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Biomedical subjects

R Dietz

Publications and source records attributed to R Dietz.

At least 109 records · Page 6Linked to original sources

Acute hemodynamic and renal effects of adrenomedullin in rats with aortocaval shunt.

Heart failure is characterized by increased vascular resistance and water retention. Adrenomedullin is a peptide hormone with vasodilating and diuretic properties whose efficacy in heart failure has not been well established. We used an aortocaval shunt model of moderate heart failure in rats and infused increasing doses of adrenomedullin, both as bolus injections and 20-min infusions. In controls, a clear dose-dependent 4.8+/-1.0 to 13.6+/-2.3 mm Hg decrease in arterial blood pressure was observed after injection of 1 microg to 30 microg of adrenomedullin. In rats with aortocaval shunt, the hypotensive responses were significantly diminished. The urine flow rate, which was diminished at baseline in rats with aortocaval shunt, was increased and normalized by adrenomedullin administration. The glomerular filtration rate increased after infusion of adrenomedullin (0.5 microg/kg min(-1)) from 2.37+/-0.25 to 3.47+/-0.43 ml/min (P<0.01) in controls and from 1.79+/-0.33 to 2.58+/-0.49 (P<0.05) in rats with aortocaval shunt. Similarly, renal blood flow was significantly increased by adrenomedullin in both groups. Our results indicate a beneficial effect of adrenomedullin on renal function in rats with aortocaval shunt. These data suggest that adrenomedullin might be of potential therapeutic value in heart failure, without inordinately decreasing blood pressure.

Adrenomedullin↗

Percutaneous treatment of pseudoaneurysms and arteriovenous fistulas after invasive vascular procedures.

Development of femoral artery pseudoaneurysms and arteriovenous fistulas represents a continuing problem after vascular diagnostic and interventional procedures. For most patients, ultrasound-guided compression is an effective method of treating such complications. However, in patients requiring a continuous anticoagulant regimen, in those with large arteriovenous fistulas or in patients suffering from painful groin hematomas, compression repair is less successful. We therefore assessed the feasibility, efficacy, and long-term results of interventional percutaneous treatment of these complications. In a 40-month period, we treated 53 consecutive patients with 30 pseudoaneurysms, 21 arteriovenous fistulas, and 2 combined lesions. The intervention was successful in 47 patients: 32 lesions were treated by implantation of covered stents, 14 by embolization techniques, and 1 by a combined procedure, surgical repair being necessary only in 6 patients. After a clinical and ultrasonic follow-up of 301 +/- 280 days, we noticed four late stent occlusions, especially in patients with poor peripheral runoff. Lesions with a distinct connection channel to the vessel lumen should be treated by coil embolization. In lesions originating from the femoral bifurcation with a broad base, surgical repair is necessary. Stenting of the superficial femoral artery with poor runoff should be avoided. Our results suggests that percutaneous closure of false aneurysms and arteriovenous fistulas after invasive procedures with unsuccessful ultrasonic compression repair is an attractive alternative to surgical treatment.

Aged↗

[Drug therapy for prognostic improvement after acute myocardial infarct].

This review article summarizes the long-term standard therapy for patients with myocardial infarction. The chronic therapy is able to significantly improve quality of life and survival of affected patients. Previous studies showed that in most western countries, the established standard therapy is not given to all patients who would benefit from chronic treatment. The essential parts of today's myocardial infarction treatment consists of effective beta-blockade, inhibition of the angiotensin-conversion enzyme, inhibition of platelet aggregation and lipid lowering agents. This article reviews the clinical benefits which may be expected from each of these therapeutic approaches. Newer, but not yet proven strategies, like blockade of the angiotensin receptor subtype 1 and treatment with antioxidative agents will be discussed.

Adrenergic beta-Antagonists↗

A novel isoform of the smooth muscle cell differentiation marker smoothelin.

Studies on smooth muscle cell differentiation and those on vascular development in mouse and humans have long been hampered by the lack of suitable markers. Here we describe a novel, large isoform of smoothelin, a structural protein of differentiated, contractile smooth muscle cells. The protein, which is highly conserved in mouse and humans, shows homology with other cytoskeleton-associated smooth muscle cell proteins and contains an actinin-type actin-binding domain. Northern blot analysis from various mouse organs identified short and long smoothelin mRNA forms, which exhibit distinct tissue expression patterns. The short form is highly expressed in visceral muscle tissues such as intestine and stomach and is not detectable in brain, while the long mRNA form is expressed in all vascularized organs. These results may provide new tools and approaches to study both smooth muscle cell differentiation and proliferative vascular disease.

