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ABSTRACT: The term "coronary ectasia" describes the dilatation of one or more coronary artery segments with the signs of an impaired coronary blood flow. The prevalence, clinical significance and necessity of treatment of such a lesion is unclear.
Diagnostic coronary angiographies of 7101 patients (2131 women and 4970 men) were retrospectively evaluated for the presence of dilated coronary segments. Prevalence, age- and gender distribution, cardiovascular risk factors, clinical symptoms, CRP-concentrations, prevalence of myocardial infarction as well as the coronary morphology of patients with coronary ectasia were studied. The occurrence of myocardial infarction in this group was compared to that in a control group consisting of patients with stenotic coronary artery disease.
The prevalence of coronary ecstasy was 1.4 % (women: 0.56 %; men: 1.79 %), mean age of patients was 63.5 +/- 10.5 years. The right coronary artery was most frequently involved (RCA: 97 %, LAD: 30 %, RCX: 23 %, LCA: 35 %). In patients with one-vessel disease the right coronary artery was exclusively affected. In 85.1 % the dilatation of coronary segments was associated with stenotic coronary artery disease. 73.3 % of the patients with coronary ectasias suffered from angina, 33.7 % CCS (Canadian Cardiovascular Society) class III and IV. Angina in patients with coronary ecstasy did not differ from that of patients with stenotic coronary artery disease only. Patients with coronary ectasias had a higher incidence of myocardial infarction than patients with stenotic coronary heart disease (p < 0.001).
Coronary ectasia is a relatively rare entity and often associated with stenosis. Angina is a common symptom. Patients with coronary ectasias seem to suffer more frequently from myocardial infarctions than patients with only stenotic coronary heart disease.
DMW - Deutsche Medizinische Wochenschrift 11/2005; 130(42):2375-9. · 0.53 Impact Factor
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ABSTRACT: HISTORY: A 65-year-old woman was admitted because of dyspnea at rest and peripheral edema due to scleroderma-associated pulmonary fibrosis and hypertension, as well as Raynaud's phenomenon. DIAGNOSTIC FEATURES, TREATMENT AND COURSE: She had a marked restrictive ventilatory disorder with severe impairment of diffusion capacity. Right heart catheterization demonstrated a mean pulmonary artery pressure of 50 mmHg. She was able to walk only 220 m. All usual methods of treatment failed to give satisfactory results so that sildenafil (phospherodiesterase type-5 |PDE-5| inhibitor; Viagra ((R)) was given, even though it is not licensed for this indications ("off-label", as a therapeutic attempt. This achieved definite reduction in pulmonary arterial pressure and significantly improved the clinical symptoms. In particular, it drastically reduced the level of atrial natriuretic peptide, an important prognostic marker in right heart failure. Sildenafil also significantly raised peripheral perfusion and the signs of Raynaud's syndrome. CONCLUSION: PDE-5 inhibitors are efficacious in scleroderma-associated pulmonary hypertension and may also provide a new option in the treatment of Raynaud's disease.
DMW - Deutsche Medizinische Wochenschrift 09/2004; 129(33):1736-40. · 0.53 Impact Factor
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ABSTRACT: Genetic factors may be important in modifying heart size due to long-term athletic training. The significance of polymorphisms of genes of the renin-angiotensin system in myocardial mass in a population of athletes participating in different disciplines is not known.
The angiotensin I-converting enzyme gene insertion/deletion (I/D) polymorphism, angiotensinogen gene M235T polymorphism and angiotensin II type 1 receptor gene A1166C polymorphism were determined in 83 male Caucasian endurance athletes and associated with left ventricular mass.
No association with left ventricular mass was found for the polymorphisms of angiotensin I-converting enzyme gene I/D, angiotensinogen gene M235T and angiotensin II type 1 gene A1166C when studied separately. However, combined analysis of the angiotensin I-converting enzyme gene I/D polymorphism and angiotensinogen gene M235T polymorphism genotypes suggested an association with left ventricular mass (g m(-2)) (P = 0.023). Athletes with the angiotensin I-converting enzyme gene DD/angiotensinogen gene TT genotype combination had greater left ventricular mass compared with all other genotype combinations (179.8 +/- 26.1 g m(-2) vs. 145.2 +/- 27.3 g m(-2), P = 0.003).
