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R H Schwinger

Publications and source records attributed to R H Schwinger.

At least 19 recordsLinked to original sources
PubMed2006

[Short and long-term results of balloon mitral valvotomy].

BACKGROUND: Since its introduction in the eighties by Inoue, percutaneous balloon valvotomy has been established as treatment of choice for symptomatic degenerative mitral stenosis. Especially young patients with rheumatic fusion of the mitral commissures and no calcification of the still pliable valve leaflets are candidates for this procedure. In these patients balloon valvotomy is expected to give results comparable or even superior to operative commissurotomy. PATIENTS AND METHODS: This report presents the short and long-term results of 33 patients (24 females, 9 males; median age: 53 years) that underwent percutaneous mitral valvotomy (PMV) at the cardiac unit of the university hospital in Cologne during the last three years. RESULTS: The intervention was immediately successful in 31 patients (94%). The median mitral valve area was increased after PMV to 2.0 +/- 0.5 cm(2) an increase of mean opening area of 82% and a decrease of mean pressure gradient by about 50%. Follow-up date at 12 and 24 months were available for 21 and 12 patients, respectively. During the first 12 months after intervention four patients subsequently had to have surgical mitral valve replacement, one of them together with a coronary artery bypass graft. One patient, who had undergone PMV in cardiogenic shock died after the intervention. A 12-month follow-up demonstrated a mean mitral valve area of 1.7 +/- 0.4 cm(2) as assessed by echocardiography. After 24 months comparable mean valve area was 1.7 +/- 0.4 cm(2). One other patient required operative valve replacement, but there were no further deaths. CONCLUSION: The data collected from this very heterogeneous group of patients at the cardiac unit of the university hospital in Cologne confirms the observation that PMV is beneficial in young patients with favorable valve morphology and shows that it is indicated not only as a palliative measure but also as treatment option in older patients with more complex alterations of the mitral valve.

Catheterization↗
PubMed2005

[Typical angina pectoris complaints without coronary macroangiopathy].

HISTORY AND CLINICAL FINDINGS: A 46-year-old patient with repetitive chest pain on exercise and exclusion of coronary heart disease was transferred for further diagnostic evaluation and therapy because of the suspicion of cardiac syndrome X. INVESTIGATIONS: Coronary angiography showed no evidence for a stenotic coronary heart disease. However, a decreased coronary blood flow reserve was detected upon adenosin treatment (RCA), and myocardial scintigraphy (single-photon emission tomography-investigation [SPECT]) revealed a perfusion defects in the inferior wall. TREATMENT AND COURSE: Endothelial dysfunction (syndrom X) was diagnosed and an optimised therapy regime was initiated in order to improve endothelial function. CONCLUSION: In patients with typical angina pectoris and positive treadmill exercise stress test in the absence of stenotic coronary heart disease, cardiac syndrome X should be considered, and further invasive- and non-invasive tests should be performed. Therapeutic goals should be to improve endothelial function and to control chest pain and improve quality of life.

Chest Pain↗
PubMed2005

Risk stratification models fail to predict hospital costs of cardiac surgery patients.

BACKGROUND: The aim of this prospective study was to determine if commonly used risk stratification models can predict total hospital costs in cardiac surgical patients. METHODS: Between October 1st and December 31st 2003, all consecutive adult patients undergoing cardiac surgery on CPB at our institution were classified using seven risk stratification scoring systems: EuroSCORE, Cleveland, Parsonnet, Ontario, French, Pons, and CABDEAL. Total hospital costs for each patient were calculated on a daily basis including preoperative diagnostic tests, operating room costs, disposable materials, drugs, blood components, costs for personnel, and hospital fixed-costs. Linear regression analysis was used to determine the correlation between costs and the seven risk stratifications models as well as length of stay (LOS) on ICU. The Spearman correlation coefficient was calculated from the regression line, and an analysis of residuals was performed to determine the quality of the regression. RESULTS: A total of 252 patients were operated for CABG (n=175), valve (n=39), CABG plus valve (n=21), thoracic aorta (n=13) and miscellaneous (2 myxoma, 1 ASD, 1 pulmonary embolism). Mean age of the patients was 66.0+/-11.4 years, 29.4% were female. LOS on ICU was 3.3+/-6.3 days and the 30-day mortality rate was 6.7%. Spearman correlation between the seven risk stratification models and hospital costs was below r=0.32 (p=0.0001), but was r=0.94 (p=0.0001) between ICU LOS and costs. CONCLUSIONS: Total hospital costs can be identified by length of ICU stay. None of the common risk stratification models accurately predicted total hospital costs in cardiac surgical patients.