Actinin↗

Dose-dependent stereoselective activation of the trigeminal sensory system by nicotine in man.

RATIONALE: Nicotine applied to the nasal cavity can evoke 'odorous' sensations in the concentration range near the detection threshold by the activation of the olfactory sensory system and at higher concentrations 'burning' and 'stinging' sensations by the dose-dependent recruitment of C- and Adelta-fibers of the trigeminal sensory system. Neuronal nicotinic acetylcholine receptor (nAchR) subunits are expressed in trigeminal primary afferents and could constitute the receptors involved in nicotine perception. OBJECTIVE: In the present study, we dose-dependently investigated the stereoselective effects of R(+)- and S(-)-nicotine on the trigeminal and olfactory sensory system in man. METHODS: Trigeminal detection thresholds for the 'burning' and 'stinging' sensations and the olfactory detection threshold for the 'odorous' sensation were determined. In order to quantify trigeminal activation, we recorded summated electrical responses from the respiratory nasal mucosa during stimulation with R(+)-and S(-)-nicotine vapor (40, 80, 120, 160 ng/ml; stimulus duration: 250 ms). In addition, subjects rated the intensity of 'odorous', 'burning' and 'stinging' sensations. For chemical stimulation with nicotine enantiomers, a vapor-dilution olfactometer (constant flow rate: 140 ml/s, humidity: 80%, temperature: 37 degrees C, stimulus duration 250 ms) was employed. RESULTS: We found significant stereoselective differences for the trigeminal but not for the olfactory system, i.e. higher summated responses, higher trigeminal intensity estimates, and lower trigeminal detection thresholds for S(-)- compared to R(+)-nicotine. CONCLUSION: Our results clearly demonstrate the different stereoselective activation of the trigeminal sensory system by R(+)-and S(-)-nicotine, indicating the presence of specific stereoselective receptors on trigeminal nociceptive Adelta- and C-fibers.

Adult↗

[Left ventricular remodeling: pathophysiological mechanisms and therapeutic recommendations].

Hospital mortality from acute myocardial infarction has decreased in the last two decades. Left ventricular dysfunction therefore have been mainly due to ischemia. After extensive myocardial infarction, there are processes of adaptation (remodeling) which result in altered geometry of the left ventricle. The effects of this on neurohormonal systems (organ regulation), on the changed ratio of myocyte mass and collagen content owing to reactive and reparative fibrosis (organ texture) and on the molecular and cellular mechanisms (organ structure) are of crucial importance. Depending on the structural changes, the myocardial contractility decreases. This is associated with an activation of the circulating renin-angiotensin-aldosterone system (RAAS). The fundamental knowledge available has led to the therapeutic use of ACE inhibitors in the post-infarct period. This treatment enabled a sustained reduction of mortality in several large-scale randomized studies. The effect of early administration in patients with clinical signs of heart failure and/or left ventricular dysfunction was very much greater compared to unselected controls. Only 17 and 13 patients had to be treated after selection in order to save one life in the AIRE and TREACE Study respectively (NNT: number needed to treat), whereas e.g. in the ISIS-4 study 200 unselected patients had to be treated. In clinical practice, however, this life-saving therapy is only used in every second patient requiring treatment. With consideration of an individual form of treatment (anterior infarction, large infarct area, reinfarction, clinical signs of heart failure as well as arterial hypertension and diabetes mellitus), a greater acceptance of evidence-based guidelines is thus desirable. Treatment with a high dose may be expected to be of additional benefit.

Angiotensin-Converting Enzyme Inhibitors↗

Angiotensin inhibition and atrial natriuretic peptide release after acute volume expansion in rats with aortocaval shunt.

