冠心灵对冠脉血流量、心肌收缩力和心电活动的影响

目的 :研究中药复方制剂冠心灵的心血管作用并初步探讨其作用机制。方法 :运用细胞内微电极技术、L angendorff离体心脏灌流和心率变异性功率谱分析等方法 ,研究冠心灵对心肌细胞动作电位的影响 ;观察其对冠脉血流量和心肌收缩力的作用 ;分析冠心灵对冠心病患者心率变异性的影响。结果 :冠心灵增强 Ca2 +跨膜内流 ;增加冠脉血流量和心肌收缩力 ;改善因缺血导致冠脉流量和心肌收缩力的下降 ;功率谱分析显示心迷走交感对心率的调控作用比升高。结论 :冠心灵有改善心肌缺血的作用。     

Determination of intracellular pH in the Langendorff-perfused guinea-pig heart by 31P nuclear magnetic resonance spectroscopy

The 31P NMR spectrum of freshly prepared guinea-pig heart perfused in the Langendorff mode at 37 degrees C with medium containing either glucose or pyruvate as an energy source exhibited no inorganic phosphate peak making the determination of intracellular pH from the chemical shift of this peak impossible. By incorporating 2-deoxyglucose-6-phosphate into the heart to act as an alternative pH indicator, intracellular pH was determined to be 6.98 +/- 0.02 (mean +/- S.E.M. for eight animals). 2-Deoxyglucose was not taken up and phosphorylated by guinea-pig heart in the presence of glucose. Uptake and phosphorylation did proceed if glucose was omitted from the perfusion medium, but a large inorganic phosphate peak was present in the initial spectrum prior to 2-deoxyglucose addition. With pyruvate as sole energy source, an inorganic phosphate peak was absent initially and 2-deoxyglucose was taken up and phosphorylated. During a 12 min period of global ischaemia at 20 degrees C, when inorganic phosphate was visible together with 2-deoxyglucose-6-phosphate, a close correlation was found between the pH estimated from the chemical shift of inorganic phosphate and 2-deoxyglucose-6-phosphate over the pH range 6.3 to 6.9.     

Transmembrane Voltage Changes Produced by Real and Virtual Electrodes During Monophasic Defibrillation Shock Delivered by an Implantable Electrode

Defibrillation Shock-Induced Virtual Electrodes. Introduction: Epicardial point stimulation produces nonuniform changes in the trans membrane voltage of surrounding cells with simultaneous occurrence of areas of transient positive and negative polarization. This is the phenomenon of virtual electrode. We sought to characterize the responses of epicardial ventricular tissue to the application of monophasic electric shocks from an internal transvenous implantable cardioverter defibrillator (ICD) lead.
Methods and Results: Langendorff-perfused rabbit hearts (n = 12) were stained with di-4-ANEPPS. A 9-mm-long distal electrode was placed in the right ventricle. A 6-cm proximal electrode was positioned horizontally 3 cm posteriorly and 1 cm superiorly with respect to the heart. Monophasic anodal and cathodal pulses were produced by discharging a 150-μF capacitor. Shocks were applied either during the plateau phase of an action potential (AP) or during ventricular fibrillation. Leading-edge voltage of the pulse was 50 to 150 V, and the pulse duration was 10 msec. Transmembrane voltage was optically recorded during application of the shock, simultaneously from 256 sites on a 11 × 11 mm area of the anterior right ventricular epicardium directly transmural to the distal electrode. The shock effect was evaluated by determining the difference between the AP affected by the shock and the normal AP. During cathodal stimulation an area of depolarization near the electrode was observed, surrounded by areas of hyperpolarization. The amplitude of polarization gradually decreased in areas far from the electrode. Inverting shock polarity reversed this effect.
Conclusion: ICD monophasic defibrillation shocks create large dynamically interacting areas of both negative and positive polarization.     

