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Biomedical subjects

M Kelm

Publications and source records attributed to M Kelm.

At least 19 recordsLinked to original sources
PubMed2005

Recent advances in the understanding of the role of nitric oxide in cardiovascular homeostasis.

Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO) generation. To date, 3 distinct NOS isoforms have been identified: neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3). Biochemically, NOS consists of a flavin-containing reductase domain, a heme-containing oxygenase domain, and regulatory sites. NOS catalyse an overall 5-electron oxidation of one Nomega-atom of the guanidino group of L-arginine to form NO and L-citrulline. NO exerts a plethora of biological effects in the cardiovascular system. The basal formation of NO in mitochondria by a mitochondrial NOS seems to be one of the main regulators of cellular respiration, mitochondrial transmembrane potential, and transmembrane proton gradient. This review focuses on recent advances in the understanding of the role of enzyme and enzyme-independent NO formation, regulation of NO bioactivity, new aspects of NO on cardiac function and morphology, and the clinical impact and perspectives of these recent advances in our knowledge on NO-related pathways.

Animals↗
PubMed2005

[Acute coronary syndrome: unstable angina and myocardial infarction].

The acute coronary syndrome comprises unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction. A successful and stable revascularisation of the infarct related vessel, and the prevention of the loss of myocardium are the main therapeutic targets, as cardiovascular mortality and long term quality of life are essentially determined by left ventricular function. The clinical diagnosis comprises clinical symptoms, ECG-changes, and cardiac troponins. Early percutaneous coronary intervention (PCI) has become the most common method of coronary revascularisation. If PCI is not available, systemic thrombolysis is an alternative after exclusion of contraindications. Parenteral anticoagulation with intravenous or subcutaneous heparines, antithrombotic therapy and HMG-CoA reductase inhibitors are the common secondary drug therapy. Moreover, to prevent left ventricular remodelling ACE-inhibitors, angiotension 2-receptor antagonists, and beta-blocker are indicated.

Acute Disease↗
PubMed2005

Sirolimus-eluting stent treatment for isolated proximal left anterior descending artery stenoses. Results from the prospective multi-center German Cypher Registry.

BACKGROUND: Stenting of isolated proximal LAD stenoses is still a controversial issue since it is associated with higher target vessel revascularization (TVR) rate than both bypass surgery using the internal mammary artery, and stenting of other coronary artery territories. The sirolimus- eluting stent (SES) has been reported to significantly reduce restenosis rates in de novo coronary lesions. Therefore, we compared patients from the German Cypher Registry treated with SES for isolated proximal LAD lesions with those stented for isolated lesions in the proximal LCX or RCA. METHODS: A total of 349 patients treated with SES were analyzed. 249 patients were treated for proximal LAD stenosis, and 100 for proximal LCX/RCA stenoses. The combined clinical endpoint was MACCE (death of any cause, non-fatal MI and non-fatal stroke) and TVR at 6 months. RESULTS: In-hospital events (death, MI and TVR) did not differ significantly between both groups (3.2% for the LAD group vs 2.0% for the LCX/RCA-group, p=0.73). The combined end point of death of any cause, non-fatal MI and non-fatal stroke at six months was 2.6% in the LAD group, and 2.2% in the LCX/RCA group (p=1.0). TVR occurred in 4.8% of the LAD group and in 6.5% of the LCX/RCA group at six months (p=0.58). The percentage of patients free from angina at daily activities was 80.6% in the LAD group, and 77.4% in the LCX/ RCA group (p=0.52). CONCLUSION: SES once implanted into isolated proximal LAD stenoses appears as effective as reported in other vessel territories. Accordingly, stenting of the proximal LAD using SES might prove a suitable alternative to surgery.

Activities of Daily Living↗
PubMed2004

"Real life" use of sirolimus-eluting coronary stents in Germany. Results from the prospective multi-centre German Cypher Registry.