These results suggest an association of combined angiotensin I-converting enzyme gene I/D polymorphism genotypes, and angiotensinogen gene M235T polymorphism genotypes with left ventricular hypertrophy due to long-term athletic training. A synergistic effect of angiotensin I-converting enzyme gene DD genotype and angiotensinogen gene TT genotype on left ventricular mass in endurance athletes appears to occur.
European Journal of Clinical Investigation 11/2001; 31(10):836-42. · 3.02 Impact Factor
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ABSTRACT: The risk of thromboembolic complications in patients with heart failure and/or chronic left-ventricular systolic dysfunction is increased. Nevertheless, anticoagulant therapy in these patients is still a subject of debate. Atrial fibrillation is the only prospectively evaluated, proven thromboembolic risk factor and patients with atrial fibrillation benefit from long term anticoagulant therapy. The significance of other proposed thromboembolic risk factors in heart failure and/or chronic left-ventricular dysfunction such as gender, cause of myocardial disease, severity of heart failure, left-ventricular ejection fraction, left-ventricular thrombus, left ventricular aneurysm and history of previous thromboembolic event is less clear. This article summarizes key studies, assesses the incidence of thromboembolism, evaluates risk factors and proposes guidelines for anticoagulation of patients with heart failure and/or left ventricular systolic dysfunction.
European Journal of Heart Failure 01/2001; 2(4):355-63. · 4.90 Impact Factor
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Der Internist 04/2000; 41(3):276-82. · 0.30 Impact Factor
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European Journal of Heart Failure 04/2000; 2(1):3-4. · 4.90 Impact Factor
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ABSTRACT: Das thromboembolische Risiko von Patienten mit Herzinsuffizienz aufgrund chronischer linksventrikulärer Dysfunktion ist erhöht.
Bei der Indikationsstellung zu einer oralen Dauerantikoagulation muß das Thromboembolierisko gegenüber den möglichen Blutungskomplikationen
einer solchen Therapie abgewogen werden.
Da es keine prospektive kontrollierte Studie gibt, die den Effekt einer oralen Dauerantikoagulation bei Patienten mit Herzinsuffizienz
aufgrund chronischer linksventrikulärer Dysfunktion untersucht hätte, wird die Indikation zur Antikoagulation bei diesen Patienten
kontrovers diskutiert und unterschiedlich gehandhabt. Die folgende Übersicht gibt den heutigen Kenntnisstand wider und leitet
daraus Empfehlungen für eine orale Antikoagulation bei Patienten mit Herzinsuffizienz und/oder chronischer linksventrikulärer
Dysfunktion ab.
Der Internist 02/2000; 41(3):276-282. · 0.30 Impact Factor
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ABSTRACT: Three young men became ill one after the other with fever, headaches, vomiting, arthralgias and muscle pain. One day after beginning of symptoms all three patients developed a haemorrhagic rash with petechial and ecchymotic lesions most intense on distal extremities. 24 hours later patient no. 1 and 3 were in septic shock.
Laboratory tests showed signs of systemic infection, disseminated intravascular coagulation and renal failure. On the day of admission to the hospital blood cultures showed Neisseria meningitidis in patient no. 1 and 3. In patient no. 2 blood cultures were negative.
Intravenous antibiotic therapy was started immediately after admission. In patient no. 1 and 3 purpura fulminans with multiple organ failure demanded intensive care treatment. Patient no. 1 recovered. Necrotic toes made amputations necessary. Patient no. 2 was never critically ill. Patient no. 3, whose course was complicated by a long lasting disseminated intravascular coagulation, died from massive cerebral bleeding 6 days after admission. Patient no. 2, who was treated with ciprofloxacin after symptoms began was never critically ill.
