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R H G Schwinger

Publications and source records attributed to R H G Schwinger.

10 recordsLinked to original sources
PubMed2006

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin-angiotensin system.

AIMS/HYPOTHESIS: The angiotensin II (type 1) (AT1) receptor mediates many biological effects of the renin-angiotensin system (RAS), leading to remodelling of cardiac tissue. The present study was designed to analyse changes in the function and expression of the AT1 receptor as principal effector of the RAS in myocardium from type 2 diabetic patients compared with non-diabetic myocardium as control. In addition, we determined the effect of treatment with ACE inhibitors or AT1 receptor blockers on expression levels of the receptor in diabetic patients. METHODS: Gene expression of the AT1 receptor was analysed by quantitative RT-PCR and protein expression was determined by immunoblot analysis in human right atrial myocardium. We investigated functional coupling of the receptors by measuring contractility in isolated trabeculae stimulated with increasing concentrations of angiotensin II. RESULTS: Diabetic myocardium showed a significant increase in protein expression (170 +/- 16% of control) and median mRNA expression (186% of control) of the AT1 receptor. The additional receptors were functionally coupled, resulting in a stronger inotropic response upon stimulation with angiotensin II (89 +/- 5.5% vs 29 +/- 1.6% in controls), whereas receptor affinity was similar in both groups. However, myocardium from diabetic patients treated with ACE inhibitors or AT1 receptor blockers showed no increase in AT1 receptor expression. CONCLUSIONS/INTERPRETATION: AT1 receptor expression in myocardium of type 2 diabetic patients is dynamic, depending on the level of glycaemic control and the activity of the RAS. These findings could at least in part explain the strong therapeutic benefit of RAS inhibition in diabetic patients.

Aged↗
PubMed2006

Beta3-adrenergic stimulation in the human heart: signal transduction, functional implications and therapeutic perspectives.

Next to beta1- and beta2-adrenoceptors, a third beta-adrenoceptor population is expressed in the human heart, the beta3-adrenoceptor. In mammalian ventricular myocytes, beta3-adrenergic stimulation leads to a decrease in contractility via a release of nitric oxide (NO). Recently, different molecular mechanisms of beta3-adrenergic activation of endothelial nitric oxide synthase (eNOS) have been uncovered in cardiac myocytes. In the non-failing and especially the failing heart, beta3-adrenergic stimulation may offer protection against excessive catecholaminergic beta1-adrenoceptor stimulation. In this context, the beta3-adrenoceptor is discussed as a novel target for the pharmacological therapy of heart failure.

Adrenergic beta-3 Receptor Agonists↗
PubMed2005

Overexpression of sorcin enhances cardiac contractility in vivo and in vitro.

Sorcin (SOR), an EF-hand Ca(2+)-binding protein, interacts with the sarcolemmal proteins Annexin VII and L-type Ca(2+)-channel and with the sarcoplasmic reticulum (SR) Ca(2+)-release channel (ryanodine-receptor, RYR), and has been implicated to influence the intracellular Ca(2+)-homeostasis. The present study aimed at investigating the effects of increased SOR expression on force development and relaxation in virus transfected rat hearts and isolated cardiomyocytes. We generated an adenovirus encoding the SOR coding DNA with a separate cassette for green fluorescent protein (GFP) both driven by the CMV-promoter to induce SOR-overexpression (Ad.SOR.GFP). As control served an adenovirus carrying an empty cassette with a separate cassette for GFP also driven by CMV-promoters (Ad.GFP). Cardiomyocytes of healthy male rats were isolated, transfected and cultured for 48 h with Ad.SOR.GFP as well as Ad.GFP as control. In addition, Ad.SOR.GFP was injected into coronary arteries via a catheter-based technique and rat hearts were transfected in vivo for 12 days. Echocardiography was performed to assess cardiac function at 7 and 12 days before the animals were sacrificed. A 1.7-fold increase of the SOR protein amount in cultured myocytes treated with Ad.SOR.GFP compared to Ad.GFP-transfected cells indicated a successful overexpression of SOR. Cell-contracting experiments using infected cardiomyocytes (transfection: 48 h; frequency: 0.5 Hz) exhibited a significantly higher peak force of contraction (FOC) in the SOR-overexpression group (n = 64) vs. control (n = 21) (6.8% +/- 0.2% vs. 4.3% +/- 0.1%). Beta-adrenergic stimulation with forskolin resulted in similar increases in FOC. Echocardiography of in vivo transfected rat hearts exhibited enhanced fractional shortening (65.9 +/- 5.5% vs. 79.3 +/- 2.5%) and decreased end-systolic diameters indicating enhanced cardiac contractility. Gross morphology was similar in both groups after 14 days of transfection. These results strengthen the notion that overexpression of SOR improves cardiac contractility independent of beta-adrenergic stimulation and may prove beneficial in the treatment of decreased cardiac output such as heart failure.