BACKGROUND: Drugeluting stents (DES) are currently judged to be a "break-through" technology for the prevention of restenosis after percutaneous coronary interventions (PCI). However, experience is limited to randomised controlled clinical trials (RCT) in selected lesions and the currently available DES are more expensive compared to conventional "bare" stents. Therefore, actual clinical practice may be very different to RCT. METHODS: We analysed the data of the German Cypher trade mark Registry, a nationwide registry which was initiated in parallel to the launch of the first DES, the Cypher trade mark sirolimus-eluting coronary stent, in April 2002. RESULTS: From April 2002 until March 2003, 1638 procedures at 88 hospitals were included in the German Cypher trade mark Registry. The mean inclusion rate per centre and month remained low (<3 procedures/month and participating hospital) during the whole inclusion period. Most patients presented with stable angina pectoris (45.8%); however, 6.4% of patients were treated for a non-ST elevation myocardial infarction, 10.3% of patients for ST elevation myocardial infarction and 1.7% in cardiogenic shock. In patients without ST elevation myocardial infarction, a de novo stenosis was treated in 68.4% of cases, a restenosis in 4.1%, and an in-stent restenosis in 25.5% of cases. Chronic total occlusions were treated in 6.1% of patients. Predilatation was performed in 68.3% of patients and 1.05 +/- 0.35 Cypher trade mark stents were implanted per patient with a median (quartiles) stent length of 18 (13-21) mm. PCI-related death occurred in 0.1% of patients and a Q-wave myocardial infarction in 1.1%. Urgent re-PCI before hospital discharge was performed in 1.3% and urgent bypass surgery in 0.1% of cases. CONCLUSIONS: The use of the sirolimus-eluting coronary stents in this "real life" registry was found to be safe concerning acute complications. In about one half of the registry patients, the DES was implanted in lesions that were excluded from RCTs.

Blood Vessel Prosthesis↗
PubMed2003

[Hypertensive heart disease and microangiopathy].

Cardiac alterations in patients with arterial hypertension comprise the manifestation of stenosis in epicardial arteries, disease of coronary resistive vessels, prothrombotic changes and endothelial dysfunction, pronounced perivascular and interstitial fibrosis, left ventricular hypertrophy, dilatation of the left atrium, increased sympathetic drive and degeneration of aortic valve. These alterations leads to the major clinical manifestations of hypertensive heart disease, that are symptoms of reduced coronary conductance, left ventricular hypertrophy, diastolic and systolic dysfunction with or without left ventricular enlargement and arrhythmia. Different non-invasive and invase procedures are available for screening and follow up of patients with hypertensive heart disease. The primary therapeutic target is, apart from lowering blood pressure, to reverse cardiac manifestations of arterial hypertension using specific therapeutic algorithms.

Antihypertensive Agents↗
PubMed2002

[Duplex ultrasound determination of shunt volume in iatrogenic arteriovenous fistulas after heart catheterization].

AIM: To determine the shunt volume of iatrogenic arteriovenous fistula (AVF) following arterial puncture of the groin and to evaluate its impact on natural history and clinical outcome. METHOD: Over a period of 12 months, 22 patients (p) with a newly acquired AVF were followed up. The arteriovenous shunt volume was determined by means of colored duplex- and doppler sonography immediately after diagnosis of AVF. RESULTS: Spontaneous closure of AVF was seen in 10 p (46%) during follow-up examination, whereas 12 p (54%) showed a persistence of their AVF. The median (I50) shunt volume of closed AVF was 310 (250-350) ml/min and 350 (160-510) ml/min for persistent fistulae (p = ns). A shunt volume of > or = 400 ml/min was determined as a significant (p < or = 0.05) cut-off point for prolonged persistence of AVF. CONCLUSION: Because spontaneous closure of AVF was 46% in the course of the first year, conservative management with regular duplex control seems to be justified at least for this duration. Patients with a shunt volume of > or = 400 ml/min have an increased risk of prolonged AVF persistence and therefore should be included in long-term follow-up with special attention to development of hemodynamic relevance.

Arteriovenous Fistula↗
PubMed2001

[Lipoid pneumonia following attempted suicide by intravenous injection of lamp oil].

