Archiv für Kreislaufforschung

L-type calcium channels play an important role in excitation-contraction coupling. After cardiomyocyte depolarization L-type calcium channels open and Ca2+ ions enter the cell. These small Ca2+ inward currents trigger calcium release from the junctional sarcoplasmic reticulum, a process called calcium-induced calcium release. Subsequently, the cytosolic Ca2+ concentration rises rapidly to levels that initiate contraction. In heart failure calcium-induced calcium release is disturbed, and in this review we focus on the L-type calcium channel and its contribution to this defective excitation-contraction coupling.

Nach den heute vorliegenden experimentellen Befunden verschiedener Untersucher gibt es in der Skelettmuskulatur eine nutritive und eine nicht-nutritive (“Kurzschluß”-) Durchblutung. Die nicht-nutritive Durchblutung wird durch Erregung der sympathischen cholinergischen “Vasodilatoren”-nerven bzw. durch intravasale Acetylcholinzufuhr gesteigert. Die Voraussetzung für eine ausreichende Blutversorgung sowohl der ruhenden wie der arbeitenden Muskelfasern ist eine adäquate Öffnung nutritiver Kapillaren mit den vorgeschalteten Arteriolenund eine adäquate Schließung nicht-nutritiver Gefäße. Ein Versagen dieser lokalen Regelung kann trotz normaler Gesamtstromstärke die Ursache einer mangelhaften Versorgung der Muskelfasern sein. Deshalb darf die Gesamtstromstärke nicht als Maß der effektiven Skelettmuskeldurchblutung angeschen werden.

We have examined the sodium-calcium exchange stoichiometry in Langendorff-perfused rabbit hearts using gamma-emitting tracers under conditions of sodium pump inhibition. Following a 60-min perfusion with 105 acetylstrophanthidin, and extracellular concentrations [Na]o=70 mM and [Ca]o=300 μM, intracellular sodium rose to 59.2 mM. At this point an increase in extracellular calcium [Ca]o=1.52 mM) caused a net efflux of sodium, but an increase in sodium [Na]o=105 mM) caused no measurable change. When sodium and calcium were simultaneously increased according to the ratio [Na]o)n/[Ca]o=[Na]o ′)n/[Ca]o ′, a sodium efflux is observed when n=4, but not when n=3. These results are consistent with an exchange stoichiometry of 3 Na+ for each Ca2+ ion, but not values of 4 or more.

Chronic atrial fibrillation (AF) is characterized by a remodeling process which involves the development of fibrosis. Since angiotensin II has been suspected to be involved in this process, the aim of our study was to investigate a possible influence of an ACE–I therapy in patients with chronic AF regarding the occurrence of left atrial structural remodeling. Atrial tissue samples were obtained from patients with lone chronic AF or sinus rhythm (SR). Collagen I, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) protein expression were measured by quantitative Western Blotting techniques and calculated as mean ± SEM. Histological tissue samples were used for calculating microvessel density (microvessel/mm2 ± SEM). In AF, the collagen amount was higher (1.78 ± 0.21; p = 0.01) vs. SR (0.37 ± 0.07) accompanied by declining microcapillary density (AF: 145 ± 13 vs. SR: 202 ± 9; p = 0.01). Additionally, a negative correlation (p = 0.01) between collagen content and microcapillary density was observed. To investigate the influence of an ACE–I therapy on this remodeling process, patient groups were divided into AF and SR both with or without ACE–I. Interestingly, there was a significantly lower expression of collagen I in AF with ACE–I (1.04 ± 0.26) vs. AF without ACE–I treatment (2.07 ± 0.24, p = 0.02). The microcapillaries were not diminished in AF with ACE–I (180 ± 15) vs. SR with ACE–I (196 ± 9), but there was a significant rarification in AF without ACE–I (123 ± 18; p = 0.03). The expression of VEGF and bFGF did not reveal any significant differences. In patients undergoing ACE–I treatment: atrial structural remodeling was attenuated and the loss of atrial microcapillaries was prevented.

