Takehiko Fujino

Circadian rhythm of the signal averaged electrocardiogram and its relation to heart rate variability in healthy subjects

Objective To examine the circadian variation in the signal averaged electrocardiogram (saECG) and heart rate variability and investigate their relations in healthy subjects. Methods 24 hour ECGs were obtained with a three channel recorder using bipolar X, Y, and Z leads in 20 healthy subjects. The following variables were determined hourly: heart rate, filtered QRS (f-QRS) duration, low and high frequency components of heart rate variability (LF and HF), and the LF/HF ratio. Results Heart rate, f-QRS duration, HF, and the LF/HF ratio showed significant circadian rhythms, as determined by the single cosinor method. Heart rate and the LF/HF ratio increased during daytime, and f-QRS duration and HF increased at night. f-QRS duration was negatively correlated with heart rate (r = 0.95, p < 0.001) and the LF/HF ratio (r = 0.94, p < 0.001) and positively with HF (r = 0.93, p < 0.001). Conclusions f-QRS duration has a significant circadian rhythm in healthy subjects and is closely related to the circadian rhythm of autonomic tone.

Anti-inflammatory/anti-amyloidogenic effects of plasmalogens in lipopolysaccharide-induced neuroinflammation in adult mice

BackgroundNeuroinflammation involves the activation of glial cells in neurodegenerative diseases such as Alzheimer’s disease (AD). Plasmalogens (Pls) are glycerophospholipids constituting cellular membranes and play significant roles in membrane fluidity and cellular processes such as vesicular fusion and signal transduction.MethodsIn this study the preventive effects of Pls on systemic lipopolysaccharide (LPS)-induced neuroinflammation were investigated using immunohistochemistry, real-time PCR methods and analysis of brain glycerophospholipid levels in adult mice.ResultsIntraperitoneal (i.p.) injections of LPS (250 μg/kg) for seven days resulted in increases in the number of Iba-1-positive microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes in the prefrontal cortex (PFC) and hippocampus accompanied by the enhanced expression of IL-1β and TNF-α mRNAs. In addition, β-amyloid (Aβ3–16)-positive neurons appeared in the PFC and hippocampus of LPS-injected animals. The co-administration of Pls (i.p., 20 mg/kg) after daily LPS injections significantly attenuated both the activation of glial cells and the accumulation of Aβ proteins. Finally, the amount of Pls in the PFC and hippocampus decreased following the LPS injections and this reduction was suppressed by co-treatment with Pls.ConclusionsThese findings suggest that Pls have anti-neuroinflammatory and anti-amyloidogenic effects, thereby indicating the preventive or therapeutic application of Pls against AD.

Effects of vagal stimulation on cesium-induced early afterdepolarizations and ventricular arrhythmias in rabbits.

BackgroundPrevious evidence has shown that increased sympathetic tone enhances the cesium chloride (Cs)-induced early afterdepolarizations (EADs) and ventricular tachycardias (VTs). Methods and ResultsWe assessed the effects of vagal stimulation on Cs-induced EADs and ventricular arrhythmias in the rabbit heart. Monophasic action potentials (MAPs) of the left ventricular endocardium were recorded simultaneously with surface ECG. Two protocols were used: 1) While in their intrinsic sinus rhythm, 11 rabbits were given three intravenous Cs injections (1 mM/kg) 20 minutes apart, and the effects of vagal stimulation on the ventricular arrhythmias thus induced were examined. 2) Under constant atrial pacing (cycle length, 250 msec), EAD amplitude was measured after Cs injection (1 mM/kg) without (five rabbits, control group) or with (four rabbits, vagal stimulation group) vagal stimulation. We observed the following. 1) Cs produced EADs and VTs of polymorphic (PVT) and monomorphic (MVT) types. During PVT, the take-off potential of repetitive premature action potentials in MAP recordings was about the same as the peak level of EADs, and during MVT, the take-off potential was the level of full repolarization. Vagal stimulation suppressed PVT but not MVT. Vagal stimulation after spontaneous termination ofMVT restarted MVT of the same morphology at a rate much slower than the preceding sinus rate. 2) EAD amplitude was significantly smaller in the vagal stimulation group than in the control group. ConclusionsThe results suggest that PVT originated from triggering by EADs, whereas MVT was of different origin, and that vagal stimulation suppressed PVT by decreasing the amplitude of EADs.

Quantitative correlation between cardiovascular and plasma epinephrine response to mental stress

SummaryTo investigate the quantitative correlations between cardiovascular and endogenous catecholamine response to mental stress, we gave a mental arithmetic test to 20 young healthy men. A direct and non-invasive haemodynamic measurement was performed by serial M-mode echocardiography. Heart rate, blood pressure, cardiac output, stroke volume, ejection fraction, left ventricular end-systolic pressure-volume ratio and plasma epinephrine increased over the baseline period during the test. The peripheral resistance and left ventricular end-systolic volume decreased, whereas left ventricular end-diastolic volume and plasma norepinephrine were unaltered. Furthermore, the degree of change in each haemodynamic parameter showing significant reaction, was well correlated with that of the increase in plasma epinephrine. The data suggest that acute mental stress induces endogenous epinephrine secretion resulting in aβ-adrenergic activated state in the cardiovascular system, namely, positive chronotropism, positive inotropism and vasodilatation.

Effects of oral diltiazem on ventricular premature contractions.