OBJECTIVE: In heart failure atrial natriuretic peptide (ANP) release in response to volume expansion is impaired while the renin-angiotensin system is activated. This study was designed to test the hypothesis that ANP release in heart failure is dependent on an activated angiotensin system. METHODS: We studied the ANP and renin-angiotensin systems in a rat model of shunt-induced high-output heart failure, in which we rapidly increased circulating fluid volume with a 5 ml, hyperoncotic infusion, and evaluated the effects of acute inhibition of the angiotensin converting enzyme as well as of the blockade of the angiotensin II type 1 receptors on the ANP release and on renal excretory function. RESULTS: ANP and angiotensin II plasma concentrations prior to volume expansion were elevated (p < 0.05) in rats with aortocaval shunt compared to controls. The diuretic response to acute volume expansion (18.5 +/- 1.5 vs. 48.2 +/- 2.4 microliters/min, p < 0.001) was markedly blunted. ANP release was attenuated in rats with aortocaval shunt, as was the increase of its second messenger cGMP in plasma and urine. The blunted increase in ANP plasma levels was not due to depleted cardiac stores as cardiac ANP content, as well as ANP synthesis, were increased (p < 0.05). Acute inhibition of the angiotensin converting enzyme as well as blockade of the angiotensin II type 1 receptors restored ANP release in response to volume expansion (p < 0.01). Moreover, acute inhibition of the renin-angiotensin system completely normalized the diuretic response. CONCLUSIONS: Our data suggest that the ANP system is impaired in rats with aortocaval shunt. The activation of the angiotensin system contributes to the impairment of the ANP system. Acute inhibition of the angiotensin II system significantly improved the ability of the ANP system to respond to acute volume expansion. Our findings indicate a hitherto fore unappreciated interaction between both systems and suggest additional mechanisms for the beneficial effects of angiotensin converting enzyme inhibition or angiotensin II type 1 receptor antagonists in heart failure.

Angiotensin II↗

Regulation of cardiac adrenomedullin-mRNA in different stages of experimental heart failure.

Adrenomedullin (AM) is a peptide hormone with vasodilating and natriuretic properties. AM plasma concentrations are elevated in heart failure. Whether cardiac AM-mRNA synthesis is increased in heart failure is not known. We measured AM-mRNA/GAPDH-mRNA in all four heart chambers in compensated and overt heart failure in rats with two different sizes of aortocaval shunt. Left and right atrial AM-mRNA expressions were unchanged in both heart failure models. Similarly, left and right ventricular AM-mRNA expressions were unchanged in compensated heart failure. In overt heart failure, however, the AM-mRNA expression was significantly increased in the left ventricle (145+/-20 vs. 100+/-3% of control, p<0.05). The right ventricular AM-mRNA expression was significantly increased only in a subgroup of animals with pulmonary congestion (lung weight >2.0 g, 141+/-16 vs. 100+/-11% of control, p<0.05). Ventricular AM concentrations were elevated in both ventricles in overt heart failure. AM plasma concentrations were significantly higher in the subgroup with pulmonary congestion than in rats with compensated heart failure (496+/-95 vs. 143+/-7 pmol/l, p<0.01). These data indicate that ventricular AM-mRNA expression and AM concentrations were upregulated only in advanced stages of heart failure. However, the exact contribution of cardiac AM synthesis to the increased AM plasma levels remains to be established.

Adrenomedullin↗

Effect of rotational speed on nickel-titanium file distortion.

Separation of instruments while performing root canals is something that has plagued all practitioners. The purpose of this study was to evaluate the effect of rotational speed on nickel-titanium file distortion and separation. Forty extracted human molars were instrumented with Profile (Dentsply Tulsa Dental Products, Tulsa, OK) ISO .04 rotary nickel-titanium instruments at 166.67 or 333.33 rpm. The instruments were evaluated after instrumentation for separation and/or distortion. The results of this study were statistically significant and indicate that file distortion and/or separation is four times as likely to occur at 333.33 rpm vs. 166.67 rpm.

Dental High-Speed Technique↗

Investigation of a family with autosomal dominant dilated cardiomyopathy defines a novel locus on chromosome 2q14-q22.

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and the most frequent indication for heart transplantation in young patients. Probably >25% of DCM cases are of familial etiology. We report here genetic localization in a three-generation German family with 12 affected individuals with autosomal dominant familial DCM characterized by ventricular dilatation, impaired systolic function, and conduction disease. After exclusion of known DCM loci, we performed a whole-genome screen and detected linkage of DCM to chromosome 2q14-q22. Investigation of only affected individuals defines a 24-cM interval between markers D2S2224 and D2S2324; when unaffected individuals are also included, the critical region decreases to 11 cM between markers D2S2224 and D2S112, with a peak LOD score of 3.73 at recombination fraction 0 at D2S2339. The identification of an additional locus for familial autosomal dominant DCM underlines the genetic heterogeneity and may assist in the elucidation of the causes of this disease.