Aged↗
PubMed2001

Nebivolol, carvedilol and metoprolol do not influence cardiac Ca(2+) sensitivity.

It has been argued that some beta-adrenoceptor antagonists may directly influence myofibrillar cross-bridge interaction in cardiac skinned fiber preparations of animal models. The present study investigates the effects of nebivolol, metoprolol and carvedilol on tension development of Triton X-100 skinned fibers obtained from human failing myocardium as well as on force of contraction and intracellular Ca(2+) transient in isolated trabeculae. In skinned fiber preparations, none of the beta-adrenoceptor antagonists (10 microM) influenced Ca(2+) sensitivity of tension development or maximal Ca(2+) activated tension (DT(max)): control: EC(50) for Ca(2+): 1.28+/-0.05 microM, DT(max): 14.09+/-0.59 mN/mm(2); nebivolol: 1.36+/-0.1 microM, 14.14+/-0.95 mN/mm(2); carvedilol: 1.32+/-0.11 microM, 13.83+/-0.90 mN/mm(2); metoprolol: 1.34+/-0.14 microM, 13.72+/-0.36 mN/mm(2). Simultaneous measurement of force and Ca(2+) transient in the presence of the beta-adrenoceptor antagonists (3 microM) showed that the decrease in force of contraction was paralleled by a similar decrease in the intracellular Ca(2+) transient. In conclusion, none of the investigated beta-adrenoceptor antagonists influenced Ca(2+) sensitivity of myofibrillar tension development in human failing myocardium.

Adrenergic beta-Antagonists↗
PubMed2001

Increased expression of isoform 1 of the sarcoplasmic reticulum Ca(2+)-release channel in failing human heart.

BACKGROUND: The sarcoplasmic reticulum (SR) Ca(2+)-release channel plays a key role in the excitation-contraction coupling of cardiac myocytes. Because respective alterations have been reported in human heart failure, we investigated isoform expression of the SR Ca(2+)-release channel in human hearts from patients with terminal heart failure (dilated cardiomyopathy [DCM], n=8) and nonfailing organ donors (NF, n=8). METHODS AND RESULTS: Expression of mRNA of SR Ca(2+)-release channel isoforms in isolated human cardiomyocytes and myocardial tissue was analyzed by reverse-transcription polymerase chain reaction. Protein expression was quantified in myocardial tissue with [(3)H]-ryanodine binding and with Western blots, expressed as densitometric units per microgram of protein (DU), and cellular localization was visualized with immunohistochemistry. We found mRNA expression of isoforms 1, 2, and 3 in cardiomyocytes and myocardial tissue both in NF and DCM. Total SR Ca(2+)-release channel protein expression in NF (B(max) 2.16+/-0.43 pmol/mg protein) and in DCM (B(max) 2.33+/-0.22 pmol/mg protein) myocardium was unchanged. Expression of isoform 1 of the SR Ca(2+)-release channel was significantly (P=0.0037) increased in DCM myocardium (NF 1.97+/-0.25 versus DCM 3.37+/-0.31 DU), whereas protein expression of isoform 2 (NF 14.62+/-0.87 versus DCM 13.52+/-0.43 DU) and isoform 3 (NF 1.39+/-0.13 versus DCM 1.35+/-0.19 DU) was unchanged. All 3 isoforms of the protein could be localized in human ventricular myocytes with fluorescence immunohistochemistry. CONCLUSIONS: All 3 isoforms of the SR Ca(2+)-release channel were determined in human ventricular cardiomyocytes. Increased expression of isoform 1 of the SR Ca(2+)-release channel could contribute to impaired excitation-contraction coupling in human heart failure.

Adult↗
PubMed2001

[Angiographically unexplained myocardial ischemia in high grade coronary stenosis with main stem involvement in intravascular ultrasound].