31P nuclear magnetic resonance study of the recovery characteristics of high energy phosphate compounds and intracellular pH after global ischaemia in the perfused guinea-pig heart

(1) The recovery of high energy phosphate compounds in perfused guinea-pig heart at 20°C after a 12 min period of global ischaemia was examined using ³¹P-NMR with a time resolution of 12 s. (2) This time resolution was achieved by overlaying the data acquired from five successive ischaemic periods by arresting and restoring the flow of perfusion fluid to the heart in synchrony with the data acquisition sequence. (3) The rate of creatine phosphate resynthesis after the ischaemic period proceeded 14 times faster than its rate of loss during the ischaemic period. ATP levels did not decrease during ischaemia and ADP was undetectable at any time. (4) Estimates of intracellular pH from the chemical shift of the inorganic phosphate peak were impossible in normal guinea-pigs since the inorganic phosphate peak was not clearly defined. (5) During the ischaemic period the inorganic phosphate peak increased in size and shifted upfield. On restoration of flow, the inorganic phosphate peak collapsed in a complex way following a different path to its formation during ischaemia.     

Reduction of atrial fibrillation inducibility by radiofrequency ablation: an experimental study

A study is made of the antifibrillatory effects of radiofrequency (RF)-induced atrial lesions using nine Langendorff-perfused rabbit hearts in which the atrial electrophysiological properties and atrial fibrillation (AF) inducibility were modified by atrial stretching. Using a multiple electrode consisting of 121 unipolar electrodes, determinations were made of the atrial refractory periods, conduction velocity, wavelength of the atrial activation process, and the inducibility of sustained AF episodes (duration over 30 s) by atrial burst pacing in four situations: (a) control; (b) following dilatation of the right atrium; (c) after adding an RF linear lesion at the cava-tricuspid annulus isthmus; and (d) after adding two RF linear lesions rounding the base of the right atrial appendage and extending from the inferior zone of the sulcus terminalis to the anterior wall of the appendage. Under control conditions, AF was not induced in any of the experiments. The wavelengths were 10.5 +/- 1.2 cm for basic cycles of 250 ms and 6.6 +/- 0.5 cm for cycles of 100 ms. Following dilatation, a significant decrease was recorded in the atrial refractory periods, conduction velocity, and wavelength, which reached values of 6.1 +/- 0.7 cm (250-ms cycle, P < 0.01), and 3.9 +/- 0.3 cm (100-ms cycle, P < 0.01); AF was induced in five cases (P < 0.05). After producing the lesion at the cava-tricuspid isthmus, the electrophysiological modifications induced by atrial dilatation persisted (wavelength = 6.2 +/- 0.6 cm (250-ms cycle) and 4.3 +/- 0.3 cm (100-ms cycle); P < 0.01 vs the control) and AF was triggered in eight cases (P < 0.0001). In turn, on adding the two lesions at the right atrial free wall and appendage, AF was induced only in one experiment (P = NS vs control), and the dilatation-induced decrease in refractoriness and wavelength was attenuated. Nevertheless, differences remained significant with respect to the controls, with the exception of the functional refractory periods determined at cycles of 100 ms. In this phase, the wavelength was 6.6 +/- 0.7 cm (250-ms cycle, P < 0.01 vs control) and 4.9 +/- 0.5 cm (100-ms cycle; P < 0.05). Atrial conduction between the zones separated by the lesions was blocked at any frequency, or selectively at rapid atrial activation frequencies. In conclusion: (a) the production of three linear lesions in the right atrium (cava-tricuspid isthmus, atrial appendage, and inferior free wall) reduces AF inducibility in the experimental model used; (b) conduction block (either absolute or frequency dependent) through the lesions, reduction in tissue mass caused by lesion creation, and possibly the attenuation of the shortening of atrial refractoriness and wavelength in the zones not separated by the lesions are implicated in the reduction of AF inducibility; and (c) the single lesion in the cava-tricuspid isthmus does not impede AF inducibility.     

31P Nuclear magnetic resonance measurement of cardiac pH in perfused guinea-pig hearts.

Cardiac pH was measured by ³¹P nuclear magnetic resonance spectroscopy. Measurements were made on 23 control hearts perfused with Krebs-Henseleit bicarbonate buffer containing potassium phosphate (1.2 mm) at pH 7.4, but with no external bathing medium. Only one very weak peak could be observed in the orthophosphate region at pH 7.0±0.1. Previous reports have shown a relatively strong line in this region at pH 7.4. The pH 7.0 value was confirmed by perfusion with Krebs-Henseleit bicarbonate-phosphate at pH 7.5, but this time in the presence of an external bathing medium composed of the same buffer. Two peaks were observed in the orthophosphate region. One was at pH 7.0 while the other was at pH 7.5. Replacement of the external bathing medium and perfusate by one free of phosphate (Krebs-Henseleit bicarbonate-Tris-HCl, 1.2 mm Tris plus 1.2 mm KCl, pH 7.4) caused the pH 7.5 peak to disappear but did not affect the pH 7.0 line. Thus, cardiac pH in well-oxygenated, Krebs-Henseleit bicarbonate-phosphate perfused hearts is 7.0, not 7.4. In addition, the magnitude of the observed acidosis associated with coronary artery ligation was about two times smaller (∼0.4 pH units) than that seen in the other studies owing to this difference in control pH. The current value of cardiac pH determined by nuclear magnetic resonance is now in excellent agreement with the values determined by more conventional methods.     

