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Biomedical subjects

Christian E Zaugg

Publications and source records attributed to Christian E Zaugg.

8 recordsLinked to original sources
PubMed2007

Bradykinin is a mediator, but unlikely a trigger, of antiarrhythmic effects of ischemic preconditioning.

OBJECTIVE: Brief reversible ischemic episodes (ischemic preconditioning, IPC) protect the heart against arrhythmias during a subsequent prolonged low-flow ischemia. We have recently shown that this protection involves release of bradykinin, activation of bradykinin B2 receptors followed by opening of sarcolemmal, but not mitochondrial ATP-sensitive K+ channels. The goal of this study was to clarify a trigger and/or mediator role of bradykinin in the antiarrhythmic effects of IPC during low-flow ischemia. METHODS: Isolated perfused rat hearts underwent 60 minutes of low-flow ischemia induced by reducing perfusion pressure followed by 60 minutes of reperfusion. Preconditioning was induced by 2 x 5 minutes episodes of zero-flow ischemia. In yet other groups, preconditioned or non-preconditioned hearts were treated either with bradykinin (10 nmol/L) or with HOE 140 (bradykinin B2 receptor antagonist, 100 nmol/L). RESULTS: IPC reduced the number of ventricular premature beats, as well as the incidence of ventricular tachycardia and of ventricular fibrillation during low-flow ischemia. In addition, this protection was abolished by HOE 140 given during low-flow ischemia. Pharmacological preconditioning using short bradykinin perfusion instead of IPC did not show antiarrhythmic effects. However, bradykinin administered during low-flow ischemia and reperfusion reduced the number of ventricular premature beats and the incidence of ventricular tachycardia and of ventricular fibrillation during low-flow ischemia. CONCLUSION: Bradykinin is a mediator, but unlikely a trigger, of antiarrhythmic effects of IPC during low-flow ischemia.

Animals↗
PubMed2004

Current concepts on ventricular fibrillation: a vicious circle of cardiomyocyte calcium overload in the initiation, maintenance, and termination of ventricular fibrillation.

Based on recent experimental studies, this review article introduces the novel concept that cardiomyocyte Ca2+ and ventricular fibrillation (VF) are mutually related, forming a self-maintaining vicious circle in the initiation, maintenance, and termination of VF. On the one hand, elevated myocyte Ca2+ can cause delayed afterdepolarizations, triggered activity, and consequently life-threatening ventricular tachyarrhythmias in various pathological conditions such as digitalis toxicity, myocardial ischemia, or heart failure. On the other hand, VF itself directly and rapidly causes progressive myocyte Ca2+ overload that maintains VF and renders termination of VF increasingly difficult. Accordingly, energy levels for successful electrical defibrillation (defibrillation thresholds) increase as both VF and Ca2+ overload progress. Furthermore, VF-induced myocyte Ca2+ overload can promote re-induction of VF after defibrillation and/or postfibrillatory myocardial dysfunction (postresuscitation stunning) due to reduced myofilament Ca2+ responsiveness. The probability of these adverse events is best reduced by early detection and rapid termination of VF to prevent or limit Ca2+ overload. Early additional therapy targeting transsarcolemmal Ca2+ entry, particularly during the first 2 min of VF, may partially prevent myocyte Ca2+ overload and thus, increase the likelihood of successful defibrillation as well as prevent postfibrillatory myocardial dysfunction.

Journal Article↗
PubMed2004

Antiarrhythmic effect of ischemic preconditioning during low-flow ischemia. The role of bradykinin and sarcolemmal versus mitochondrial ATP-sensitive K(+) channels.

