Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

Electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic ischemic heart disease

BACKGROUND: Bone marrow cell injection has been introduced to treat patients with ischemic heart disease. However, focal application of bone marrow cells may generate an arrhythmogenic substrate. OBJECTIVES: To assess the electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia. METHODS: Bone marrow was aspirated in 20 patients (65+/-11 years, 19 male) with drug-refractory angina and myocardial ischemia. Electroanatomical mapping (NOGA, Biosense-Webster, Waterloo, Belgium) was performed during mononuclear cell isolation. Areas for cell injection were selected based on the localization of ischemia on SPECT. These areas were mapped in detail to evaluate local bipolar electrogram duration, amplitude and fragmentation. Mononuclear cells were injected in the ischemic area with the NOGA system. SPECT and electroanatomical mapping were repeated at 3 months. Holter monitoring was repeated at 3 and 6 months. RESULTS: SPECT revealed a decrease in the number of segments with ischemia (3.5+/-2.5 vs. 1.1+/-1.0 at 3 months; P<0.01) and an increased left ventricular ejection fraction (44+/-13% vs. 49+/-17% at 3 months; P=0.02). The number of ventricular premature beats remained unchanged (10+/-24x10(2)/24h vs. 8+/-23x10(2)/24h at 3 months (P=NS) and 12+/-30x10(2)/24h at 6 months (P=NS)). At 3 months follow-up, bone marrow cell injection did not prolong electrogram duration (15.9+/-4.6 ms vs. 15.6+/-4.0 ms; P=NS), decrease electrogram amplitude (3.8+/-1.5 mV vs. 3.8+/-1.5 mV; P=NS), or increase fragmentation (2.0+/-0.5 vs. 1.9+/-0.4; P=NS). CONCLUSION: Intramyocardial bone marrow cell injection does not increase the incidence of ventricular arrhythmias and does not alter the electrophysiological properties of the injected myocardium.     

Blockade of the human cardiac K+ channel Kv1.5 by the antibiotic erythromycin

Erythromycin administration has been associated with a prolongation of cardiac repolarization in certain clinical settings. This could be due to blockade of voltage-dependent K⁺ channels in the human heart. For this reason we examined the effects of erythromycin on a rapidly activating delayed rectifier K⁺ channel (Kv1.5) cloned from human heart and stably expressed in human embryonic kidney cells. When examined using the whole-cell patch clamp technique, erythromycin (100 μM) blocked Kv1.5 current in a time-dependent manner but required prolonged exposure to do so. However, when we examined Kv1.5 current using inside-out macropatches, erythromycin applied to the cytoplasmic surface rapidly (within 1-2 min) inhibited Kv1.5 current with an IC₅₀ value of 2.6 x 10^-5M (1.7 - 3.9 x 10^-5M, 95% C.L.). The main effect of erythromycin was to accelerate the rate of Kv1.5 current decay thereby reducing the current at the end of a prolonged voltage-clamp pulse. Erythromycin also blocked Kv1.5 current in both a voltage- and frequency-dependent manner but had little effect on the activation kinetics, deactivation kinetics, or the steady-state inactivation properties of Kv1.5. These data suggest that erythromycin acts as a blocker of an activated state of the Kv1.5 channel and that it may access its binding site from the intracellular face of the channel. This study is the first to examine the effects of erythromycin on a cloned human cardiac K⁺ channel. It is concluded that erythromycin blocks Kv1.5 at clinically relevant concentrations. Blockade of voltage-dependent K⁺ channels in the heart could contribute to the alterations in cardiac repolarization that have been observed with erythromycin. Received: 22 November 1996 / Accepted: 26 February 1997     

Rhabdomyoma of the heart with intrapericardial expansion

A rare case of a rhabdomyoma originating from the surface of the right atrium in a 20-year-old female is reported. The tumor showed electrical activity and caused both outflow obstruction and tamponade symptoms. It was successfully removed by a right-sided thoracotomy. The clinical course, diagnostic investigations, and the therapeutical approach of this rare lesion are discussed.     

Importance of spatiotemporal heterogeneity of cellular restitution in mechanism of arrhythmogenic discordant alternans

BACKGROUND: Spatially discordant cellular alternans form a substrate for development of unidirectional block and ventricular fibrillation. However, the mechanisms responsible for discordant alternans remain poorly understood. Previous work suggests electrical restitution is critical to the development of alternans in single cells. OBJECTIVES: The purpose of this study was to investigate the hypothesis that spatial and temporal heterogeneities of restitution underlie the mechanism eliciting discordant alternans. METHODS: Steady-state pacing was used to elicit concordant cellular alternans in nine Langendorff-perfused guinea pig hearts. A single extrastimulus (S2) was applied every 51st beat following either the even or the odd beat of alternans. The cellular response to S2 was determined using optical mapping to generate action potential duration (APD) restitution curves from 256 ventricular sites for both the even and the odd beats. RESULTS: Restitution kinetics were temporally heterogeneous during alternans, as restitution curves between the even and the odd beats differed significantly. Temporal heterogeneity was quantified by the average separation of restitution between the two curves, or Delta-restitution. Delta-Restitution was spatially heterogeneous and proportional to the amount of alternans at a given ventricular site. A computer simulation based on the experimental results showed the mechanism of discordant alternans was dependent on both spatial and temporal heterogeneities of restitution. CONCLUSION: Both temporal and spatial heterogeneities of restitution exist during cellular alternans in the intact heart. Temporal heterogeneities of restitution, quantified by Delta-restitution, are proportional to the magnitude of cellular alternans. The combination of spatial and temporal heterogeneities of restitution may underlie the genesis of discordant alternans.     