Neisseria meningitidis sepsis has a high mortality rate. Rapid admission to the hospital and beginning of an antibiotic therapy with penicillin G or a third-generation cephalosporin is a priority when meningococcal disease is suspected. Chemoprophylaxis should be offered to close contacts of patients.
DMW - Deutsche Medizinische Wochenschrift 05/1999; 124(14):424-8. · 0.53 Impact Factor
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DMW - Deutsche Medizinische Wochenschrift 07/1998; 123(23):748-9. · 0.53 Impact Factor
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ABSTRACT: In mononuclear leukocytes (MNL) of renal transplant recipients treated with cyclosporine A and prednisone, an increase of basal cAMP generation has been observed. In order to characterize the mechanisms underlying changes of cAMP generation in patients who were treated with immunosuppressives following heart transplantation, we investigated the beta-adrenoceptor--G protein--adenylate cyclase signal transduction cascade in heart transplant recipients and for comparison in renal transplant recipients as well as controls. Basal cAMP formation in MNL was elevated in heart transplant recipients by 272% and in renal transplant recipients by 148% compared to controls. Following beta-adrenoceptor stimulation with isoprenaline, cAMP formation in MNL of heart transplant recipients was similar to the controls, but was enhanced in renal transplant recipients to 138%. Investigation of beta-adrenoceptor density on MNL as a possible cause for increased cAMP formation revealed similar receptor numbers in controls and in cardiac or renal transplant recipients. Furthermore, the increase of the beta-adrenoceptor density on MNL, which is observed following infusion of isoprenaline, was similar in controls and heart transplant recipients. The amount of pertussis- and cholera toxin substrates was the same in heart transplant recipients as in controls. In contrast, MNL of renal transplant recipients showed a marked increase of Gs alpha by 45% and a smaller albeit significant increase of Gi alpha by 15%, as judged by cholera toxin and pertussis toxin labeling, respectively. Investigation of inotropic parameters by echocardiography under control conditions and during the infusion of increasing concentrations of isoprenaline revealed no difference in the basal contractility and the inotropic response to beta-adrenergic stimulation in controls and heart transplant recipients. It is concluded that changes of G-protein expression are involved in the increase of the cAMP-generation in MNL of heart transplant recipients. These alterations in MNL cannot be taken as a model of cellular function in the transplanted heart, but it is reasonable to suggest that elevations of cAMP formation in MNL may contribute to the immunosuppressive effects of the treatment with cyclosporine A or corticosteroids, the mechanism of which could be an alteration of Gs alpha or the catalyst in renal transplant recipients and the catalyst in heart transplant recipients which occurs without any changes of beta-adrenoceptors.
Research in Experimental Medicine 02/1994; 194(2):81-96.
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ABSTRACT: 1. The present study was designed to characterize the positive inotropic response to DPI 201-106 in isolated papillary muscle strips obtained from heart failure patients undergoing surgery. 2. The positive inotropic responses to isoprenaline and milrinone and cardiac beta-adrenoceptor density were also determined. 3. DPI 201-106 increased the force of contraction in papillary muscle strips from patients with moderate (NYHA II-III) and severe (NYHA IV) heart failure, in a concentration-dependent manner. This positive inotropic effect was more pronounced in tissues from NYHA IV patients. Furthermore, these responses were greater than those produced by milrinone or isoprenaline. The positive inotropic effects of isoprenaline and milrinone were reduced in NYHA IV compared to NYHA II-III. Consistently, there was also a smaller density of beta-adrenoceptors in myocardium from NYHA IV than in NYHA II-III. The positive inotropic effect of Ca2+ was similar in tissues from both groups of patients. 4. The positive inotropic effect of DPI 201-106 was not antagonized by adenosine or carbachol, whereas both compounds reduced the positive inotropic effect of isoprenaline. 5. DPI 201-106 did not increase the Ca2+ -sensitivity of chemically skinned ventricular fibres, whereas a significant increase of the Ca2+ -sensitivity was obtained with trifluoperazine. 6. It is concluded that DPI 201-106 produces significant positive inotropic effects in tissue excised from the failing human heart. The lack of inhibition by adenosine and carbachol might contribute to its greater effectiveness in NYHA IV than NYHA II-III and indicates that its mechanism of action is cyclic AMP-independent. A sensitization of the contractile proteins to Ca2+ does not appear to be important for the positive inotropic action of DPI 201-106 in the failing human heart.
