Johannes Pleiner

Regular physical exercise improves endothelial function in heart transplant recipients

Background:u2002Impaired endothelial function is detectable in heart transplant (HTX) recipients and regarded as risk factor for coronary artery disease. We have studied whether endothelial function can be improved in HTX patients participating in a regular physical training program as demonstrated in patients with chronic heart failure, hypertension and coronary artery disease.

Acute Escherichia coli endotoxaemia decreases the plasma l-arginine/asymmetrical dimethylarginine ratio in humans.

Acute inflammation impairs vascular function. Based on the association between endothelial dysfunction and plasma concentrations of L-arginine and the endogenous nitric oxide synthase inhibitor ADMA (asymmetrical dimethylarginine), we hypothesized that the ratio between L-arginine and ADMA could be affected by experimental inflammation. Plasma concentrations of L-arginine, ADMA and SDMA (symmetrical dimethylarginine) were studied at baseline and 3.5 h after intravenous administration of Escherichia coli endotoxin [LPS (lipopolysaccharide), 20 units/kg of body mass; n =8] or placebo ( n =9) in healthy males. L-Arginine and dimethylarginines were quantified after solid-phase extraction by reversed-phase HPLC. Body temperature, heart rate and leucocyte count increased after LPS administration ( P <0.01 for all). LPS administration decreased plasma concentrations of L-arginine from 66 micromol/l [95% CI (confidence interval): 56, 88] at baseline to 48 micromol/l (CI: 40, 60) after 3.5 h ( P <0.02), but did not affect ADMA and SDMA concentrations. Consequently, the L-arginine/ADMA ratio declined significantly from a median of 159 (CI: 137, 193) to 135 (CI: 103, 146); a decrease of 25 (CI: -68, -13; P <0.02). L-Arginine, ADMA, SDMA and the L-arginine/ADMA ratio remained constant over time in controls. Acute inflammation reduces the L-arginine/ADMA ratio which could contribute to impaired vascular function.

Marked increase in vascular endothelial growth factor concentrations during Escherichia coli endotoxin-induced acute inflammation in humans.

Backgroundu2002 Bacterial endotoxins can induce the synthesis and release of vascular endothelial growth factor (VEGF), which may alter vascular permeability and cause vascular leakage.

Safety of a combined strength and endurance training using neuromuscular electrical stimulation of thighs muscles in patients with heart failure and bipolar sensing cardiac pacemakers

ZusammenfassungFür Patienten mit schwerer chronischer Herzinsuffizienz ist Ausdauer- und Krafttraining durch neuromuskuläre Elektrostimulation (NMES) eine effektive und nicht belastende Alternative zum aktiven Training. Wegen möglicher elektromagnetischer Interferenz werden Herzschrittmacherpatienten häufig von einer NMES-Behandlung ausgeschlossen. Ziel dieser Pilotstudie war die Untersuchung der Sicherheit eines kombinierten NMES-Ausdauer- und Krafttrainingsprotokolles für Patienten mit Herzschrittmachern.In die Studie wurden sieben Patienten mit schwerer chronischer Herzinsuffizienz und implantierten Herzschrittmachern mit bipolar wahrnehmenden Elektroden eingeschlossen und ein ärztlich supervidiertes kombiniertes Ausdauer- und Krafttraining mittels NMES unter Pulsmonitoring durchgeführt. Das NMES-Protokoll bestand aus biphasischen, symmetrischen Rechteckimpulsen mit unterschiedlichen Frequenzen von 8 Hz bis 50 Hz, Impulsdauern bis 60 s (8 Hz), 4s (15 Hz), 4 s (30 Hz) und 6 s (50 Hz), sowie Amplituden bis ±100 mA (alle Frequenzen). Die Stromapplikation erfolgte über Oberflächenelektroden (8×13 cm) im Bereich der Streck- und Beugemuskulatur beider Oberschenkel.Eine akute elektromagnetische Interferenz trat im Verlauf eines Sicherheitschecks (Telemetriemonitoring) vor Beginn der NMES-Therapie bei keinem der Patienten auf. Den 7 Patienten wurden während jeweils 20 NMES-Therapie-Einheiten komplikationslos bei insgesamt 23.380 Einschaltphasen 2.194,08×103 Stimuli appliziert. Es wurden keine Änderungen der simultan registrierten Herzfrequenz detektiert und keine Fehlfunktion des Schrittmachers festgestellt.Die Durchführung eines kombinierten NMES-Ausdauer-und Krafttrainingsprogrammes der Oberschenkelmuskulatur erscheint bei Patienten mit Herzinsuffizienz und implantierten bipolaren Herzschrittmachern unter Berücksichtigung der beschriebenen Elektrodenlagen und Parametergrenzen sicher.SummaryNeuromuscular electrical stimulation (NMES) is an effective and non-strenuous therapy to enhance the strength and endurance capacity of the skeletal muscles in patients with severe chronic heart failure. NMES in patients with pacemakers is controversial because potential electromagnetic interference may result in pacemaker malfunction. Therefore, such patients are in general excluded from NMES. The aim of this pilot study was to evaluate the safety of a combined NMES protocol to increase strength and endurance capacity of the skeletal muscles in patients with heart failure and implanted pacemakers.Seven patients with chronic heart failure and implanted cardiac pacemakers with bipolar sensing leads received NMES treatment of thigh muscles, using a combined protocol comprising biphasic, symmetric, rectangular constant current impulses at different frequencies (8–50 Hz), pulse width up to 60 s (8 Hz), 4 s (15 Hz), 4 s (30 Hz), and 5 s (50 Hz), and amplitudes up to ±100 mA (all frequencies) applied to both knee extensor and flexor muscles via surface electrodes (8×13 cm each).Acute electromagnetic interference during a safety procedure (telemetric monitoring) before therapeutic NMES application was not observed in any of the patients. The 7 patients received during 20 therapeutic NMES sessions a total of 23,380 on-phases, comprising 2194.08×103 biphasic electrical pulses, without adverse events. Heart rate monitoring during stimulation and pacemaker interrogation revealed no abnormalities.NMES treatment of thigh muscles using a combined NMES protocol to enhance strength and endurance capacity appears to be safe in patients with heart failure and implanted pacemakers with bipolar sensing, as far as the described electrode configuration and parameter range is applied.