Pharmacology of KB‐R7943: A Na+–Ca2+ exchange inhibitor

The Na⁺–Ca²⁺ exchange (NCX) system plays a pivotal role in regulating intracellular Ca²⁺ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca²⁺‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases.     

Electrode Positioning for Reliable Telemetry ECG Recordings During Social Stress in Unrestrained Rats

We describe a surgical procedure for optimizing the location of telemetry ECG leads in rats. The new location was aimed at obtaining an accurate representation of ECG features throughout the cardiac cycle by limiting the voltage instability usually observed during intense somatomotor activity and improving the signal-to-noise ratio. The two electrodes (wire loops) were fixed on the dorsal surface of the xiphoid process and in the anterior mediastinum close to the right atrium. The implantation procedure was fast, little invasive, and allowed animals to completely recover from intervention. The performance of the “improved” location (IL, n = 10) with respect to two subcutaneous (SC) positionings (“conventional positioning,” CSP, n = 5; “updated location,” USL, n = 5) was evaluated by comparing ECGs obtained in baseline, stress and recovery conditions and during different behavioral activities (immobility and grooming). The resident-intruder test (emotional/physical challenge) was chosen as experimental stress paradigm. The noise level of ECGs obtained from IL rats was lower than in CSP and USL animals, in all recording conditions. Percentages of correctly recognized beats (CRBs) over the total number of beats (TBs) were significantly higher in IL rats than in CSP and USL animals, both in baseline conditions (99% vs. 11% and 40%) and situations involving high somatomotor activity (stress: 97%, 5% and 16%; recovery: 97%, 7%, and 15%) (p < 0.01). The performance of IL as compared to CSP and USL was also better when percentages during grooming and immobility were considered (grooming: 93% vs. 4% and 23%; immobility: 97%, 6%, and 33%; p < 0.01).     

Use of ivabradine for treatment of junctional ectopic tachycardia in post congenital heart surgery

Cardiac surgeries especially involving crux of the heart as performed in tetralogy of Fallot (TOF) and pulmonary stenosis are mainly responsible for junctional ectopic tachycardia (JET). Diversified antiarrhythmic agents have been used in an impressive way to treat JET but showed suboptimal efficacy and varied associated adverse effects. But, ivabradine has proved as final crusader for its treatment. We report our initial experience of 4 cases in last 6 months with ivabradine in the management of postoperative JET. Encouraged by various reports and our increasing experience with ivabradine in heart failure population, we have moved to ivabradine as the first drug of choice for postoperative JET. Bradycardia was the only significant adverse effect in our series. The availability of atrial and ventricular pacing wires or at least transvenous temporary pacing should be ensured before starting ivabradine.     

An experimental model of the production of early after depolarizations by injury current from an ischemic region

An ischemic myocardial region contains cells with a depolarized resting membrane potential. This depolarization leads to an intercellular current flow between the ischemic region and the surrounding normal myocardial cells which has been termed an injury current. We have devised an experimental model system in which an isolated guinea pig ventricular cell is electrically coupled to a model depolarized cell in order to evaluate the effects of this injury current on the electrical properties of a normal ventricular cell exposed to drugs which increase calcium current or decrease potassium current. Using low doses of isoproterenol, forskolin, or Bay K 8644 (or 8-bromo-cyclic adenosine monophosphate in the pipette) we found that the action potential duration of the isolated cell was lengthened, but that early after depolarizations (EADs) were not produced unless the cell was also coupled to a depolarized cell model representing an adjacent ischemic region. A similar prolongation of the action potential was produced by low doses of quinidine, but EADs were not produced unless coupling to a depolarized cell model was added. EADs could not be produced in any cells in the absence of the drugs even though the coupling to the depolarized cell model was increased up to the level at which the action potential was indefinitely prolonged. At higher isoproterenol concentrations, EADs or spontaneous activity were produced without coupling to the depolarized cell model. Under these conditions, coupling of the cell to a cell model with normal resting membrane potential stopped the spontaneous activity and prevented the occurrence of EADs even with high levels of resistive coupling. These findings suggest that the electrotonic influences of a localized depolarized region can produce EADs if the calcium current magnitude is increased, which would be the case for sympathetic innervation.     

围手术期心脏起搏临床应用探讨

报道５８例非心脏手术的围手术期心脏起搏临床应用,重点讨论围手术期心脏起搏的方法与适应症。认为经静脉右室起搏疗效恒定可靠,适应症范围广。对伴有缓慢型或快速型心律失常的心脏病或潜在心脏病患者,围手术期心脏起搏适应症可适当放宽,以确保麻醉手术顺利进行