BACKGROUND: Pneumonic complications after intoxication with mineral oils have been described before in the contents of accidental aspiration and oral ingestion. However, intoxication following an intravenous injection leading to a lipoid pneumonia after an attempted suicide is a rare finding. CASE REPORT: A case report is presented of an attempted suicide by intravenously self-injection of 20 ml lamp oil (liquid paraffin). Immediately after injection the patient suffered from dry coughing which changed in the course of the next hours into a productive cough with white thick mucous sputum accompanied by hemoptysis. Additionally, he developed a mild disseminated intravascular coagulation with a fall of thrombocytes, an INR of 1.6 and a rise of D-dimeres. Under a therapy with hydrocortisone, ascorbic acid, ambroxol, acetylcysteine, heparin, antibiotics and oxygen, the patient improved without the need of mechanical ventilation. Initially seen signs of right heart dilatation diminished 3 days after onset of therapy. Apart from pulmonal manifestation no relevant organ damage was observed. The patient was discharged from the intensive care unit 9 days after intoxication and was submitted to psychiatric therapy. CONCLUSION: Lipoid pneumonia caused by intoxication with a mineral oil is a severe disease, whereas in the presented case a relative bland course of the disease has been seen. The employed therapy in this patient might be encouraging for a comparable treatment of pneumological complications resulting from similar clinical pictures.

Adult↗
PubMed2001

Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action.

The plasma level of NO(x), i.e., the sum of NO(2)- and NO(3)-, is frequently used to assess NO bioavailability in vivo. However, little is known about the kinetics of NO conversion to these metabolites under physiological conditions. Moreover, plasma nitrite recently has been proposed to represent a delivery source for intravascular NO. We therefore sought to investigate in humans whether changes in NO(x) concentration are a reliable marker for endothelial NO production and whether physiological concentrations of nitrite are vasoactive. NO(2)- and NO(3)- concentrations were measured in blood sampled from the antecubital vein and brachial artery of 24 healthy volunteers. No significant arterial-venous gradient was observed for either NO(2)- or NO(3)-. Endothelial NO synthase (eNOS) stimulation with acetylcholine (1-10 microg/min) dose-dependently augmented venous NO(2)- levels by maximally 71%. This effect was paralleled by an almost 4-fold increase in forearm blood flow (FBF), whereas an equieffective dose of papaverine produced no change in venous NO(2)-. Intraarterial infusion of NO(2)- had no effect on FBF. NOS inhibition (N(G)-monomethyl-l-arginine; 4-12 micromol/min) dose-dependently reduced basal NO(2)- and FBF and blunted acetylcholine-induced vasodilation and NO release by more than 80% and 90%, respectively. In contrast, venous NO(3)- and total NO(x) remained unchanged as did systemic arterial NO(2)- and NO(3)- levels during all these interventions. FBF and NO release showed a positive association (r = 0.85; P < 0.001). These results contradict the current paradigm that plasma NO(3)- and/or total NO(x) are generally useful markers of endogenous NO production and demonstrate that only NO(2)- reflects acute changes in regional eNOS activity. Our results further demonstrate that physiological levels of nitrite are vasodilator-inactive.

Acetylcholine↗
PubMed2001

The nitric oxide-induced reduction in cardiac energy supply is not due to inhibition of creatine kinase.

OBJECTIVES: While nitric oxide (NO) is a potent vasodilator already in the nM range, a cGMP-independent negative inotropic effect is observed at higher concentrations. Since inhibition of creatine kinase (CK) by NO-induced nitrosylation has been proposed as a possible mechanism of action, we measured the flux through CK in the intact heart. METHODS: In saline perfused, paced guinea pig hearts 31P NMR spectroscopy was employed to directly assess the cardiac energy status, i.e. free energy of ATP hydrolysis (DeltaG(ATP)) and flux through CK using magnetization transfer in absence and presence of NO. RESULTS: NO (50 microM) doubled coronary flow and induced a rapid drop in left ventricular developed pressure (39+/-10 vs. 81+/-10 mmHg) and MVO(2) (1.3+/-0.8 vs. 3.7+/-0.5 micromol/min/g) (n=7). This effect was associated with an immediate decrease in phosphocreatine (PCr) (-69%) and DeltaG(ATP). During the subsequent 35 min of NO infusion cardiac function and MVO(2) remained depressed, while PCr partially recovered. NO had no effect on the unidirectional forward flux through CK (98 +/- 21 vs. 99 +/- 20 micromol/min/g, n=7) which was 5- to 10-fold greater than the rate of ATP turnover. Upon cessation of NO infusion both cardiac function and PCr rapidly returned to baseline values. The NO-induced fall in the myocardial energy status was associated with an increase in mitochondrial NADH (n=7) as assessed by surface fluorescence. The observed change in fluorescence was similar to that observed with short term ischemia. CONCLUSION: The NO-mediated depression of myocardial function, MVO(2) and energy status is not mediated by changes in CK flux. Most likely a partial blockade of mitochondrial oxidative phosphorylation at the level of cytochrome c oxidase is responsible for this effect.