British Journal of Pharmacology 10/1989; 98(1):275-83. · 4.41 Impact Factor
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ABSTRACT: The present study was designed to elucidate whether or not the positive inotropic effects of isoprenaline, milrinone, and DPI 201-106 in myocardial tissue from various sources reveal reliable results for the failing human heart. Therefore, in vitro positive inotropic responses were studied in human papillary muscle strips from patients with moderate heart failure (NNYHA II-III), human atrial trabeculae (HAT), isolated papillary muscles from Wistar-Kyoto rats (WK), and from spontaneously hypertensive rats (SHR). Results were compared with the effects of the compounds in papillary muscle strips from patients with severe heart failure (NYHA IV). In NYHA IV, positive inotropic responses were smaller for isoprenaline and milrinone than in NYHA II-III. The response to DPI 201-106 was more pronounced. In HAT, the effects of isoprenaline and milrinone were greater than in NYHA IV. The positive inotropic effect of DPI 201-106 was similar. In SHR, only the positive inotropic effect of isoprenaline was smaller than in WK. The effects of DPI 201-106 and milrinone did not differ. These data show that inotropic responses in NYHA II-III, HAT, WK, and SHR differ from the severely failing myocardium. It is concluded that new positive inotropic agents should be screened in human myocardial tissue from patients with heart failure, as experimental results from other sources may be irrelevant in this respect.
Journal of Pharmacological Methods 04/1989; 21(1):33-44.
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ABSTRACT: The positive inotropic responses to isoprenaline, dobutamine, histamine, forskolin, isobutyl-methylxanthine (IBMX), dibutyryl-cyclic adenosine monophosphate (db-cAMP), ouabain and calcium were studied in isolated, electrically driven papillary muscle strips from either terminally failing human hearts or non-failing donor myocardium. The positive inotropic effect of calcium has been taken to evaluate the maximal force of contraction of each individual muscle strip ('contractile reserve'). In the non-failing heart, the maximal positive inotropic effect of isoprenaline, dobutamine, IBMX, ouabain and calcium were not significantly different, but were significantly greater than histamine. In terminally failing hearts, the positive inotropic effects of agents stimulating the adenylate cyclase by a receptor-dependent mechanism (isoprenaline, dobutamine and histamine) and the phosphodiesterase inhibitor IBMX are less than in the normal heart. Furthermore, these compounds gave a markedly reduced inotropic effect compared with forskolin, db-cAMP and ouabain, which gave maximal responses similar to calcium in the failing hearts. The data did not differ when the increase of force of contraction was related to the diameter of each preparation. These results indicate that a defect in adenylate cyclase occurs in the failing human heart, presumably located at the regulatory stimulatory subunit (Gs) of the adenylate cyclase since effects through stimulatory receptors were reduced. Responses from activation of the catalytic subunit or through cAMP-dependent protein kinases were less affected. Since the positive inotropic effect of IBMX is also impaired, it is suggested that the basal rate of cAMP production is also reduced in heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
European Journal of Clinical Investigation 01/1989; 18(6):600-6. · 3.02 Impact Factor
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ABSTRACT: The number of cardiac beta-adrenoceptors and the positive inotropic effect of isoprenaline and milrinone were measured in cardiac membranes and isolated, electrically driven muscle strips from nonfailing donor hearts and from patients with mitral valve disease (NYHA II-III), ischemic heart disease, and dilated cardiomyopathy (NYHA IV). In nonfailing hearts, the number of beta-adrenoceptors were 41.5 fmol/mg protein (mean, n = 3). In ischemic heart disease and NYHA II-III, there was a loss of cardiac beta-adrenoceptors (22.1 fmol/mg protein, mean, n = 3; 23.2 +/- 2.7 fmol/mg protein, n = 30), respectively. In NYHA IV, there was a pronounced reduction of the number of cardiac beta-adrenoceptors to 12.1 +/- 