Adenoviridae↗
PubMed2004

Calcineurin independent development of myocardial hypertrophy in transgenic rats overexpressing the mouse renin gene, TGR(mREN2)27.

Myocardial hypertrophy is an independent risk factor for development of heart failure. The intracellular calcium homeostasis is altered in myocardial hypertrophy, and recent studies in animal models have confirmed an interaction between the Ca2+/calmodulin-dependent calcineurin signaling cascade and development of cardiac hypertrophy. There is evidence for the involvement of various pathways in development of hypertrophy. A transgenic rat model overexpressing the mouse renin gene, TGR(mREN2)27 has been shown to progress profound cardiac hypertrophy, possibly due to a monogenetic disorder. However, the exact mode of action is not known. To study a possible involvement of calcineurin and its downstream pathway in development of cardiac hypertrophy in this transgenic rat model we measured the protein expression of marker proteins of the calcineurin cascade (calcineurin, NFAT-3, GATA-4) and calcineurin phosphatase activity and GATA-4 DNA binding in TGR ( n=10) compared to age-matched Sprague-Dawley rats ( n=10). In our study there was no significant difference in calcineurin activity between the transgenic hearts and the hearts of Sprague-Dawley rats. Furthermore, we found neither an increase in protein expression of calcineurin B nor a rise in nuclear translocated NFAT-3 DU. Interestingly, the protein expression of GATA-4 and its DNA binding activity were significantly higher in hypertrophied myocardium than in control hearts. In transgenic rats overexpressing the mouse renin gene and thereby developing pronounced cardiac hypertrophy [TGR(mREN2)27] we thus found no activation of calcineurin or its downstream pathway. However, the expression of the transcriptional factor GATA-4 and its DNA binding activity were significantly increased in hearts of transgenic rats. Thus GATA-4 seems to be a marker of hypertrophy independently of calcineurin activation, possibly activated by various pathways.

Animals↗
PubMed2004

Interference by cellular phones with permanent implanted pacemakers: an update.

AIMS: The aim of this study was to test pacemakers with feedthru filters for interference with a digital cellular telephone. METHODS: The study comprised 100 patients having their first pacemaker implantation between January 2001 and May 2003. A GSM-standard cellular phone was tested in the standby, dialing and operating mode against 23 single-chamber and 77 dual-chamber pacemakers. Continuous surface electrocardiograms, intracardiac electrograms, and marker channels were recorded when calls were made by a land phone to the cellular phone. RESULTS: In 2 patients we observed pacing inhibition with the cellular phone positioned directly above the pacemaker pocket. The unipolar and bipolar ventricular sensitivity setting was 0.25 mV in one dual-chamber pacemaker, and when we changed the sensitivity to 0.50 mV and higher no interference could be detected. The second inhibition occurred in a single-chamber pacemaker with unipolar and bipolar ventricular sensitivity setting of 0.5 mV, where a sensitivity change to 1.0 mV eliminated the interference. CONCLUSION: Anticipating a correct setting of ventricular sensitivity, currently available pacemakers equipped with feedthru filters do not show any interference with cellular phones. Since interference was only observed with sensitivity settings below 0.50 mV, we recommend that permanent programming of ventricular sensitivity should be set at 2.0 mV and higher.

Adolescent↗
PubMed2004

The effect of preoperative antiplatelet therapy in coronary artery surgery: blood transfusion requirements for patients on cardiopulmonary bypass.

INTRODUCTION: Bleeding after heart operations remains a common complication and contributes to morbidity and death. Recent studies have suggested that antiplatelet therapy (APT) may not increase homologous blood requirements in coronary bypass surgery. The purpose of this study was to examine the influence of APT therapy on haemorrhage and transfusion requirements in patients undergoing coronary artery bypass (CABG) on cardiopulmonary bypass (CPB). MATERIALS AND METHODS: Records from 290 consecutive patients who underwent CABG with CPB were retrospectively reviewed, including 145 patients who received APT within 5 days prior to surgery and 145 control patients (CON). Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge. RESULTS: Both groups were well matched with respect to demographic and intra-operative data. There was significantly (p < 0.0005) more mediastinal tube drainage at 24 h in the APT group (1123 mL +/- 537 mL) compared to CON patients (874 mL +/- 351 mL). In addition, the APT group received significantly more units of blood (APT: 2.6 +/- 2.5 vs CON: 1.6 +/- 1.8; p < 0.0005), platelet units (APT: 1.2 +/- 1.8 vs CON: 0.2 +/- 0.8; p < 0.0005), and fresh frozen plasma units (APT: 2.0 +/- 2.2 vs CON: 1.3 +/- 2.0; p = 0.01). CONCLUSION: This study suggests consideration should be given to delaying elective CABG for patients who have received APT treatment until APT is discontinued for at least 5 days.