The effects of oral diltiazem (90-180 mg/day for four weeks) on ventricular premature contractions (VPCs) were studied in 16 patients with frequent VPCs using 24-hour ambulatory ECG recordings. VPC frequency was evaluated as a function of underlying heart rate. Plots of VPC frequency vs. heart rate were made at 1-beat/min intervals for all heart rates recorded for at least five minutes during 24 hours. Patterns of correlation between VPC frequency and heart rate observed before diltiazem therapy included: 1) a relatively linear increase in VPCs with heart rate (positive correlation) in ten patients, 2) a linear decrease (negative correlation) in one patient, and 3) an increase at low heart rates and a decrease at high heart rates (bidirectional correlation) in five patients. Diltiazem significantly reduced the mean VPC frequency per 24 hours for patients with a positive correlation, but induced no significant change for patients with a negative or a bidirectional correlation. At the 65% level of VPC reduction, diltiazem was effective in eight of ten patients with a positive correlation but was not effective in the six patients with other correlations (p less than 0.01). These results suggest that an evaluation of VPC frequency as a function of heart rate predicts the response of VPCs to diltiazem.

Frequency of valvular regurgitation by color Doppler echocardiography in systemic lupus erythematosus

Abstract We studied valvular regurgitation in patients with systemic lupus erythematosus (SLE) by color Doppler echocardiography. Because valvular regurgitation occurs frequently in normal subjects, 1,2 we matched the patients by age with a control group. Furthermore, the same person examined both patients and normal subjects using the same Doppler echocardiographic apparatus.

Simultaneous preparation of purified plasmalogens and sphingomyelin in human erythrocytes with phospholipase A1 from Aspergillus orizae.

A method for the simultaneous purification of plasmalogens and sphingomyelin (SM) in human erythrocytes is described. Treatment of total lipids with n-hexane/acetone (1:1 v/v) resulted in selective precipitation of SM. Both the supernatant and the precipitate fractions were incubated with a phospholipase A1 (PLA1) from Aspergillus orizae for 3.5 h. The PLA1-treated lipids were extracted with n-hexane/isopropanol, the hexane layer was obtained using a Na2SO4 solution, and the hexane layer was further washed with water. At this step, the relative concentration of the plasmalogens was 92% of the total phospholipids in the supernatant fraction, and that of SM was 97.7% in the precipitate fraction. Each fraction was applied to high performance liquid chromatography (HPLC) for further purification. The plasmalogen and SM obtained were almost free of the other lipids. The purity of the plasmalogens and SM was monitored by HPLC, which can separate intact plasmalogens from their diacyl analogs.

Changes in Phospholipid Composition of Erythrocyte Membrane in Alzheimer's Disease

Background: There are several reports indicating a decrease of ethanolamine plasmalogen (pl-PE) in brain tissues and in serum of patients with Alzheimer’s disease (AD). The present study aimed to examine the composition of erythrocyte phospholipids including pl-PE in patients with AD. Method: A high-performance liquid chromatography (HPLC) method that can separate intact plasmalogens and all other phospholipid classes by a single chromatographic run was used. Results: The ratios of pl-PE, phosphatidylethanolamine (PE) and phosphatidylserine (PS) to sphingomyelin were low as compared to those of the age-matched controls. Conclusion: These changes in erythrocyte phospholipids may reflect changes induced by oxidative stress, indicating the presence of high oxidative stress in the peripheral blood of AD patients.

Relation between QT and RR intervals in patients with bradyarrhythmias.

OBJECTIVE--To investigate the relation between QT and RR intervals in the sick sinus syndrome or high degree atrioventricular block. PATIENTS--32 patients with episodes of prolonged RR intervals (> or = 2.6 s) on Holter electrocardiographic recordings. DESIGN--QT and RR intervals were measured manually every 100 to 150 beats on electrocardiographic strips reprinted from the Holter tape over 24 hours. The slope of the QT/RR relation was determined by the linear regression equation for RR intervals < or = 1.4 s (slope 1) and > 1.4 s (slope 2). RESULTS--Slope 2 (0.0068 (0.0030)) was significantly lower than slope 1 (0.0824 (0.0059), P < 0.0001) in the overall patient population. Slopes 1 and 2 were significantly lower (P < 0.001) in the 23 patients with QT intervals at the preceding RR interval of 1 s (QT1s) of < 0.44 s (0.0692 (0.0053) and 0.0019 (0.0030), respectively) than in the nine patients with QT1s intervals > or = 0.44 s (0.1159 (0.0091) and 0.0194 (0.0055), respectively). Slopes 1 and 2 correlated positively with QT1s interval in all patients. CONCLUSIONS--The QT/RR relation was comparatively flat when the RR interval was prolonged. Patients with prolonged QT intervals showed exaggerated prolongation of the QT interval with prolonged cycle lengths when compared with patients with normal QT intervals.

Effects of plasmalogens on systemic lipopolysaccharide-induced glial activation and β-amyloid accumulation in adult mice

Neuroinflammation essentially involves an activation of glial cells as the cause/effect of neurodegenerative diseases such as Alzheimers disease (AD). Plasmalogens (Pls) are glycerophospholipids constituting cellular membranes and play significant roles in membrane fluidity and cellular processes like vesicular fusion and signal transduction. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 250 μg/kg) for 7 days resulted in the morphological changes and increase in number of Iba‐1+ microglia showing neuroinflammation in the adult mouse hippocampus. The LPS‐induced activation of glial cells was significantly attenuated by i.p. pretreatment with Pls dissolved in corn oil. In addition, systemic injection of LPS induced Aβ1–16+ neurons in the hippocampus were also abolished by application of Pls. Finally, contents of Pls in the hippocampus decreased after LPS injection, and the reduction was suppressed by administration of Pls. These findings suggest an antiamyloidogenic effect of Pls, implicating a possible therapeutic application of Pls against AD.