Kiyoshi Kawakubo

Assessment of the primary effect of aging on heart rate variability in humans

Beat-to-beat heart rate variability (HRV), reflecting cardiac autonomic control mechanisms, is known to change with age. However, the degree to which this change is mediated by aging per se or by physiologic changes characteristic of normative aging is still unclear. This study was designed to examine the association of aerobic fitness, body habitus or obesity, and blood pressure with age-related changes in HRV. Resting HRV data was recorded from 373 healthy subjects (124 men, 249 women; are range, 16–69 y) and analyzed by coarse-graining spectral analysis to decompose the total spectral power into its harmonic and fractal components. The low- and high-frequency (LF, 0.0–0.15 Hz; HF, >0.15 Hz) harmonic components were calculated from the former, whereas the latter was used to calculate the integrated power (FR) and the spectral exponent β, which were, in turn, used to evaluate the overall complexity of HRV. Factor analysis was performed to test whether potentially age-related changes in the components of HRV might be observed secondarily through other variables affecting HRV. Significant (p<0.05) age-related changes in the harmonic (HF and LF) and fractal (FR and β) components of HRV were generally consistent with those described in the literature. In addition, factor analysis showed that there was a unique common factor that primarily explained correlations among age, HF, and β (p<0.05) without the contributions from LF, FR, aerobic fitness, body habitus or obesity, and blood pressure. It was concluded that, in this population-based sample, age-related changes in HF and β, both of which reflect vagal modulation of heart rate, were primarily mediated by aging per se and not by physiologic changes characteristic of normative aging.

Left ventricular filling determined by Doppler echocardiography in diabetes mellitus

Abstract Diabetes mellitus is associated with a high mortality from cardiac disease attributed to coronary artery atherosclerosis or systemic hypertension. Increasing evidence indicates that cardiac dysfunction occurs even in diabetics with normal coronary arteries. 1–3 In 1972, Rubier et al 1 reported 4 adult-onset diabetic patients who had cardiomegaly and congestive heart failure in the absence of major coronary artery disease or hypertension. Hamby et al 2 observed a high incidence of diabetes mellitus in their series of patients with idiopathic cardiomyopathy. Furthermore, several investigators have shown that abnormalities of left ventricular (LV) diastolic function are common even in diabetics without clinical manifestations of congestive heart failure. 3–6 Whether these abnormalities result from a microangiopathic process in the heart or from metabolic abnormalities inherent to diabetes mellitus is still unclear. 7 Measurement of transmitral flow velocity by Doppler echocardiography has recently been shown to be useful in identifying abnormal LV diastolic filling properties in a variety of disease states. 8–11 This study evaluates the diastolic LV filling characteristics in patients with adult-onset diabetes mellitus using pulsed Doppler echocardiography.

Different recovery process of ST depression on postexercise electrocardiograms in women in standing and supine positions.

False-positive exercise test responses are frequently observed in women. To differentiate a false-positive from a true-positive test response, the effect of postures for recording a postexercise electrocardiogram to the recovery process of ST depression was investigated in 26 women with nonischemic ST depression and in 14 patients with typical angina pectoris. Exercise tests were performed twice, and the postexercise electrocardiogram was recorded while standing during the first test and in the supine position during the second test. In the false-positive test, maximal ST depression occurred immediately after exercise and showed a rapid recovery process in the early recovery phase. However, ST depression persisted without complete recovery, or increased in the late recovery phase as long as subjects were kept standing. In contrast, ST depression returned to the control level when subjects changed to the supine position after exercising. This discrepant pattern in the recovery process of ST depression by changing postures was not observed in the true-positive test results. Changing postures for recording postexercise electrocardiograms could be helpful in differentiating a false-positive response from a true ischemic response.

