Neurostimulatory and antioxidative effects of L-deprenyl in aged rat brain regions

This study investigated the influence of chronically administered L-deprenyl on normal ageing-related parameters: multiple unit action potentials, the activities of the enzymes Na⁺,K⁺-adenosinetriphosphatase, glutathione-s-transferase and glutathione peroxidase, and the levels of lipid peroxidation products and lipofuscin contents in the brain regions (cerebral cortex, hippocampus, striatum and thalamus) of 24-month-old rats. The drug increased the activity of Na⁺,K⁺-ATPase and glutathione-s-transferase. The activity of glutathione peroxidase remained unaffected. The drug also increased the multiple unit action potentials activity. The levels of lipid peroxidation products were, however, decreased, and lipofuscin accumulation was diminished by the drug. The results essentially indicated that chronic treatment of rats with L-deprenyl significantly influenced the ageing-related alterations in: multiple unit action potentials, Na⁺,K⁺-adenosinetriphosphatase, glutathione-s-transferase, lipid peroxidation products and lipofuscin accumulation. These novel data on the effect of L-deprenyl on parameters of normal ageing provide new additional evidence concerning the anti-ageing therapeutic potential of L-deprenyl. This revised version was published online in July 2006 with corrections to the Cover Date.     

Epinephrine-Induced Ventricular Premature Complexes Due to Early Afterdepolarizations and Effects of Verapamil and Propranolol in a Patient with Congenital Long QT Syndrome

Epinephrine-Induced VPCs and EADs in Congenital LQTS. We report a patient with congenital long QT syndrome in whom early afterdcpolarizations (RAl)s) were demonstrated on monophasic action potential (MAP) recordings in the left ventricular mid-base inferior wall. Epinephrine infusion at 5 fig/mm increased the amplitude of the EADs and the late component of the T(U) wave. Epinephrine also induced ventricular premature complexes (VPCs) with right hundle branch block morphology and left-axis deviation that occurred from the peak of the EADs. Verapamil injection (5 nig) during continuous epinephrine infusion abolished all VPCs with a slight reduction in the amplitude of the EADs. Propranolol injection (5 mg) in addition to verapamil further reduced the amplitude of the EADs and the late component of the T(U) wave. These findings suggest that the epinephrinc-induced VPCs were closely related to triggered rhythm arising from the EADs, and that both verapumil and propranoloi were effective for the suppression of VPCs and EADs.     

Bolus propulsive activity of the tongue in dysphagic cancer patients

Videofluoroscopic recordings were analyzed for liquid swallows in dysphagic patients with cancer involving the pharynx. Temporal measurements were made for the tongue stripping action in relation to velar and hyoid function. Dysphagic subjects as a group displayed an altered sequence of activity compared to normal controls, with the onset of stripping occurring after velar closure. Tongue stripping action and hyoid movement appeared to be time-locked to a greater extent than tongue stripping and velar closure. Duration of the stripping gesture was longer in dysphagic patients than in normal controls.     

Melatonin modulates the action of near infrared radiation on cell adhesion

The adhesion of human cervical cancer (HeLa) cells to a glass matrix is evaluated following their irradiation in a suspension with a pulsed near-infrared (IR) light-emitting diode (wavelength 820 nm, pulse repetition frequency 10 Hz, irradiation dose 16-120 J/m2) when melatonin (4 x 10(-11) to 4 x 10(-5) m) is added to cell suspension immediately before or after the irradiation. Also, the dependence of visible-to-near-IR radiation (600-840 nm, 52 J/m2) on cell adhesion (action spectrum) is recorded in absence and presence of melatonin (4 x 10(-6) m). It is found that melatonin in pharmacological concentrations (but not in physiological range) inhibited cell adherence. Irradiation of cells before or after melatonin treatment normalizes cell adhesion to control level. Melatonin in pharmacological concentrations eliminates stimulation of cell attachment induced by irradiation. Pre-treatment (but not post-treatment) with melatonin in the physiological concentration eliminates cell adhesion stimulation induced by irradiation. Melatonin modifies the light action spectrum significantly in near IR region (760-840 nm only). Thus, the peak at 820-830 nm characteristic for the light action spectrum is fully reduced.     

Electrophysiological effects of flecainide and sotalol in the human atrium during persistent atrial fibrillation

Aims Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. These changes promote persistence of AF. Pharmacological prolongation of atrial action potential duration (APD) may therefore help to prevent recurrent AF. In addition to prolonging APD, sodium channel blockers may prevent AF by inducing post–repolarization refractoriness (PRR). We studied whether two antiarrhythmic drugs (sotalol, flecainide) prolong APD or induce PRR in the fibrillating human atrium. Methods In 12 patients with persistent AF (11 male, 58 ± 5 yrs, 27 ± 7 months duration of AF), we recorded monophasic action potentials from the right atrial appendage and inferior right atrium at baseline and 15 minutes after intravenous administration of sotalol (1.5 mg/kg) or flecainide (2 mg/kg). APD and effective refractory periods (ERP) were determined. Results Both drugs prolonged APD90 during AF (flecainide from 109 ± 7 ms to 137 ± 10 ms, sotalol from 108 ± 6 ms to 131 ± 8 ms, both p < 0.05 vs. baseline). Sotalol prolonged ERP in parallel to APD (from 119 ± 8 ms to 139 ± 8 ms, p < 0.05). Flecainide induced PRR by prolonging ERP more than APD90 (from 134 ± 9 ms to 197 ± 28 ms, p < 0.05 vs. baseline and vs. sotalol). Conclusions Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans. In addition, flecainide induces atrial PRR. These electrophysiological effects may reduce AF recurrences and prevent their persistence.Drs. Kirchhof, Engelen and Breithardt are Members of the Kompetenznetz Vorhofflimmern     