1.5 fmol/mg protein (n = 15). The Kd value did not differ in either group. Correspondingly, the positive inotropic effect of isoprenaline was more pronounced in nonfailing myocardium, reduced in NYHA II-III and ischemic heart disease and almost blunted in NYHA IV. Similar results were observed with the phosphodiesterase inhibitor milrinone. A good correlation of the beta-adrenoceptor density to the maximal positive inotropic effect of isoprenaline and milrinone was observed. Neither the number of cardiac beta-adrenoceptors nor the positive inotropic effect of isoprenaline correlated with the age of the patients. We conclude that the number of cardiac beta-adrenoceptors and the positive inotropic effect of beta-adrenoceptor agonists are reduced in the failing human heart depending on the severity of heart failure. Furthermore, the positive inotropic effect of milrinone is also reduced and related to the reduction of beta-adrenoceptors. The lack of correlation with the age of the patients provides evidence for a predominant role of heart disease rather than aging in the reduction of beta-adrenoceptors and subsensitivity to cyclic AMP-increasing positive inotropic agents in the failing human heart.
Journal of Cardiovascular Pharmacology 01/1989; 12(6):726-32. · 2.29 Impact Factor
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ABSTRACT: The positive inotropic effect of milrinone was investigated in isolated, electrically driven (1 Hz) human papillary muscle strips from nonfailing myocardium (control) and from patients with moderate (NYHA II-III) and severe (NYHA IV) heart failure. In the control hearts, milrinone increased force of contraction to about the same degree as Ca2+ at 15 mmol/l. In NYHA II-III, the positive inotropic effect was significantly reduced compared with the control hearts. In NYHA IV, the effectiveness (maximal increase in force of contraction) and potency (as judged from the EC50 values) were significantly less than in NYHA II-III and controls. Preexposure of the preparations to isoprenaline in NYHA II-III and NYHA IV shifted the concentration-response curve for milrinone to the left and, moreover, restored the effectiveness of the compound (i.e., similar positive inotropic effect as Ca2+). No difference in the cAMP-phosphodiesterase inhibition by milrinone could be detected between controls, NYHA II-III, and NYHA IV. It is concluded that diminished basal cAMP production is responsible for reducing the effectiveness of milrinone in the failing human heart. A diminished inhibition of cAMP-phosphodiesterase does not play a role. The fact that stimulation of cardiac beta-adrenoceptors increased the effectiveness of milrinone provides evidence that combined application of catecholamines and phosphodiesterase inhibitors may be useful in the treatment of patients with terminal heart failure.
Klinische Wochenschrift 11/1988; 66(19):957-62.
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ABSTRACT: The effects of isoprenaline, Ca2+ and phenylephrine (in the presence of propranolol) on force of contraction were studied in isolated electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and age-matched (14-18 weeks) Wistar Kyoto control rats (WK). Cardiac alpha- and beta-adrenoceptors were characterized by radioligand binding studies. The positive inotropic effect of isoprenaline in SHR was less effective than in control rats. The EC50 values did not differ in both groups. In SHR, isoprenaline was less effective than Ca2+ to increase force of contraction whereas in WK it had the same effectiveness as Ca2+. The positive inotropic effect of phenylephrine in the presence of propranolol was similar in SHR and WK. In SHR, both the densities of cardiac alpha- and beta-adrenoceptors were reduced. In beta-adrenoceptor binding experiments, the nonhydrolysable GTP analog Gpp(NH)p caused a rightward shift of agonist competition curves of isoprenaline. Biphasic competition curves revealed a similar percentage of low and high affinity sites in SHR and WK, respectively. In alpha-adrenoceptor binding experiments, Gpp(NH)p caused no detectable shift of agonist competition curves with norepinephrine. It is suggested that cardiac beta-adrenoceptor down-regulation is involved in the reduced positive inotropic effect of isoprenaline in SHR. Functional uncoupling of beta-adrenoceptors does not appear to be involved in the reduced beta-adrenoceptor-mediated positive inotropism in SHR. Binding studies do not show evidence for a large number of alpha-adrenoceptors coupling to a guanine-nucleotide binding protein in the rat heart. Finally, in ventricular myocardium of SHR, cardiac alpha-adrenoceptors do not serve as a reserve mechanism during impaired beta-adrenergic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Archiv für Experimentelle Pathologie und Pharmakologie 11/1988; 338(4):383-91. · 2.65 Impact Factor