ST-T isointegral analysis of exercise stress body surface mapping for identifying ischemic areas in patients with angina pectoris

ST-T isointegral analysis of body surface mapping was used in an attempt to localize ischemic areas on exercise tests. In 28 patients with angina pectoris and 10 healthy subjects, body surface potential was recorded with 87 leads, and ST isopotential and ST-T isointegral maps were constructed. In all 10 healthy subjects, the basic pattern of the ST-T isointegral map showed no significant change after exercise. In 23 of 28 patients with angina pectoris (82%), alterations in the ST-T isointegral map after exercise were observed. They were divided into four types (anterior, inferoposterior, lateral, and global) according to the distribution of negative values, which were well correlated with the extent of ischemic area determined by thallium myocardial scintigraphy and coronary angiography. The postexercise ST-T isointegral map was normalized after administration of nitroglycerin in four of five patients. In five patients (18%) who did not show abnormalities on the postexercise ST-T isointegral map, the magnitude of maximal ST depression was significantly smaller than that observed in the other 23 patients with angina pectoris (0.14 vs 0.23 mV on the average, p less than 0.05). It was concluded that the exercise test with ST-T isointegral mapping is a new method for noninvasive detection of location and severity of ischemic regions.

Effects of Antiarrhythmic Drugs on the Repetitive Extrasystole Threshold and the Ventricular Fibrillation Threshold

The effects of class 1 antiarrhythmic drugs on the repetitive extrasystole threshold (RET) and the ventricular fibrillation threshold (VFT) were studied in 32 anesthetized dogs with localized transmural necrosis. All four drugs significantly increased VFT. Although lidocaine and mexiletine increased RET, procainamide and disopyramide did not. We conclude that class 1b antiarrhythmic agents prevent ventricular fibrillation by suppressing the initiation of reentry, and that class 1a drugs decrease the vulnerability by preventing the reentrant repetitive excitation from degenerating into chaotic multiple reentries.

Effects of Rapid Saline Infusion on Orthostatic Intolerance and Autonomic Tone After 20 Days Bed Rest

To test whether acute volume expansion can normalize orthostatic intolerance and autonomic tone after prolonged bed rest (BR), 23 men were subjected to 20 days BR. Left ventricular (LV) echocardiography was performed during the lower body negative pressure (LBNP) test before and after BR with and without preceding rapid infusion of saline (1,500 ml/30 min). Saline infusion restored heart rate, LV dimension, and stroke volume during LBNP, increased cardiac output (from 4.1 +/- 1 to 5.3 +/- 1 L/min), and normalized LBNP tolerance time (from 11 +/- 4 to 23 +/- 6 minutes). In 9 men, a Holter electrocardiogram was recorded on the day before BR, the fourth and twentieth days of BR, and the day after BR. The high-frequency component of heart rate variability during sleep gradually decreased and reached the lowest level on the day after BR (100%, 66 +/- 16%, 39 +/- 18%, 10 +/- 8%). Thus, restoring decreased blood volume is an effective countermeasure for orthostatic intolerance after BR. However, decreased vagal tone persisted, suggesting reset autonomic tone.

Epicardial mapping of polymorphous ventricular tachycardias induced in the canine heart with procainamide

To elucidate the mechanisms of the arrhythmogenic and antifibrillatory action of procainamide, 24 episodes of polymorphous ventricular tachycardia were analyzed. They were induced electrically in 12 canine hearts before and after the administration of 40 mg/kg of procainamide. The isochronal maps of the epicardial activation sequence were successfully constructed by 40 simultaneously recorded bipolar electrograms in 14 of 17 episodes after procainamide. The isochronal maps showed a possible macroreentrant circuit in 12 episodes, and in four of them the functional block was noticed to have disappeared before the termination of tachycardia. This study suggests that procainamide predisposes the ventricle to reentrant tachyarrhythmias and that the dimension of the reentrant circuit induced is too large to be fragmented into multiple reentries, which results in the prevention of the development of ventricular fibrillation.