The postulate that ischemic preconditioning caused an attenuation in ischemia induced increases in tissue cAMP, and that this may pertain to the mechanism of ischemic preconditioning, was investigated in the isolated rat heart. A significant reduction in tissue cAMP in preconditioned hearts was observed for all time periods of global ischemia studied. The significance of this observation was evaluated by comparing the effect of antiadrenergic interventions on energy metabolism and post-ischemic functional recovery of both non-preconditioned and preconditioned hearts. The isolated perfused rat heart was used as experimental model. Six groups were studied: Non-preconditioned rat hearts: i) untreated controls (Non-PC), ii) reserpinised (Non-PC Res), iii) propranolol treated (10−7M) (Non-PC Prop); Preconditioned rat hearts: iv) preconditioned controls (PC), v) reserpinised (PC Res) and vi) propranolol (10−7M) treated (PC Prop). After 25 min global ischemia the concentration of cAMP was increased by 79.6% in the Non-PC group. This increase was attenuated in all of the treated groups, although in varying degrees. Energy utilization in these hearts also differed markedly between the groups. Functional recovery was however similar in all Non-PC and PC treated groups and significantly superior to that of Non-PC control hearts. Prior reserpinisation mimicked the protective effect of preconditioning on energy metabolism and functional recovery. To determine the significance of attenuation of the increase in cAMP in the protection conferred by preconditioning, hearts were pretreated with forskolin (10−6M). This caused an accumulation of tissue cAMP in preconditioned hearts to similar absolute values as seen in untreated non-preconditioned hearts during 25 min global ischemia. However, the percentage increase in forskolin-pretreated preconditioned hearts during sustained, ischemia was only 50% vs. 71% in non-preconditioned hearts treated with forskolin, confirming an attenuated β-response induced by preconditioning. Forskolin treatment of preconditioned hearts did not abolish the protective effect. The findings suggest that the protection against ischemic damage conferred by preconditioning is associated with an attenuated β-adrenergic response. However, whether the changes in cAMP occurring during sustained global ischemia is the cause or consequence of the elicited protection, remains to be established.

Sinus node recovery time (SRT), the pacing rate with the maximal SRT, and calculated sinoatrial conduction time (SACT) were studied by overdrive atrial pacing and programmed premature atrial stimulation in 78 patients before and after the application of several antiarrhythmic drugs or of atropine. The maximu SRT was usually observed at lower rates of atrial pacing after application of a drug that prolonged SACT, whereas the opposite behaviour was observed in the majority of cases in whom the drug tested shortened calculated SACT. However, this relationship was not observed in all cases which may be due to random changes of sinus node automaticity or sinoatrial conduction, or to the inability of programmed premature atrial stimulation to detect changes of SACT. The results of this study further substantiate the importance of the properties of sinoatrial conduction for achieving a maximal depression of sinus node activity during high rate atrial pacing.

Über 600 an einem langen Ekg einer gesunden Versuchsperson gemessene Paare zusammengehöriger RR- und QT-Werte werden korrelationsund regressionsstatistisch bearbeitet. Es stellt sich dabei heraus:

In echocardiography, there is still a need for a better tool to quantify regional myocardial function. Doppler myocardial imaging (DMI) allows the calculation of local myocardial velocity profiles for segmental motion in both the radial and longitudinal direction. From the local velocity profile data, 1-dimensional regional myocardial strain rates (SR) and strain (ε) can now be calculated. These new deformation indices more accurately define regional function compared to velocities as they are independent of overall heart motion. This paper will define the normal segmental velocity, SR and ε profiles and their relationship with global mechanical event markers. It will also define the changes in local velocity and deformation characteristics, which are induced by disease and the current experimental and clinical status of this new quantitative ultrasound tool.

Experiments were performed on 39 anaesthetized open-chest dogs (BW 16–33 kg) to examine the effect of lidocaine on the frequency of primary ventricular fibrillation (VF) and the time course of the ventricular fibrillation threshold (VFT) (train of stimuli-method) following acute coronary artery occlusion, and also to study the effects of lidocaine on the VFT of non-ischaemic heart at different therapeutic and high non-therapeutic doses. At effective plasma levels of lidocaine usually reached in clinical therapy (130–480 μg/l) there was no measurable increase in VFT compared to control values. The drop in VFT following acute ligation of the left anterior descending coronary artery (LAD) was neither eliminated nor even merely diminished. After occlusion of the left circumflex coronary artery (CIR), the incidence of spontaneous VF was not reduced in comparison to a control group. With regard to the doses administered and the plasma levels of lidocaine achieved, only the application of clinically extremely high or toxic doses resulted in increases in VFT in the non-ischaemic heart. Therefore it cannot be expected that there exists a protective effect of clinically recommended doses of lidocaine in preventing primary VF during the early phase of arrhythmia following acute coronary occlusion.