Hiroshi Ijiri

Circadian rhythm of autonomic nervous function in patients with normal-tension glaucoma compared with normal subjects using ambulatory electrocardiography

Purpose: To compare circadian rhythm of autonomic nervous function in patients with normal‐tension glaucoma with subjects with normal eyes. Methods: Thirty‐two patients with normal‐tension glaucoma and 32 age‐matched normal subjects who had no history of systemic disorders and no currently treated systemic disorders, especially diseases of the autonomic nervous system, were studied. An ambulatory electrocardiogram was installed that recorded heartbeats for 48 hours. Low‐frequency and high‐frequency values were calculated as markers of the autonomic nervous system status based on heart‐rate variability using a power‐spectrum analysis. Results: The low‐frequency values of patients with normal‐tension glaucoma during the spans of an active day and a resting night were significantly greater than those of normal subjects, and this difference was emphasized during the night resting span. However, the high‐frequency values of patients with normal‐tension glaucoma were similar to those of normal subjects. The normal subjects showed a significant agerelated decrease in all investigated parameters except the low‐frequency values during the resting span. However, the patients with normal‐tension glaucoma showed a significant age‐related decrease only in low‐frequency values during the active day. Patients with normal‐tension glaucoma with progressive visual field defects showed much greater values than other cases, although the values were not significantly different. Conclusion: These results indicate that a disturbance of the circadian rhythm of the autonomic nervous system may exist in patients with normal‐tension glaucoma.

Administration-time-dependent effects of diltiazem on the 24-hour blood pressure profile of essential hypertension patients

The aim of this study was to identify differences in the patterns of efficacy and duration of effect by diltiazem given in different dosage forms and schedules. Blood pressure (BP) and heart rate (HR) were monitored before and after treatment by ambulatory blood pressure monitoring for 48 h every 30 min. Patients were divided for treatment assignment into 4 groups -nocturnal BP dippers and nondippers. In dipper hypertension, diltiazem-retard at 08:00 (n = 7) had the most marked antihypertensive effects during nighttime rest (SBP; 136 +/- 14/118 +/- 9 mmHg, p < 0.01 before vs. after treatment). Diltiazem-retard at 19:00 (n = 6) exerted greatest effect during daytime activity (152 +/- 7/139 +/- 6, p < 0.01) with inhibition of the morning BP rise. Diltiazem (t.i.d., n = 5) had the best effect during daytime activity (151 +/- 16/136 +/- 9, p < 0.05). However, in nondipper hypertensive patients, diltiazem (t.i.d., n = 8) had the most pronounced antihypertensive effects during nightly rest (144 +/- 12/127 +/- 12, p < 0.05). Evening medication with diltiazem retard appears to be more efficacious than the other dosage schedules.

QT Dispersion in Dipper- and Nondipper-Type Hypertension

The aim of this study was to identify the relationship of QT dispersion on 12-lead electrocardiograms and left ventricular mass index on echocardiograms associated with the circadian rhythm of blood pressure (BP). Heart rate and BP were monitored every 30 min for 48 h in 62 patients with essential hypertension using an ambulatory BP monitoring device. The patients were divided into four groups according to gender and circadian BP pattern (nocturnal BP dipper or nondipper). The patients were classified as dippers if their daytime BP decreased by at least 10% during the night and all the other subjects were classified as nondippers. Age, body mass index, and 48-h mean BP were similar among the four groups. During the night-rest period, the systolic and diastolic BP were significantly decreased in dipper-type hypertensives. The maximum QTc interval and QTc dispersion were longer in nondippers than in dippers. Left ventricular mass index (LVMI) had a tendency to increase in nondippers. The nocturnal reduction of BP significantly correlated with QTc dispersion and LVMI. The QTc dispersion significantly correlated with LVMI and interventricular septum thickness.

Effect of imidapril in dipper and nondipper hypertensive patients: comparison between morning and evening administration.