HISTORY AND ADMISSION FINDINGS: For seven weeks a 57-year-old man had been complaining of recurrent non-radiating retrosternal pain and pressure on slightest exertion. Admission physical examination was unremarkable except for evidence of peripheral vascular disease. Cardiovascular risk factors were hypertension, hyperlipoproteinaemia and obesity. INVESTIGATIONS: The resting ECG was unremarkable. Objective signs of myocardial ischaemia were produced in the exercise ECG (angina at 100 Watt, negative T waves in V2 to V6 and borderline S-T depression in V4). Myocardial scintigraphy showed reversible reduced perfusion of the anterior wall near the apex and also of the apex and septum. Left ventricular (LV) angiography demonstrated a normally contracting LV, while selective coronary angiogram revealed a 20% reduction in caliber of the proximal branch of the anterior interventricular branch (AIVB), with otherwise normal coronary arteries. Subsequent intravascular ultrasound (IVUS) showed a circular echo-poor 80% stenosis at the origin of the AIVB with extension to the main stem. TREATMENT AND COURSE: A bypass from the internal mammary artery to the AIVB and an aortocoronary venous bypass to the intermediate branch were performed. The patient was free of symptoms postoperatively. CONCLUSION: If cases where there is a discrepancy between clinical and coronary angiographic findings--the latter being unclear or inconsistent, especially in the area of the left main stem, bifurcations or vessel origin--IVUS may contribute decisively to demonstrating coronary anatomy or pathology, and to indicating the type of revascularizing measures.

Coronary Angiography↗
PubMed2001

[The Ca(2+) sensitizers CGP 48506 and EMD 57033, but not the Na(+) channel modulator BDF 9148, prolong relaxation in isolated cardiomyocytes of the guinea pig].

The sodium channel modulator DPI 201-106 has been described to posses Ca(2+)-sensitizing properties. Therefore, the present study investigated the inotropic effect of the Na(+)-channel modulator BDF 9148 (1 microM), a congener of DPI 201-106, in comparison with the Ca(2+)-sensitizers CGP 48506 (1-50 mumol/l) and EMD 57033 (1-30 mumol/l) in electrically driven left ventricular cardiomyocytes isolated from guinea pigs. The changes of the contraction amplitude in comparison to the basal cell shortening (cell shortening in micron and %) were continuously recorded with a one-dimensional high speed camera. BDF 9148, CGP 48506, and EMD 57033 exerted a significant increase in the contraction amplitude (p < 0.05 vs. control). The maximal positive inotropic effects of CGP 48506 (50 mumol/l) and EMD 57033 (30 mumol/l) were +249 +/- 30% and +226 +/- 28%, respectively. The corresponding value for BDF 9148 (1 mumol/l) was +176 +/- 16%. However, only the Ca(2+)-sensitizers CGP 48506 and EMD 57033, but not BDF 9148, prolonged the contractile twitch. Especially in patients with an already enhanced intracellular myocardial Ca(2+)-concentration, Ca(2+)-sensitizers, which impair relaxation, may be disadvantageous for therapeutical use despite their positive inotropic effect.

Animals↗
PubMed2001

Nebivolol, bucindolol, metoprolol and carvedilol are devoid of intrinsic sympathomimetic activity in human myocardium.

1. The present study investigated whether or not there may be differences in the direct cardiac actions of the novel, highly beta(1)-selective adrenoceptor antagonist nebivolol (NEB) in comparison to metoprolol (MET), bisoprolol (BIS), carvedilol (CAR) and bucindolol (BUC) in human myocardium (n=9). 2. The rank order of beta(1)-selectivity as judged by competition experiments to (3)H-CGP 12.1777 in the presence of CGP 207.12 A (300 nmol l(-1), K(i)beta(2)) or ICI 118.551 (50 nmol l(-1), K(i)beta(1)) were NEB(K(i)beta(2)/K(i)beta(1): 40.7) > BIS(15.6) > MET(4.23) > CAR(0.73) > BUC(0.49). 3. The rank order of the negative inotropic potency of the beta-adrenoceptor antagonists measured in left ventricular trabeculae (dilated cardiomyopathy, DCM) as judged by the concentration needed to induce a 50% decrease in isoprenaline (1 micromol l(-1))-stimulated force (IC(50)) was: MET (0.6 micromol l(-1)) > CAR (4.1 micromol l(-1)) > NEB (7.0 micromol l(-1)). 4. NEB, BUC, MET and CAR did not not exert an intrinsic sympathomimetic activity (ISA) as determined by measurements of force development in forskolin (0.3 micromol l(-1)) pre-treated left ventricular trabeculae, nor by measuring adenylate cyclase activity in forskolin (0.3 micromol l(-1))-stimulated assays (crude membranes). This also holds true for radioligand binding assays with or without guanine nucleotide guanyl-5'-yl imidodiphosphate (Gpp(NH)p). 5. Although all studied beta-adrenoceptor antagonists lack intrinsic sympathomimetic activity (ISA), they differ in the beta(1)-selectivity as well as in their direct negative inotropic action. These differences as well as the mode of extracardiac action may have an impact on outcome of patients treated with beta-adrenoceptor antagonists.