Short episodes of ischemia (ischemic preconditioning) protect the heart against ventricular arrhythmias during zero-flow ischemia and reperfusion. However, in clinics, many episodes of ischemia present a residual flow (low-flow ischemia). Here we examined whether ischemic preconditioning protects against ventricular arrhythmias during and after a low-flow ischemia and, if so, by what mechanism(s). Isolated rat hearts were subjected to 60 min of low-flow ischemia (12% residual coronary flow) followed by 60 min of reperfusion. Ischemic preconditioning was induced by two cycles of 5 min of zero-flow ischemia followed by 5 and 15 min of reperfusion, respectively. Arrhythmias were evaluated as numbers of ventricular premature beats (VPBs) as well as incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF) during low-flow ischemia and reperfusion. Ischemic preconditioning significantly reduced the number of VPBs and the incidence of VT and of VF during low-flow ischemia. This antiarrhythmic effect of preconditioning was abolished by HOE 140 (100 nM), a bradykinin B(2) receptor blocker. Similar to preconditioning, exogenous bradykinin (10 nM) reduced the number of VPBs and the incidence of VT and of VF during low-flow ischemia. Furthermore, the antiarrhythmic effects of both ischemic preconditioning and bradykinin were abolished by glibenclamide (1 microM), a non-specific blocker of ATP-sensitive K(+) (K(ATP)) channels. Finally, the antiarrhythmic effects of both ischemic preconditioning and bradykinin were abolished by HMR 1098 (10 microM), a sarcolemmal K(ATP) channel blocker but not by 5-hydroxydecanoate (100 microM), a mitochondrial K(ATP) channel blocker. In conclusion, ischemic preconditioning protects against ventricular arrhythmias induced by low-flow ischemia, and this protection involves activation of bradykinin B(2) receptors and subsequent opening of sarcolemmal but not of mitochondrial K(ATP) channels.

Animals↗
PubMed2004

Losartan but not enalaprilat acutely reduces reperfusion ventricular tachyarrhythmias in hypertrophied rat hearts after low-flow ischaemia.

Based on clinical and experimental studies, angiotensin II receptor blockers and angiotensin converting enzyme inhibitors have been proposed to exert acute anti-arrhythmic effects in heart failure patients. Therefore, the goal of this study was to assess acute anti-arrhythmic effects of losartan and enalaprilat in hypertrophied rat hearts during low-flow ischaemia and reperfusion. In dose-finding experiments in non-hypertrophied isolated perfused hearts, we performed dose-response curves of losartan and enalaprilat studying monophasic action potential duration at 90% repolarisation (MAPD(90%)) and ventricular fibrillation (VF) threshold. Subsequently, we determined the effects of losartan and enalaprilat (in therapeutically relevant concentrations) on ventricular tachyarrhythmias induced by low-flow ischaemia/reperfusion in hearts demonstrating left ventricular (LV) hypertrophy 70 days after aortic banding. We found that neither drug significantly affected MAPD(90%) (1 nM-1 mM) or VF threshold (1 microM losartan and 10 microM enalaprilat) in non-hypertrophied hearts. Similarly in hypertrophied hearts, neither drug significantly affected the incidence or the duration of ventricular tachyarrhythmias (ventricular tachycardia and VF) during low-flow ischaemia. However, 1 microM losartan significantly reduced the duration of ventricular tachyarrhythmias during reperfusion. In conclusion, neither losartan nor enalaprilat is acutely anti-arrhythmic in hypertrophied rat hearts during low-flow ischaemia. During reperfusion, however, losartan but not enalaprilat exerts acute anti-arrhythmic effects.

Action Potentials↗
PubMed2003

Rate response of a closed-loop stimulation pacing system to changing preload and afterload conditions.

Closed-loop stimulation (CLS) is a new sensor concept for rate adaptive pacing measuring changes in the unipolar right ventricular impedance, which correlates to changes of the right ventricular contractility and reflects the autonomic nervous innervation of the heart. Some patients do not tolerate the CLS mode because of inappropriate tachycardia, mainly related to postural changes. This study tested if the rate response of the CLS sensor is influenced not only by myocardial contractility but also by rapid changes in right ventricular filling. In 12 patients (10 men, median age 77 years) with a Biotronik Inos(2)-CLS DDDR pacemaker and 14 controls (13 men, median age 59 years) head-up tilt and handgrip testing was performed to provoke rapid changes in pre- and afterload. Tilting the pacemaker patients resulted in a nonphysiological steep increase of the sensor rate (increase >20 beats/min, peak after 1 minute, return to baseline within 2-3 minutes), which was significantly different from the control group, showing only a slight rise in intrinsic heart rate immediately after tilting. Simultaneously to the rapid increase in sensor rate, the pacemaker patients showed a marked orthostatic decline of systolic blood pressure. During handgripping, heart rate and blood pressure curves were similar in both groups. In patients with this CLS pacemaker, rapid preload reduction during head-up tilting caused an overshooting sensor rate increase, reproducing the authors' clinical observation of postural pacemaker tachycardia in some patients. Consequently, they concluded that the rate response of the CLS pacing system can be inappropriately influenced by rapid shifts of blood volume, affecting right ventricular filling.