The purpose of the study was to identify differences in the patterns of efficacy and duration of effects of imidapril administered at different times of the day (morning versus evening) in dipper and nondipper hypertensive patients. Twenty patients with untreated hypertension were classified into two groups: dippers (n = 9) and nondippers (n = 11). Imidapril (10 mg) was given at 07:00 or 18:00 for 4 weeks in a crossover fashion. Blood pressure (BP) and heart rate (HR) were monitored before and after morning and evening treatment every 30 min for 48h by ambulatory BP monitoring (ABPM). In dipper hypertension, the mean 48h BP was reduced with both doses. The decrease in the diurnal BP was stronger when the drug was administered in the evening than morning, but without significant difference. In nondipper hypertension, the systolic BP decreased at night with both doses, but the extent of the nocturnal reduction in systolic BP was greater after morning therapy. There were no significant differences in the decrease in BP during the day or night between the morning and evening administrations. When imidapril was administered in the morning, its serum concentration reached a maximum at 16:00, and when the drug was administered in the evening, it reached a maximum at 6:00. In dipper hypertension, the time taken for the blood concentration of imidapril to reach a maximum changed depending on its time of administration, and the time when the maximum antihypertensive effect of the drug appeared was different. In nondipper hypertension, decreases in the BP were confirmed at night regardless of the time of administration; this might be caused by angiotensin converting enzyme (ACE) inhibitors effectively blocking the BP from increasing by activating the parasympathetic nervous system. Therefore, when assessing the effectiveness of antihypertensive agents, factors such as the various patterns of BP before therapy and administration time must be considered. (Chronobiology International, 17(2), 209–219, 2000)

The Inhibitory Effects of Carvedilol Against Arrhythmias Induced by Coronary Reperfusion in Anesthetized Rats

Background: Previous study has shown the antiarrhythmic effects of carvedilol on isolated rat hearts, but little is known about the mechanism of this protective action. This article examines the inhibitory effect of carvedilol against arrhythmias induced by reperfusion in anesthetized rats. In addition, the results are compared with those with propranolol, super oxide dismutase (SOD) plus catalase, and a combination of both in order to elucidate the mechanism of the protective actions. Methods and Materials: Ninety percent of the rats in the control group showed lethal ventricular fibrillation (VF). Carvedilol at the doses of 0.03, 0.1, and 0.3 mg/kg significantly reduced the incidence of lethal VF to 0%, 0%, and 10%, respectively ( P < .05). In contrast, propranolol at the doses of 0.3, 1.0, and 3.0 mg/kg and SOD (35,000 units/kg) plus catalase (400,000 units/kg) did not reduce the incidence of lethal VF (80%, 60%, 70%, and 70%, respectively). However, administration of a combination of propranolol (1.0 mg/kg) and SOD plus catalase completely inhibited the occurrence of lethal VF to 0% ( P < .05). Conclusion: These results indicate that carvedilol has the inhibitory effect against reperfusion arrhythmias in rats and suggest that the mechanism of action of this compound is related to the combined effects of beta-blocking and antioxidant.

What time is the "biologic zero hour" of circadian variability?

Most ambulatory blood pressure monitoring (ABPM) studies have used a mechanical clock as the reference time, but there is no biologic background for assuming that midnight by the mechanical clock is zero hour by the biologic clock. The aim of this study was to determine the biologic zero hour as the zero reference time by evaluating the circadian rhythm of blood pressure, heart rate, and activity. Twenty healthy medical students (18 men, 2 women, mean age 26 years old) were recruited and blood pressure, heart rate, and physical activity were monitored simultaneously by an ABPM device every 30 min for 48 h. Four concepts of zero time were selected in this study and analyzed regarding biologic zero hour: 24:00 by the mechanical clock (clock time); the time of awakening, based on a diary (diary time); the time of a sudden increment in physical activity in the morning (activity time); and the middle of the total sleeping time, based on the diary (midsleeping time). The awakening time is a better individual index than the mechanical clock, and the midsleeping time as the zero reference point is better than the awakening time. We assessed the reproducibility of the data regarding the circadian troughs between the first and second day. The reproducibility of the day-to-day variation of the blood pressure and heart rate was poor. The reproducibility of physical activity was fairly good, but the magnitude of activity was small. A 48-h monitoring profile is superior to a 24-h monitoring period.