Blood Loss, Surgical↗
PubMed2004

[Beta-adrenoceptor antagonists in the treatment of chronic heart failure].

Beta-Adrenoceptor antagonists in the treatment of chronic heart failure The incidence of chronic heart failure is high in the developed countries (1-4/1000 per year). Treatment of chronic heart failure is a therapeutic challenge. A great improvement in mortality and morbidity of heart failure patients was achieved by the introduction of beta-adrenoceptor blockers in the treatment of chronic heart failure. However only 39% of heart failure patients are treated with a beta-adrenoceptor blocker in Europe. This review outlines pathophysiology of the beta-adrenergic system during human heart failure and its alterations induced by beta-adrenoceptor blockade. Based on the results of large clinical trials, experimental-pharmacological properties of beta-adrenoceptor blockers as well as the main aspects of its clinical use are discussed.

Adrenergic beta-Antagonists↗
PubMed2003

The preferential beta3-adrenoceptor agonist BRL 37344 increases force via beta1-/beta2-adrenoceptors and induces endothelial nitric oxide synthase via beta3-adrenoceptors in human atrial myocardium.

1 The present study investigated the effects of the preferential beta(3)-AR agonist BRL 37344 (BRL) on force of contraction (FOC), Ca(2+)-transient and eNOS-activity in human right atrial myocardium. 2 BRL concentration-dependently caused an increase in FOC that was paralleled by an increase in Ca(2+)-transient and a shortening of time to half peak relaxation (T0.5T). These effects were abolished in the presence of propranolol (0.3 micro M). 3 BRL acted as a competitive antagonist towards isoprenaline and in binding experiments it was shown to have a distinct affinity towards beta(1/2)-AR. 4 In immunohistochemical experiments BRL (10 micro M) increased detection of activated eNOS. This effect remained constant in the presence of propranolol (0.3 micro M). 5 BRL increased directly detected NO in DAF-staining experiments. This increase was significantly smaller in the presence of the NO-inhibitor L-NAME. 6 The inotropic effects of BRL were not changed in the presence of L-NMA. 7 These results suggest that the inotropic effects of BRL in human atrium are mediated via beta(1/2)-AR, whereas the increase of atrial eNOS-activity is due to beta(3)- adrenergic stimulation. This increase in eNOS-activity did not influence atrial myocardial contractility. In conclusion, this study shows that beta(3)-adrenergic stimulation is present in human atrium, but may not be functionally as significant as in the left ventricle.

Adrenergic beta-Agonists↗
PubMed2002

Effects of the Ca2+ sensitizers EMD 57033 and CGP 48506 on myocardial contractility and Ca2+ transients in human ventricular and atrial myocardium.

Ca2+ sensitizers like EMD 57033 (EMD) and CGP 48506 (CGP) may be advantageous for the treatment of human heart failure, as they increase force of contraction without increasing the intracellular Ca2+ transients or energy consumption. However, whether or not Ca2+ sensitizers differ in their mode of action in human myocardium is not fully understood. The present study investigates the influence of EMD and CGP on force of contraction (FOC) and the intracellular Ca2+ transient (fura-2 ratio method) in left ventricular papillary muscle strips from left ventricular failing human myocardium (DCM, n = 28) as well as in right atrial trabeculae (RA, n = 21) obtained from patients undergoing cardiac bypass surgery. In isolated trabeculae of DCM, FOC was more efficacious and potently increased after application of EMD (EC50 EMD: 4.7 +/- 1.0 mumol/l, max. PIE EMD: + 12.0 +/- 2.0 mN/mm2) than CGP (EC50: 16.9 +/- 7.6 mumol/l, max. PIE: +6.4 +/- 2.8 mN/mm2). Similar results were obtained in RA. Application of carbachol (100 mumol/l) had no effect on the positive inotropic effect of EMD or CGP. Both Ca2+ sensitizers significantly increased time to half peak relaxation as well as diastolic tension in DCM. EMD (10 mumol/l) and CGP (30 mumol/l) did not affect the Ca2+ transients in RA. The Ca2+ sensitizers EMD and CGP increase cAMP and Ca2+ independently from the force of contraction in the human myocardium. However, their therapeutic use in human heart failure may be limited as they impair relaxation.

Azocines↗