Increased Dispersion of Repolarization Time Determined by Monophasic Action Potentials in Two Patients with Familial Idiopathic Ventricular Fibrillation

Increased Dispersion of RT in Familial Idiopathic VF. Introduction: The role of increased dispersion of repolarization in the genesis of torsades de pointes in patients with long QT syndrome has been clarified, but its role in the genesis of idiopathic ventricular fibrillation (VF) is not yet known. To investigate the pathogenesis of VF, we recorded monophasic action potentials (MAPs) from two siblings (48- and 36-year-old males) with familial idiopathic VF. Methods and Results: The elder brother (patient I) showed a late r’ wave in lead V¹ and ST segment elevation in leads V¹ through V³. The younger brother (patient 2) had late r’ waves and ST segment elevation in leads II, III, and aVF, and the configurations were very similar to those of patient I. MAPs were recorded from several sites in the right ventricular (RV) and left ventricular (LV) endocardium during constant right atrial pacing. The repolarization time (RT) was defined as the sum of the activation time (AT) and action potential duration (APD) at 90% repolarization. In patient 1, marked prolongation of the AT (140 msec) and the RT (380 msec) was recorded in the RV septum of the outflow tract, and the RT dispersion was markedly increased (125 msec). In contrast, patient 2 showed prolongation of the AT (80 msec) and RT (310 msec), and fractionated electrograms in the RV floor of the inflow tract. The RT dispersion was also increased (80 msec). VF and nonsustained polymorphic ventricular tachycardia were induced by double premature stimulation in patients 1 and 2, respectively. Chronic amiodarone therapy decreased the RT dispersion and suppressed the induction of ventricular tachyarrhythmias in patient 2, although late r’ waves and slight ST segment elevation were unmasked in leads V₁, and V₂. Conclusion: Our data suggest that the increased dispersion of the RT, which was due mainly to a localized conduction delay in the RV, created an arrhythmogenic substrate in the two patients with familial idiopathic VF.     

Effect of Strength and Timing of Transmembrane Current Pulses on Isolated Ventricular Myocytes

INTRODUCTION: Little is known about how the amplitude and timing of transmembrane current pulses affect transmembrane potential (Vm) and action potential duration (APD) in isolated myocytes. METHODS AND RESULTS: Ten ventricular myocytes were isolated from five rabbit hearts. Each cell was paced at an S1 cycle length of 250 msec, and S2 pulses of 10-msec duration were delivered at various strengths and time intervals. For all S2 strengths (0.2 to 1.5 nA), the magnitude of changes in Vm did not depend on polarity during the plateau, but were larger for depolarizing pulses during phase 3 repolarization. However, the magnitude of changes in APD varied with polarity during the entire action potential for strengths ranging from 0.5 to 1.5 nA. Greater changes in APD occurred for hyperpolarizing pulses during the plateau and depolarizing pulses during phase 3. In addition, we used a cardiac phase variable to quantify the current threshold for regenerative depolarization and repolarization as a function of prestimulus Vm. Regenerative depolarization occurred during phase 3 repolarization, and its current threshold was less than that required for regenerative repolarization that occurred during the plateau. These data were compared to computer simulations in a patch of membrane represented by Luo-Rudy dynamic kinetics, and the results were qualitatively similar, including the higher threshold for regenerative repolarization compared to regenerative depolarization. CONCLUSION: This characterization of the nonlinear response of isolated cells to transmembrane current, including phase resetting, should aid in understanding the mechanisms of defibrillation because shock-induced changes in Vm and APD have been implicated as important factors in determining defibrillation success.     

Potassium channels in cardiac cells

K⁺ channels in heart can be subdivided into two groups, voltage-operated and ligand-operated channels. Only the voltage-operated channels—i_K, i_to, and i_K1—and one ligand-operated channel—i_K(ACh)—are activated under physiological conditions; the i_K1 only carries large currents at the resting potential. The delayed K⁺ current, i_K, and the transient outward current, i_to, are important for the plateau and repolarization phase of the action potential, and thus affect the refractory period in atrial and ventricular cells and also the frequency in the sinoatrial node. A high density of i_to and i_Ca is responsible for the spike-dome appearance of the plateau phase in adult atrial cells, epicardial myocytes, and Purkinje cells stimulated by catecholamines. The action-potential duration in these cells is more sensitive to K_e ⁺, frequency, and drugs. The i_K(ACh) can also be activated by adenosine and somatostatin. Its density is high in nodal and atrial tissue. Under pathological conditions, K⁺ channels dependent on ATP, Na_i ⁺, and fatty acids are activated and can carry large currents at depolarized levels. Local changes in the concentration of ATP or Na close to the membrane are probably important for the activation process. The study of pharmacological modulation of K⁺ currents should include frequency effects for the voltage-activated channels.     

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。