Adrenergic beta-Antagonists↗
PubMed2001

Force/shortening-frequency relationship in multicellular muscle strips and single cardiomyocytes of human failing and nonfailing hearts.

BACKGROUND: Force of contraction (FOC) frequency-dependently increases in multicellular muscle strip preparations of human nonfailing myocardium, whereas FOC declines in human failing myocardium with increasing stimulation frequency. We investigated whether these characteristics can be observed in single isolated myocytes. METHODS AND RESULTS: Isolated multicellular muscle strip preparations and single isolated cardiomyocytes of failing (heart transplants, dilative cardiomyopathy; n = 11) and nonfailing (donor hearts; n = 11) human hearts were studied. The changes in contraction amplitude (cell shortening in micrometers) at increasing frequency of stimulation (0.5-2 Hz) were continuously recorded with a 1-dimensional high-speed camera that detected the cell edges and measured their distance during contraction. The increase in stimulation frequency was associated with a significant decrease in FOC (2 v 0.5 Hz; 68% basal) and a decrease in cell shortening of human left ventricular cardiomyocytes from failing hearts (2 v 0.5 Hz; 65% basal). In contrast, in human nonfailing myocardium, contraction increased at increasing stimulation frequencies (2 v 0.5 Hz; FOC, 180% basal; cell shortening, 129% basal). CONCLUSIONS: The negative force-frequency relationship measured in multicellular preparations of failing human myocardium results from alterations at the single cell level.

Cardiomyopathy, Dilated↗
PubMed2001

Loss of annexin A7 leads to alterations in frequency-induced shortening of isolated murine cardiomyocytes.

Annexin A7 has been proposed to function in the fusion of vesicles, acting as a Ca(2+) channel and as Ca(2+)-activated GTPase, thus inducing Ca(2+)/GTP-dependent secretory events. To understand the function of annexin A7, we have performed targeted disruption of the Anxa7 gene in mice. Matings between heterozygous mice produced offspring showing a normal Mendelian pattern of inheritance, indicating that the loss of annexin A7 did not interfere with viability in utero. Mice lacking annexin A7 showed no obvious phenotype and were fertile. To assay for exocytosis, insulin secretion from isolated islets of Langerhans was examined. Ca(2+)-induced and cyclic AMP-mediated potentiation of insulin secretion was unchanged in the absence of annexin A7, suggesting that it is not directly implicated in vesicle fusion. Ca(2+) regulation studied in isolated cardiomyocytes, showed that while cells from early embryos displayed intact Ca(2+) homeostasis and expressed all of the components required for excitation-contraction coupling, cardiomyocytes from adult Anxa7(-/-) mice exhibited an altered cell shortening-frequency relationship when stimulated with high frequencies. This suggests a function for annexin A7 in electromechanical coupling, probably through Ca(2+) homoeostasis.

Animals↗
PubMed2001

Ouabain and substrate affinities of human Na(+)-K(+)-ATPase alpha(1)beta(1), alpha(2)beta(1), and alpha(3)beta(1) when expressed separately in yeast cells.