Detecting Restenosis after Percutaneous Coronary Intervention Using Exercise-Stress Electrocardiogram Findings Including QT Dispersion

Despite the advent of drug‐eluting stents in Japan, bare metal stents or conventional balloon angioplasty are still indicated in some patients needing elective percutaneous coronary intervention (PCI) and in patients with acute coronary syndrome if these patients develop side effects while taking ticlopidine. In such patients, restenosis is a problem that is difficult to diagnose. To investigate the comparative diagnostic accuracy of the exercise‐stress electrocardiogram (ECG) for detecting restenosis after PCI, we measured conventional ST‐segment changes and QT dispersion during exercise‐stress testing in 173 patients with elective PCI (63 ± 10 years old). Exercise‐stress testing was performed 3 to 6 months after successful PCI, and restenosis was confirmed by follow‐up coronary angiogram. There were 98 patients with a prior myocardial infarction (prior MI group and 76 patients with no prior myocardial infarction (no MI group). Restenosis was found in 45 patients (46% in the prior MI group and 26 patients (34%) in the no MI group. Conventional ST‐segment depression (>1:0 mm, J 60 ms indicating exercise‐induced myocardial ischemia had a sensitivity of around 50% and a specificity of around 70% for diagnosing restenosis in both groups. In the prior MI group, QT dispersion was increased by exercise‐stress testing in both patients with and without restenosis, whereas in the no MI group, QT dispersion increased only in patients with restenosis. With a cut‐off value of >60 ms, QT dispersion had a sensitivity of 54% and a specificity of 68% for detecting restenosis in the no MI group; these values were comparable to those seen with conventional ST‐segment changes. In conclusion, due to its low cost, exercise‐stress ECG remains useful for diagnosing restenosis following PCI if the clinician understands its limited sensitivity and specificity. The presence of a prior MI must be considered when QT dispersion during exercise‐stress testing is used for detecting restenosis.

Prognostic Significance of Treadmill Exercise Stress Test in Diabetic Patients Without Cardiovascular Signs

As in the Western countries, the incidence of coronary artery disease in diabetic patients is increasing in Japan. Early detection of coronary artery disease is important in the management of diabetic patients. However, because painless myocardial infarction is frequent in diabetics(l), silent ischemia might be also frequent in asymptomatic diabetic patients. Exercise electrocardiography is useful in the early detection of coronary artery disease, but no data was available concerning the incidence and prognostic significance of exercise electrocardiographic abnormalities in asymptomatic diabetic patients in Japan. To identify incidence and prognostic significance of exercise-induced abnormalities in asymptomatic Type 2 diabetic patients, we performed treadmill exercise stress tests in 176 consecutive patients with no symptoms and signs suggestive of cardiac disease and they were followed prospectively.

Presence diagnosis and severity evaluation of coronary arteriosclerosis based on HR-ST loop during treadmil test.

運動負荷試験中から回復期にかけての心拍数 (横軸) とST下降度 (縦軸) の関係をHR-STループとして表わし, 冠動脈硬化症の重症度を推定することを試みた.対象は, トレッドミル負荷時に有意なST下降のみられた36例 (平均年齢54歳) であり, 有意狭窄無し (0VD) 12例, 1枝狭窄 (1VD) 13例, 2枝以上狭窄 (MVD) 11例であった.HR-STループはV5誘導についてML-8000 (フクダ電子) にて解析し, A型 (反時計方向回転) , C型 (時計方向回転) , B型 (A型とC型の中間) , C型 (C型でST下降の回復遅延を伴うもの) に分けられた.A型は9人の0VDと3人の1VDにみられ, B型は3人の0VDと6人の1VDに, C型は2人の1VDと5人のMVDに, C型は2人の1VDと6人のMVDにみられた.最大ST下降度には0VD, 1VD, MVDの間で差がみられなかった.HR-STループは偽陽性ST下降の鑑別と冠動脈硬化の重症度評価に有用であった.