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. (Heart 1998;79:493-496) Keywords: signal averaged ECG; f-QRS duration; circadian rhythm; heart rate variability Signal averaged electrocardiography (saECG) is a non-invasive method of detecting the substrate for malignant ventricular arrhythmias and is widely used to identify individuals at high risk for such arrhythmias and for sudden cardiac death. [1][2][3][4][5] Although the saECG has been assumed to measure fixed parameters, several studies have shown that these are altered by changes in factors such as heart rate and autonomic tone.6-8 Analysis of heart rate variability has been used to evaluate cardiac autonomic tone. 9-11Heart rate, heart rate variability, cardiac autonomic tone, and ventricular arrhythmias are known to have a circadian rhythm, [12][13][14][15][16] but information on the possibility of a circadian rhythm of the saECG and on the contribution of circadian fluctuations in autonomic function to the saECG is limited. We investigated whether the saECG has a circadian rhythm in healthy subjects and examined the relation between circadian fluctuations of the saECG and heart rate variability. Methods STUDY POPULATIONWe analysed 24 hour ECG recordings obtained in 44 healthy volunteers (28 men and 16 women, mean age (SD): 28.2 (3.3) years) in whom no abnormalities were detected by the medical history, physical examination, biochemical profile, 12 lead ECG, echocardiogram, or chest x ray. No subjects were on drug treatment. ANALYSIS OF 24 HOUR ECG RECORDINGSThe 24 hour ECG recordings were made with a three channel recorder (model 459, Del Mar Avionics, Irvine, California, USA) using bipolar leads X, Y, and Z. saECG analysisSignal averaging was performed on the data obtained from the first 500 seconds of every hour over the 24 hour period and filtered with a bidirectional filter at 40 to 250 Hz. The filtered leads were combined to form a vector as: √X 2 +Y 2 +Z 2 . The QRS onset and oVset were determined by a computer algorithm. The computer determined QRS oVset point w...

Our objective was to examine the autonomic influence on QT interval dispersion using the head-up tilt test in healthy subjects. RR and QT intervals, heart rate variability, and plasma norepinephrine concentration were measured in the supine position and tilting to 70 degrees for 20 minutes using a footboard support in 15 healthy male volunteers (mean age +/- SD: 28.0 +/- 4.5 years). The rate-corrected QT interval (QTc) was calculated using Bazett's formula, and QT and QTc dispersions were defined as the maximum minus minimum values for the QT and QTc, respectively, from the 12-lead ECG. Spectral analysis of the heart rate variability generated values for the low- and high-frequency powers (LF and HF) and their ratio (LF/HF). Compared with values obtained in the supine position, tilting significantly increased QT (P < 0.05) and QTc dispersion (P < 0.01), the LF/HF ratio (P < 0.0001), and plasma norepinephrine concentration (P < 0.0001), and significantly decreased HF (P < 0.0001). QTc dispersion was positively correlated with the LF/HF ratio and plasma norepinephrine concentration, and negatively correlated with HF. These results suggest that head-up tilt testing increases QT dispersion by increasing sympathetic tone and/or decreasing vagal tone in healthy subjects.

Previously we have reported that in the rabbit the sinus node impulse spreads not only to the atrial muscle but also to the musculature in the venae cavae proximal to the heart10, 19). On the basis of this result, Mashiba and coworkers have introduced into electrophysiology the concept of sinocaval conduction. Recently ARITA and coworkers reported on the mechanical activity of the vena caval muscle of the rabbito. Further studies on the sinocaval conduction of the rabbit have revealed that the transmission of the sinus node impulse to the superior venae cavae is delayed during passage through three different sites: one is the sinus node and the others are the junctions of right and left superior venae cavae with the right atrium. These junctional areas have been found to take over the function of impulse initiation under certain conditions. We have called them the sinocaval (SC) areas. The present paper mainly deals with the functional properties of the SC areas. METHODSThe experimental methods employed here were the same as described prey iouslylo. RESULTS

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Background —Although bradykinin is thought to contribute to the effects of ACE inhibitors on the cardiovascular system, its precise role remains to be elucidated. Evidence suggests that bradykinin might be important in the upregulation of β-adrenergic receptors (β-ARs) induced by ACE inhibitors, and the role of bradykinin in this effect has now been investigated with cultured neonatal rat cardiac myocytes. Methods and Results —The density of β-ARs on the myocyte surface was determined with a binding assay with [ 3 H]CGP-12177. Incubation of cultured myocytes for 24 hours with the ACE inhibitor captopril (1 μmol/L) increased β-AR density by 35% and enhanced the response of cells to isoproterenol but not to forskolin. Neither an angiotensin-II type 1 (AT 1 ) receptor antagonist, CV-11974, nor angiotensin-I affected β-AR density. However, the bradykinin B 2 receptor antagonist Hoe 140 abolished the effect of captopril on β-AR upregulation in a dose-dependent manner. The protein kinase C inhibitor staurosporine (20 nmol/L) but neither indomethacin nor L-NAME also inhibited captopril-induced upregulation of β-ARs. Exogenous bradykinin increased the spontaneous beating frequency of cultured myocytes and Hoe 140 abolished this effect. Bradykinin level in the medium increased 1.4-fold by the treatment of cultured myocytes with captopril for 24 hours. Conclusions —The results suggest that captopril enhances β-AR responsiveness by inducing β-AR upregulation and that the latter effect is mediated by activation of bradykinin B 2 receptors and protein kinase C. These observations also offer insight into the different roles of ACE inhibitors and AT 1 receptor antagonists in the treatment of heart failure.

Nicorandil suppresses the early afterdepolarisations and ventricular tachyarrhythmias induced by Cs, possibly by increasing the membrane K conductance.

Background-Although tachycardia is commonly present in patients with congestive heart failure, its role in the development of congestive heart failure remains unclear. We studied the effect of rapid electrical stimulation of contraction on ␤-adrenergic receptor (␤-AR) signal pathway in cultured cardiomyocytes of neonatal rats. Methods and Results-Contraction of cardiomyocytes was induced by electrical stimulation at 50 V with twice the threshold pulse width. ␤-ARs were identified by [ 3 H]CGP-12177 and [ 3 H]dihydroalprenolol. Electrical stimulation reduced cell-surface but not total ␤-AR density; the effect was dependent on pacing frequency (a reduction of 11%, 28%, and 18% in cells paced at 2.5, 3.0, and 3.3 Hz, respectively). This reduction was apparent at 3 hours, in contrast to reduced ␤-AR density after exposure to isoproterenol (ISP) for 1 hour. The fraction and inhibition constant of ␤-AR binding agonist with high affinity were not affected by rapid electrical stimulation. In cardiomyocytes paced at 3.0 Hz for 24 hours, the response to ISP decreased compared with unpaced cells, 142% versus 204% of baseline with 1 mol/L ISP, whereas the responses to forskolin or acetylcholine were not different. Treatment of cardiomyocytes with 2,3-butanedione monoxime (10 mmol/L) or taxol (10 mol/L) inhibited the rapid pacing-induced reduction in ␤-AR density. Conclusions-Our results suggest that contractile activity is involved in regulation of cardiac function by modulating the ␤-AR system independently of hemodynamic and neurohormonal factors. This may help to elucidate the role of mechanical stress in the development of heart failure.

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