Relation between QT interval dispersion and heart rate.

Because the relation between QT dispersion (QTd) and heart rate (HR) are different from that between QT interval and HR, QTd could be overadjusted at a high HR and be underadjusted at a slow HR if we use Bazetts formula to adjust QTd. HR adjustment of QTd is not needed to evaluate repolarization dispersion.

Effects of bidisomide (SC-40230), a new class I antiarrhythmic agent, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats; comparison with mexiletine and disopyramide

SummaryWe investigated the antiarrhythmic effects of bidisomide (SC-40230), a new class I antiarrhythmic drug, in early-phase ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats. The effects of bidisomide were compared with those of mexiletine (MXT) and disopyramide (DSP), established class I antiarrhythmic drugs. Drugs were administered intravenously, 5 min before induction of coronary occlusion. Bidisomide (5 mg/kg) reduced the number of premature ventricular complexes and the incidence of ventricular tachycardia and ventricular fibrillation similarly to MXT and DSP in rats with ventricular arrhythmias induced by coronary artery occlusion. In rats with ventricular arrhythmias induced by coronary artery reperfusion following a 5min coronary occlusion, the antiarrhythmic effects of 5 mg/kg of bidisomide were similar to those of the same doses of MXT and DSP. All three drugs significantly slowed the heart rate. Our results suggest that bidisomide may effectively reduce the severity of lifethreatening ventricular arrhythmias that occur during acute coronary syndrome.

Restored atrial excitability after late recanalization in a patient with atrial standstill and acute myocardial infarction.

KOSHIMIZU, T‐A., et al.: Restored Atrial Excitability After Late Recanalization in a Patient with Atrial Standstill and Acute Myocardial Infarction. Atrial standstill is electrophysiologically characterized by the loss of spontaneous excitation in atrial muscle and the inability to cause action potential firing upon electrical stimulation. Clinical diagnosis of transient standstill of the right atrium was made in a patient with acute occlusion of the right coronary artery and acute renal failure. Percutaneous coronary intervention, performed 5 days after the onset, restored the coronary blood flow and resulted in full recovery of electrical activity and regular sinus rhythm.

Improvement of exercise tolerance by single lead VDD pacemaker: evaluation using cardiopulmonary exercise test.

We used a Cardiopulmonary test to assess the physiological benefit of single lead VDD pacing in ten patients (six men, four women; aged 32–84 years, mean 69 years) with atrioventricular block. Maximal symptom‐limited treadmill exercise test using a ramp protocol was performed under VDD and VVIR or VVI pacing (VVI) in random sequence. The pacemaker was then programmed to the VDD mode, and Holter ECG was recorded in nine patients. Compared with findings during the VVI, the VDD mode had a greater chronotropic response (mean maximal heart rate, VDD 106 ± 17 beats/mm vs VVI 79 ± 19 beats/min, P = 0.03), and was associated with prolongation of exercise duration (VDD 11.2 ± 2.9 minute vs VVI 10.5 ± 3.1 minute; P = 0.01), and the onset of anaerobic threshold at a higher oxygen uptake (VDD 12.4 ± 3.4 mL/min per kilogram vs WI 10.0 ± 2.1 mL/min per kilogram; P < 0.01). Atriai sensing was recognized in almost all normal sinus P waves for all cases examined using Holter ECG. Thus, chronotropic response during exercise by VDD pacemaker improved exercise tolerance, indicating that a VDD pacemaker might be useful for patients requiring physical activity.