Animals↗
PubMed2001

[Interaction of the coronary macro- and microcirculation].

In the following the impact of epicardial vessels on flow regulation in downstream resistive arteries and, vice versa, the potential influence of coronary microvascular disease on upstream conduit arteries will be reviewed. There is ample evidence that coronary artery disease of epicardial vessels leads to microvascular dysfunction not only due to a flow limiting stenoses with an altered regulation of vessel tone in the intra- and poststenotic segments, but also via distal microembolization of atherosclerotic material derived from upstream plaques. On the other hand, patients with hypertensive microvascular disease frequently reveal a disturbed endothelium-dependent and -independent regulation of epicardial vessel tone, although angiographic appearance is regular. Most strikingly, it could be demonstrated that in these patients with microvascular disease the incidence of coronary artery disease of epicardial vessels is increased several-fold as compared to age-matched populations. These findings suggest that hypertensive microvascular disease independent from the direct effect of hypertension on epicardial vessel affects upstream conduit arteries. Therefore a thorough and careful follow up of hypertensive patients with initially normal coronary arteriograms but preexistent microvascular disease appears advisable.

Animals↗
PubMed2001

[Determination of right ventricular ejection fraction by thermodilution catheter technique during exercise: a comparison with radionuclide ventriculography].

Since the development of a Swan-Ganz Thermodilution Ejection Fraction Catheter, several studies have been published which compare this technique for obtaining right ventricular ejection fraction (RVEFTD) with alternative methods. However, the reliability of RVEFTD measurements under exercise conditions remains undetermined. Therefore, the aim of the present study was to evaluate RVEFTD with the Gated Blood Pool method (RVEFGBP) under exercise conditions. Twenty patients with different cardiac diseases (coronary artery disease, valvular incompetence, cardiomyopathy) underwent right heart catheterization, including RVEFTD and simultaneous RVEFGBP determination at rest and during supine bicycle exercise. Cardiac index at rest-/exercise was 2.9 +/- 0.8/5.7 +/- 2.2 l/min/m2, mean pulmonary artery pressure was 15 +/- 5/25 +/- 8 mmHg, RVEFTD was 38 +/- 6/41 +/- 11% and RVEFRNV was 39 +/- 6/43 +/- 8%. Linear regression analysis showed a significant correlation between RVEFTD and RVEFGBP at rest (r = 0.72, p < or = 0.0005) and during exercise (r = 0.72, p < or = 0.0005). It is concluded that the Thermodilution Ejection Fraction Catheter is a useful device for reliable, repetitive and safe RVEF measurements, not only at rest but also under exercise conditions. This is clinically important, because RVEF, as a sensitive parameter of primary or secondary right ventricular dysfunction, can be determined in the course of standard right heart catheterization.

Adult↗
PubMed2001

Vineberg graft: flow reserve of bilateral implantation after 27 years.

We report a patient who underwent bilateral internal thoracic artery implantation into the myocardium known as a Vineberg procedure 27 years ago. Coronary angiography and Doppler echocardiography revealed patent grafts with total occlusion of all native coronary arteries. We measured flow velocities at rest and under stress conditions with noninvasive ultrasonic Doppler echocardiography. The flow patterns in both grafts were biphasic as in native coronary arteries. Under stress conditions no increase in flow was detectable as a marker of end-stage coronary artery disease with refractory angina pectoris.

Angina Pectoris↗