Endothelin ETA receptor-subtype specific antagonism does not mitigate the acute systemic or renal effects of exogenous angiotensin II in humans

Background Angiotensin II (Ang II) is assumed to play a pathophysiological role in a variety of vascular diseases. Animal studies indicate that these effects are partly attributed to stimulation of endothelin‐1 (ET‐1) release. The aim of the present study was to investigate whether the acute effects of Ang II on systemic and renal haemodynamics in healthy subjects can be influenced by endothelin ETA‐receptor blockade.

Medikamenteninteraktionen in der Geriatrie

SummaryDrug interactions are often seen in elder patients due to polymedication. They can lead to unwanted side effects attended with unspecific symptoms such as vertigo, lateropulsion, fatigue or confusion. This can result in a prescribing cascade. Interactions can take place on all pharmacodynamic and pharmacokinetic levels, whereas the CYP enzyme-dependent metabolism seems to play a key role. The incidence of drug interactions is quite high and clinical relevant interactions are also not uncommon. Especially drugs with a low therapeutic index are more likely to be the target of clinical relevant interactions. However, most of the drug interactions can be managed by dose-reduction or by replacing one of the possibly interacting drugs. An important point is to remember the possibility of drug interactions.ZusammenfassungArzneimittelinteraktionen treten vor allem bei älteren Patienten aufgrund der Vielmedikation (Polypragmasie) auf und können zu unerwünschten Wirkungen führen. Diese können sich in unspezifischen Symptomen wie Schwindel, Fallneigung, Müdigkeit oder Verwirrtheitszuständen äußern und durch Fehleinschätzung eine Verschreibungskaskade auslösen. Medikamentenwechselwirkungen können auf allen Ebenen der Pharmakodynamik und Pharmakokinetik stattfinden, wobei vor allem der CYP-Enzym abhängige Metabolismus von besonderer Bedeutung ist. Arzneimittelinteraktionen treten häufig auf und auch klinisch relevante Interaktionen sind nicht selten und kommen auch vor allem bei Medikamenten mit einer geringen therapeutischen Breite vor. Diese sind zumeist durch eine Dosisreduktion oder einen Wechsel auf ein anderes Medikament beherrschbar. Aber auch bei unspezifischen Symptomen sollte eine Arzneimittelineraktion in Betracht gezogen werden.Drug interactions are often seen in elder patients due to polymedication. They can lead to unwanted side effects attended with unspecific symptoms such as vertigo, lateropulsion, fatigue or confusion. This can result in a prescribing cascade. Interactions can take place on all pharmacodynamic and pharmacokinetic levels, whereas the CYP enzyme-dependent metabolism seems to play a key role. The incidence of drug interactions is quite high and clinical relevant interactions are also not uncommon. Especially drugs with a low therapeutic index are more likely to be the target of clinical relevant interactions. However, most of the drug interactions can be managed by dose-reduction or by replacing one of the possibly interacting drugs. An important point is to remember the possibility of drug interactions.

Placebo effects and placebo control in clinical trials

The history of placebo goes back several centuries. These “dummy pills” have been used by healers and physicians worldwide, ignored by the official medical community