Human Na(+)-K(+)-ATPase alpha(1)beta(1), alpha(2)beta(1), and alpha(3)beta(1) heterodimers were expressed individually in yeast, and ouabain binding and ATP hydrolysis were measured in membrane fractions. The ouabain equilibrium dissociation constant was 13-17 nM for alpha(1)beta(1) and alpha(3)beta(1) at 37 degrees C and 32 nM for alpha(2)beta(1), indicating that the human alpha-subunit isoforms have a similar high affinity for cardiac glycosides. K(0.5) values for antagonism of ouabain binding by K(+) were ranked in order as follows: alpha(2) (6.3 +/- 2.4 mM) > alpha(3) (1.6 +/- 0.5 mM) approximately alpha(1) (0.9 +/- 0.6 mM), and K(0.5) values for Na(+) antagonism of ouabain binding to all heterodimers were 9.5-13.8 mM. The molecular turnover for ATP hydrolysis by alpha(1)beta(1) (6,652 min(-1)) was about twice as high as that by alpha(3)beta(1) (3,145 min(-1)). These properties of the human heterodimers expressed in yeast are in good agreement with properties of the human Na(+)-K(+)-ATPase expressed in Xenopus oocytes (G Crambert, U Hasler, AT Beggah, C Yu, NN Modyanov, J-D Horisberger, L Lelievie, and K Geering. J Biol Chem 275: 1976-1986, 2000). In contrast to Na(+) pumps expressed in Xenopus oocytes, the alpha(2)beta(1) complex in yeast membranes was significantly less stable than alpha(1)beta(1) or alpha(3)beta(1), resulting in a lower functional expression level. The alpha(2)beta(1) complex was also more easily denatured by SDS than was the alpha(1)beta(1) or the alpha(3)beta(1) complex.

Adenosine Triphosphate↗
PubMed2001

RT-PCR detection of the Na,K-ATPase beta3-isoform in human heart.

The Na,K-ATPase is a heterodimer composed of an alpha-catalytic and a beta-glycoprotein subunit. At present, three different alpha-polypeptides (alpha1, alpha2, alpha3) and two distinct beta-isoforms (beta1 and beta2) have been detected in human heart. The aim of the present study was to determine whether or not the beta3-isoform of the Na,K-ATPase can be detected in human heart. Using the highly sensitive method of RT-PCR, we here show that human heart expresses the beta3-isoform of the Na,K-ATPase. Given the differences in pharmacological properties of the nine different Na,K-ATPase isoenzymes (containing all combinations of the subunit isoforms), the study of beta3-isoform regulation in human heart may be of interest in understanding the altered response of human myocardium to digitalis therapy during heart failure.

Animals↗
PubMed2001

Region specific regulation of sodium pump isoform and Na,Ca-exchanger expression in the failing human heart--right atrium vs left ventricle.

Na,K-ATPase (NKA, Na-pump), an alphabeta heteromer, is the receptor for cardiac glycosides (CG) which exert a positive inotropic effect by inhibiting enzyme activity, decreasing the driving force for Na,Ca-exchange (NCX) and increasing cellular content and release of Ca2+ during depolarization. Our previous study of regional distribution of NKA in non-failing human hearts demonstrated that Na-pump alpha2-, alpha3- and beta1-isoforms were 30-50% lower in right atrium (RA) compared with left ventricle (LV), resulting in overall lower NKA activity and CG binding site number and increased sensitivity to inotropic stimulation. In failing human heart LV Na-pump alpha1, alpha3 and beta1 proteins were reduced 30-40%, with no change in alpha2 or NCX; NKA activity and CG binding sites decreased 40%, and sensitivity to inotropic stimulation increased, all compared to LV from non-failing hearts. In this study we investigated the influence of region specific factors (e.g. hemodynamics) on the regulation of NKA isoform and NCX expression in heart failure by comparing the pattern of change in right atrial myocardium during heart failure with that previously determined for LV. In RA samples from failing hearts, alpha1-, alpha2- and beta1-isoform protein expression were decreased by 40, 50 and 25%, respectively, with no significant change in alpha3 or NCX levels relative to non-failing hearts (both n= 12). Thus, alphabeta1 decreases in both RA and LV during heart failure, while alpha2beta1 is reduced only in RA and alpha3beta1 only in LV. This indicates that there are not only regional differences in normal cardiac Na-pump isoform expression but also regional differences in the pattern of isoform expression as a function of failure that may have distinct functional consequences in the adaptive process of heart failure. The mechanisms underlying Na,K-ATPase regulation and effect of hemodynamics remain to be investigated.

Adult↗