Adolescent↗

Quantification of low abundance natriuretic peptide receptor mRNA in rat tissues.

Natriuretic peptides are important regulators of vascular resistance and volume and electrolyte homeostasis. The quantification of natriuretic peptide receptor (NPR) mRNA is important for the understanding of the regulation of this humoral system, but is difficult due to low expression of the NPR mRNA. We report here on the evaluation of a polymerase chain reaction (PCR)-aided transcript titration assay for quantification of all three NPR subtypes (NPR-A, NPR-B, and NPR-C) mRNA. A multispecific internal standard RNA with parts of NPR-A, NPR-B, NPR-C and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) nucleotide sequences was constructed and reverse transcription of standard and sample RNA (400 ng) was performed in parallel for all three NPRs and GAPDH. The specific PCR yielded differently sized products, which were quantified by high performance liquid chromatography (HPLC). The determination of specific mRNA concentrations was not influenced by cDNA input and did not depend on the PCR cycle number. Linearity between sample RNA input and mRNA concentration was demonstrated. Application of the evaluated method showed that the NPR-A mRNA expression was the most abundant of the three natriuretic peptide receptor mRNAs in rat lungs, glomeruli and left ventricles, followed by the NPR-C mRNA and the NPR-B mRNA expression. Thus, the described method allows the reliable quantification of the specific mRNA expression of all three NPRs with small amounts of RNA. The presented method might foster future research on the regulation of this humoral system in cardiovascular and kidney diseases.

Animals↗

Renal function in high-output heart failure in rats: role of endogenous natriuretic peptides.

The physiologic and pathophysiologic importance of natriuretic peptides (NP) has been imperfectly defined. The diminished renal responses to exogenous atrial NP in heart failure have led to the perception that the endogenous NP system might be less effective and thus contribute to renal sodium retention in heart failure. This study tests the hypothesis that in experimental heart failure, the renal responses to an acute volume load are still dependent on the NP system. The specific antagonist HS-142-1 was used to block the effects of NP in a model of high-output heart failure induced by an aortocaval shunt. Plasma cGMP levels and renal cGMP excretion were significantly lower in shunted and sham-operated rats receiving HS-142-1, compared with vehicle-treated controls, indicating effective blockade of guanylate cyclase-coupled receptors. Baseline sodium excretion and urine flow rate were lower in HS-142-1-treated sham-operated rats (15.2+/-1.1 microl/min versus 27.5+/-3.1 microl/min with vehicle, P < 0.001) and in HS-142-1-treated shunted rats (8.1+/-1.3 microl/min versus 19.9+/-2.3 microl/min with vehicle, P < 0.001). After an acute volume load, the diuretic and natriuretic responses were attenuated by HS-142-1 in control and shunted rats. The renal responses were reduced by HS-142-1 to a significantly greater extent in shunted rats than in control rats. HS-142-1 did not induce any significant systemic hemodynamic changes in either group, nor did it alter renal blood flow. However, the GFR in HS-142-1-treated shunted rats was lower than that in vehicle-treated shunted rats, both at baseline (0.6+/-0.3 ml/min versus 2.1+/-0.4 ml/min with vehicle, P < 0.05) and after an acute volume load (1.2+/-0.4 ml/min versus 2.6+/-0.4 ml/min with vehicle, P = 0.01), whereas no such effect was observed in control rats. These data indicate that the maintenance of basal renal function and the responses to acute volume loading are dependent on the NP system. The NP seem to be of particular importance for the maintenance of GFR in this model of experimental heart failure. These observations provide new insights into the importance of the renal NP system in heart failure.

Analysis of Variance↗

The frequency of occurrence of anti-cardiac receptor autoantibodies and their correlation with clinical manifestation in patients with hypertrophic cardiomyopathy.