Absolute beat-to-beat variability and instability parameters of ECG intervals: biomarkers for predicting ischaemia-induced ventricular fibrillation

Background and Purpose

Predicting lethal arrhythmia liability from beat-to-beat variability and instability (BVI) of the ECG intervals is a useful technique in drug assessment. Most investigators use only arrhythmia-free ECGs for this. Recently, it was shown that drug-induced torsades de pointes (TdP) liability can be predicted more accurately from BVI measured irrespective of rhythm, even during arrhythmias (absolute BVI). The present study tested the broader applicability of this assessment by examining whether absolute BVI parameters predict another potential lethal arrhythmia, ischaemia-induced ventricular fibrillation (VF).

Experimental Approach

Langendorff-perfused rat hearts were subjected to regional ischaemia for 15 min. Absolute BVI parameters were derived from ECG intervals measured in 40 consecutive ventricular complexes (irrespective of rhythm) immediately preceding VF onset and compared with time-matched values in hearts not expressing VF.

Key Results

Increased frequency of non-sinus beats and ‘R on T’ arrhythmic beats, shortened mean RR and electrical diastolic intervals, and increased BVI of cycle length and repolarization predicted VF occurrence. Absolute BVI parameters that quantify variability of repolarization (e.g. ‘short-term variability’ of QT interval) had the best predictive power with high sensitivity and specificity. In contrast, VF was not predicted by any BVI parameter derived from the last arrhythmia-free interlude before VF.

Conclusions and Implications

The novel absolute BVI parameters that predicted TdP in rabbit also predict ischaemia-induced VF in rat, indicating a diagnostic and mechanistic congruence. Repolarization inhomogeneity represents a pivotal biomarker of ischaemia-induced VF. The newly validated biomarkers could serve as surrogates for VF in pre-clinical drug investigations.     

Excitation-dependent intracellular Ca2+ waves at the border zone of the cryo-injured rat heart revealed by real-time confocal microscopy

Intracellular Ca2+ waves, which develop under Ca2+-overloaded conditions of the injured myocardium, are regarded as an important substrate for triggered arrhythmias. However, little is known about whether Ca2+ waves arise or become proarrhythmic in the injured heart in situ. On the hypothesis that injured myocardium manifests frequent Ca2+ waves and produce an oscillatory [Ca2+]i rise leading to triggered activity, we applied cryo-injury to the epicardial surface of fluo 3-AM-loaded perfused rat hearts and analyzed spatiotemporal [Ca2+]i changes at border zones of the injured myocardium using real-time confocal microscopy. In intact regions Ca2+ waves barely emerged, whereas the border zone myocardium exhibited frequent Ca2+ waves, propagating randomly within the individual cells. Two different types of Ca2+ waves were identified: highly frequent waves (159.6+/-86.5 waves/min/cell, n=266) adjacent to the cryo-ablated regions, and less frequent waves (79.0+/-50.1 waves/min/cell, n=160) slightly farther (>2 cells) away from the ablated regions (vicinities). The former Ca2+ waves emerged asynchronously to Ca2+ transients. Contrariwise, the latter depended on ventricular excitation: they vanished instantaneously on Ca2+ transients, but emerged more frequently and propagated more swiftly after cessation of higher-frequency pacing. Immediately after 3-Hz pacing, some cryo-injured hearts exhibited oscillatory [Ca2+]i rises; an instantaneous and synchronous elevation of [Ca2+]i followed by burst occurrence of Ca2+ waves with a gradual decrease in incidence and propagation velocity in a considerable number of cells. These observations indicate that myocardial injury induces Ca2+ waves in the heart, and that their synchronous occurrence could become a substrate for triggered arrhythmias.