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ABSTRACT: Experiments were designed to characterize cardiac alpha-adrenoceptors and the alpha-adrenoceptor-mediated positive inotropic effects in human myocardial tissue from patients with moderate New York Heart Association (NYHA) class II-III and severe (NYHA class IV) heart failure. The number of cardiac alpha-adrenoceptors was low but similar in moderate and severe heart failure (NYHA class II-III: 6.7 +/- 0.8 fmol/mg protein 3H-prazosin bound, n = 12; NYHA class IV: 7.4 +/- 0.9 fmol/mg protein 3H-prazosin bound, n = 9; NS). Correspondingly, the alpha-adrenoceptor-mediated positive inotropic effect (phenylephrine in the presence of propranolol) did not significantly differ in both groups. In the same hearts, the number of beta-adrenoceptors was measured. The number of beta-adrenoceptors was significantly reduced in severe heart failure (NYHA class II-III: 22.0 +/- 1.5 fmol/mg protein 3H-CGP 12177 bound, n = 12; NYHA class IV: 11.9 +/- 0.8 fmol/mg protein 3H-CGP 12177 bound, n = 9; p less than 0.05). The positive inotropic effect of isoprenaline was significantly reduced in NYHA class IV. The positive inotropic effect of Ca2+ was similar in both groups. In conclusion, cardiac beta-adrenoceptors and the beta-adrenoceptor-mediated positive inotropic effects were reduced in severely failing myocardium. Cardiac alpha-adrenoceptors and the positive inotropic effect resulting from their stimulation is unchanged. Therefore, down regulation in response to increased sympathetic stimulation or a compensatory increase of alpha-adrenoceptors does obviously not occur in the human heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Cardiovascular Pharmacology 10/1988; 12(3):357-64. · 2.29 Impact Factor
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ABSTRACT: The positive inotropic effect of DPI 201-106 has been studied in isolated, electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WK). The positive inotropic effect of isoprenaline (Iso) and Ca2+ was studied for comparison. The maximal positive inotropic effect of Iso was less in SHR than in WK. In SHR, DPI 201-106 more effectively increased force of contraction than Iso. The positive inotropic effects of DPI 201-106 and Ca2+ were not different in SHR and WK. The EC50 values of DPI 201-106, Iso, and Ca2+ did not differ in either group. Furthermore, adenosine and carbachol reduced the positive inotropic effect of Iso but failed to exert a negative inotropic action when force of contraction has been increased with DPI 201-106. The isoprenaline-antagonistic effect of adenosine and carbachol was not different in SHR and WK. We conclude that DPI 201-106 might be an effective positive inotropic agent in states in which adrenergic function is compromised. The lack of inhibition by adenosine or m-cholinoceptor agonists could contribute to the effectiveness of the compound to increase myocardial force of contraction.
Journal of Cardiovascular Pharmacology 05/1988; 11(4):461-7. · 2.29 Impact Factor
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ABSTRACT: In the present study, h-ANF failed to reduce myocardial force of contraction alone and in the presence of isoprenaline. This lack of effect was observed in electrically driven, isolated human papillary muscle strips and rat papillary muscles. In contrast, adenosine and carbachol exerted antiadrenergic actions in rat and human myocardium. It is concluded that h-ANF obviously does not play a role in the regulation of human and rat myocardial force of contraction, whereas adenosine and carbachol are capable to produce antiadrenergic effects in the human and rat myocardium.
Life Sciences 02/1988; 43(16):1261-7. · 2.53 Impact Factor