Aged↗
PubMed2002

Non-invasive measurements of myocardial carbon metabolism using in vivo 13C NMR spectroscopy.

Despite their prime role in maintaining contractile performance, myocardial substrate uptake, substrate preference and metabolism are difficult to assess non-invasively. The objective of the present work was to extend the scope of cardiac 13C nuclear magnetic resonance (NMR) spectroscopy to the in vivo situation ('closed-chest model') and to quantitatively appraise myocardial metabolism in vivo. For this purpose, overnight-fasted Sprague-Dawley rats received intravenous infusions of non-radioactive 13C-labeled glucose, 3-hydroxybutyrate, and acetate as markers for glycolysis, metabolism of ketone bodies and direct incorporation into tricarboxylic acid (TCA) cycle, respectively. In vivo 13C NMR spectra (at 7 T) were acquired from the myocardium with a time resolution of 6 min. At the end of the infusion experiments, tissue extracts were prepared and further analyzed by high-resolution 13C NMR spectroscopy in order to corroborate the findings obtained in vivo. Accordingly, 3-hydroxybutyrate and acetate were rapidly extracted by the myocardium and supplied 42 +/- 6 and 53 +/- 9% of the acetyl-CoA for TCA cycle operation, whereas glucose, although also well extracted, did not contribute to myocardial oxidative metabolism. Myocardial TCA cycle turnover (V(TCA)) in vivo was estimated at 1.34 +/- 0.07 micromol/min/g wet weight, myocardial oxygen consumption (MVO2) at 2.95 +/- 0.16 micromol/min/g wet weight, exchange rate between alpha-ketoglutarate and glutamate (V(x)) at 1.22 +/- 0.08 micromol/min/g wet weight and rate of glutamine synthesis (V(gln)) at 0.14 +/- 0.02 micromol/min/g wet weight. The substantial synthesis of myocardial glutamine is in contrast to experiments with isolated and saline perfused hearts. In conclusion, it is demonstrated that 13C NMR spectroscopy of the heart in intact rats is feasible and provides new quantitative insight into myocardial substrate uptake, preference and metabolism in vivo.

3-Hydroxybutyric Acid↗
PubMed2002

Postresuscitation stunning: postfibrillatory myocardial dysfunction caused by reduced myofilament Ca2+ responsiveness after ventricular fibrillation-induced myocyte Ca2+ overload.

INTRODUCTION: Resuscitation from ventricular fibrillation (VF), particularly from prolonged VF, frequently is complicated by postfibrillatory myocardial dysfunction (postresuscitation stunning). We tested whether this dysfunction can be caused by reduced myofilament Ca2+ responsiveness after VF-induced myocyte Ca2+ overload. We also tested whether electrical defibrillation shocks contribute to this dysfunction. METHODS AND RESULTS: Myofilament Ca2+ responsiveness was estimated as ratio of left ventricular developed pressure over myocyte Ca2+ transient amplitudes (assessed as indo-1 fluorescence) in isolated perfused rat hearts before, during, and after VF (1.5 or 10 min) comparing three modes of defibrillation (biphasic electrical shocks, lidocaine, or spontaneous). We found that, independent of these defibrillation modes, myofilament Ca2+ responsiveness was significantly reduced, particularly after prolonged VF, although hearts were not ischemic or acidotic during and after VF (unchanged coronary flow, myocardial oxygen consumption, and pH of the coronary effluent). This reduction was associated with VF-induced myocyte Ca2+ overload and increasing or decreasing Ca2+ overload during VF (using 1 microM diltiazem or 6 mM extracellular calcium) led to parallel changes of myofilament Ca2+ responsiveness. However, myofilament Ca2+ responsiveness was not associated with the defibrillation shock energy (range 0.1-15.0 J/g wet heart weight). CONCLUSION: Postfibrillatory myocardial dysfunction can be caused by reduced myofilament Ca2+ responsiveness after VF-induced myocyte Ca2+ overload. Electrical defibrillation shocks (up to 15 J/g wet heart weight), however, do not significantly contribute to this dysfunction. Our findings suggest that early additional therapy targeting intracellular Ca2+ overload may normalize myocyte Ca2+ and partially prevent postresuscitation stunning.

Actin Cytoskeleton↗