathy (clinical aspects)].

Results of 16 international published studies (with a total of 397 patients in NYHA-classes II-III) concerning chronic therapy with beta-adrenoceptor blockade in idiopathic dilated cardiomyopathy were analyzed. 8 studies were placebo controlled. Under beta-blockade cardiac output increased significantly by about 15% and ejection fraction by approximately 30%, apparently due to an improvement in contractility and relaxation of LV myocardium. Therapy was tolerated without complications in 93% of patients when the loading dose was 5 to 15 mg metoprolol/d (or equivalent) and a long-term dose of 100-200 mg/d metropolol (or equivalent) was reached within 4 weeks. Patients with severe heart failure (NYHA IV) had a higher risk of complications. A positive effect of beta-blockade in IDC was achieved in most cases but not earlier than after 2-3 months after initiating therapy. Despite these positive results beta-blockade in patients with IDC may not yet be recommended generally. Sufficient results of controlled trials are still lacking. Important questions with regard to the prognosis under beta-blockade, to the effects of cardioselectivity and intrinsic activity, and to the efficacy of this kind of therapy in the presence of ACE inhibitors have not been answered. Thus, major trials with controlled design are needed.

Adrenergic beta-Antagonists↗
PubMed1992

[Electrocardiographic diagnosis of acute graft rejection after heart transplantation].

In order to evaluate the diagnostic value of standard-ECG (ST-ECG) and precordial mapping-ECG with 63 unipolar leads (PM-ECG) for detection of acute cardiac allograft rejection, 15 patients (12 male, 3 female; age range 24-64 years) were studied. ST-ECG and PM-ECG were recorded along with 94 endomyocardial biopsies. Twenty-four acute rejections were detected histologically. Using the ST-ECG, a reduction of the QRS-amplitude-sum (lead I, II, III, V1 and V6) greater than or equal to 5% in comparison with the ECG obtained 1 week before was found to be the best diagnostic criterion (sensitivity 63%, specificity 74%, positive predictive value 48%, negative predictive value 85%). By analysing the PM-ECG a drop of the QRS-amplitude greater than or equal to 12% in greater than or equal to 14/63 precordial leads was determined to be the most reliable parameter (sensitivity 79%, specificity 71%, positive predictive value 49%, negative predictive value 91%). In contrast to the high sensitivity of PM-ECG, ST-ECG was less suitable for detection of acute rejection. However, taking into account the high negative predictive value of PM-ECG, acute rejection could be excluded with high probability, if the QRS-amplitudes of the PM-ECG remained stable. This may lead to a lower frequency of routinely performed endomyocardial biopsies.

Adult↗
PubMed1991

[Heart damage after electric injury].

Death from electrical accident due to low voltage (220 Volt/380 Volt) is usually caused by ventricular fibrillation. In humans who sustain non fatal electrical injury abnormal ECG findings due to myocardial damage are rare. 243 (76%) of 320 ECGs of survivors of an electrical accident were diagnosed as normal. In 42 patients (13%) unspecific electrographic changes were seen and in 35 (11%) abnormal ECGs were found. In comparison to findings in normal populations no significant accumulation of ECG changes was observed. A causal relationship between abnormal ECG findings and electrical accident is only then probable if ECG abnormalities are documented immediately after injury and serial ECG controls demonstrate significant changes in comparison to the initial abnormality.

Adolescent↗