The purpose of this study was to investigate the frequency of occurrence of autoantibodies against G-protein coupled cardiovascular receptors and their relation to the clinical manifestation of hypertrophic cardiomyopathy (HCM). Autoantibodies against beta1-receptors, Muscarin-2-receptors, Angiotensin-II-receptor subtype 1 and alpha1-receptors were determined with ELISA in 52 patients with HCM (37 male, 15 female, mean age 55 +/- 15 years) and 40 healthy, age and sex matched controls. The clinical characterization of the HCM-patients included ECG, 24-h Holter, and echocardiography. The results showed that there is no significant difference in the frequency of a single autoantibody between HCM-patients and controls. However, if the number of patients who have autoantibodies against beta1-receptors and/or Muscarin-2-receptors were counted together, there are significantly more autoantibodies in HCM compared to controls (11 vs. 2, p = 0.035). Analysis of clinical data from this pooled group of patients showed that in patients with autoantibodies, heart rate variability (HRV), ultra low frequency (ULF) and very low frequency (VLF) were decreased (HRV by 20%, ULF by 50%, and VLF by 46%, p < 0.008) whereas the QTc-interval was increased by 8% (p < 0.02 each). The ratio of septal to posterior wall thickness was increased by 23% (p = 0.05), and the preejection period was prolonged by 46% in patients with autoantibodies (p < 0.001). These results suggest that the existence of these autoantibodies could be associated with an advanced stage or a severe manifestation of HCM.

Adult↗

Safety of implantable coronary stents during 1H-magnetic resonance imaging at 1.0 and 1.5 T.

The safety of most available implantable intracoronary stents during magnetic resonance imaging (MRI) has not been sufficiently tested. Minor, but possibly clinically significant, increases in temperature have not been excluded. We measured temperature changes of 14 different stents clinically in use or currently tested for release on the world market. Stents were examined in 1.0- and 1.5-T MR scanners with multiple sequences used in routine cardiac and thoracic MRI examinations ("clinical worst case") and after implantation of the stents into the coronary arteries of excised pig hearts (1.5-T scanner only). We used a highly sensitive infrared camera with a thermal resolution of 10 mK and did not see significant heating of any stent during the examinations. We conclude that MRI is safe in patients with the currently available intracoronary stents.

Animals↗

Is intraoperative electrostimulation of erectile nerves possible?

PURPOSE: We improved intraoperative conditions to achieve better corpora cavernosal response to stimulation of the erectile nerves. MATERIALS AND METHODS: A total of 18 men undergoing nerve sparing retropubic prostatectomy were evaluated with intraoperative stimulation for identification of the erectile nerves. Intracavernosal pressure was measured directly or via electromyography of the corpora cavernosa. Different kinds of anesthesia were used with or without urapidil. RESULTS: Intracavernosal pressure was recorded in all patients. Use of isoflurane based anesthesia blocked change, and total intravenous anesthesia with propofol resulted in a measurable change in intracavernosal pressure during electrostimulation. However, local urapidil, a potent alpha-blocking agent, doubled or tripled intracavernosal pressure. Electromyography of the corpora cavernosa demonstrated no measurable change. CONCLUSIONS: Intraoperative electrostimulation of erectile nerves requires special anesthesia as well as local blocking of alpha-receptors. The functional anatomy of the erectile nerves is variable.

Aged↗

Ventricular remodeling after acute myocardial infarction.

The term ventricular remodeling has been coined to describe the geometrical changes in size and shape of the left ventricle occurring after large myocardial infarcts. We do not exactly know what initiates this process. Slipping of myofilaments following destruction of connective tissue--probably due to metalloproteinase activation--could be the initial event. As a consequence, wall stress is increased triggering deleterious adaptation processes, such as: - intracardiac angiotensin II generation; - cardiac endothelin formation and release; - pro-apoptotic signals for cardiomyocytes; - hypertrophic signals for fibroblasts and cardiomyocytes. This cascade of events is not only observed in the process of remodeling following myocardial infarction but is also operating during the progression of heart failure. Therapeutic principles therefore are similar in both conditions: - reduction of wall stress (pharmacological or mechanical unloading of the heart); - blockade of angiotensin II generation or of AT1-receptors (ACE-inhibitors or AT1 antagonists); - blockade of endothelin receptors (ET(A)-blockers); - blockade of adrenergic receptors (preferably beta1-adrenergic receptor blockers). Better understanding of the molecular mechanisms of the remodeling process already has fueled the search for new therapeutic interventions (such as endothelin receptor blockers, aldosterone antagonists and growth hormone application). Continuous research in this field may be especially rewarding if we will succeed in identifying the very first step in the cascade.

Animals↗