Chiharu Ibukiyama

Assessment of Vasoactive Agents and Vascular Aging by the Second Derivative of Photoplethysmogram Waveform

To evaluate the clinical application of the second derivative of the fingertip photoplethysmogram waveform, we performed drug administration studies (study 1) and epidemiological studies (study 2). In study 1, ascending aortic pressure was recorded simultaneously with the fingertip photoplethysmogram and its second derivative in 39 patients with a mean+/-SD age of 54+/-11 years. The augmentation index was defined as the ratio of the height of the late systolic peak to that of the early systolic peak in the pulse. The second derivative consists of an a, b, c, and d wave in systole and an e wave in diastole. Ascending aortic pressure increased after injection of 2.5 microg angiotensin from 126/74 to 160/91 mm Hg and decreased after 0.3 mg sublingual nitroglycerin to 111/73 mm Hg. The d/a, the ratio of the height of the d wave to that of the a wave, decreased after angiotensin from -0.40+/-0.13 to -0.62+/-0.19 and increased after nitroglycerin to -0.25+/-0.12 (P<0.001 and P<0.001, respectively). The negative d/a increased with increases in plethysmographic and ascending aortic augmentation indices (r=0.79, P<0.001, and r=0.80, P<0.001, respectively). The negative d/a reflects the late systolic pressure augmentation in the ascending aorta and may be useful for noninvasive evaluation of the effects of vasoactive agents. In study 2, the second derivative of the plethysmogram waveform was measured in a total of 600 subjects (50 men and 50 women in each decade from the 3rd to the 8th) in our health assessment center. The b/a ratio increased with age, and c/a, d/a, and e/a ratios decreased with age. Thus, the second derivative aging index was defined as b-c-d-e/a. The second derivative wave aging index (y) increased with age (x) (r=0.80, P<0.001, y=0.023x-1.515). The second derivative aging index was higher in 126 subjects with any history of diabetes mellitus, hypertension, hypercholesterolemia, and ischemic heart disease than in age-matched subjects without such a history (-0.06+/-0.36 versus -0.22+/-0.41, P<0.01). Women had a higher aging index than men (P<0.01). The b-c-d-e/a ratio may be useful for evaluation of vascular aging and for screening of arteriosclerotic disease.

Underestimation of Vasodilator Effects of Nitroglycerin by Upper Limb Blood Pressure

To determine why upper limb blood pressure measurement underestimates the vasodilator effects of nitroglycerin on lowering ascending aortic systolic pressure, we studied 24 patients (58 +/- 11 years, mean +/- SD). Ascending aortic pressure and radial artery pulse calibrated by cuff blood pressure measurement at the brachial artery were recorded simultaneously before and 5 minutes after sublingual administration of 0.3 mg nitroglycerin. Waves were analyzed by a signal processor, and the fourth derivative wave was used to find the early (S1) and late (S2) systolic shoulders (S1 corresponds to the second zero crossing and S2 to the third zero crossing). Before nitroglycerin administration, maximal systolic pressure in the ascending aorta (141 +/- 21 mm Hg) coincided with the late systolic peak in all patients, and in most patients (21 of 24) maximal systolic pressure in the radial artery (140 +/- 19 mm Hg) coincided with the early systolic peak. Maximal systolic pressure decreased more in the ascending aorta than in the radial artery (22 +/- 13 and 11 +/- 11 mm Hg, respectively; P < .001). However, the reduction in the shoulder of late systolic pressure in the radial artery (24 +/- 13 mm Hg) clearly indicated the reduction in maximal systolic pressure (late systolic peak) in the ascending aorta. The augmentation index of the ratio of the height of late systolic pressure to early systolic pressure fell proportionally (r = .74, P < .001) in the radial artery (from 0.88 +/- 0.13 to 0.60 +/- 0.11) and in the ascending aorta (from 1.57 +/- 0.25 to 1.26 +/- 0.24), which indicated the reduction in late systolic pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

The beneficial effects of atrial natriuretic peptide on arrhythmias and myocardial high-energy phosphates after reperfusion

OBJECTIVES The aim of this investigation was to test whether the administration of atrial natriuretic peptide (ANP) has cardioprotective effects against ischaemic and reperfusion injury. METHODS Thoracotomized dogs underwent a 30 min left circumflex coronary artery occlusion and 60 min of reperfusion (control group; n = 16). The ANP group (n = 9) received a 20 micrograms bolus injection of synthetic alpha human ANP (SUN 4936) followed by infusion at a dose of 0.1 microgram/kg/min from the beginning of coronary occlusion to the end of the procedure. RESULTS Administration of exogenous ANP increased plasma ANP immediately and maintained levels at 3000 pg/ml, resulting in an 8-fold increase in plasma cyclic guanosine monophosphate (cGMP) levels. Plasma ANP and plasma cGMP levels did not change at all in controls. There were no significant differences in haemodynamic parameters during ischaemia and reperfusion between the groups. In the ANP group, the prevalence and frequency of ventricular extrasystoles within 10 min after reperfusion decreased markedly [ANP 22% vs. control 100%, P < 0.01, and ANP 1 (1) vs. control 92 (50), P < 0.05, respectively]. No dog in the ANP group had ventricular fibrillation (VF), but the incidence of VF was not statistically significant between the groups [ANP 0% vs. control 25%]. ATP content in the inner layers of the ischaemic myocardium in the ANP group was higher than in controls (P < 0.05) [1.92 (0.28) vs. 1.18 (0.13) mumol/g wet weight]. There was no significant difference in the content of myocardial tissue angiotensin II between the groups. CONCLUSIONS These data show that the infusion of ANP has cardioprotective effects on myocardial ischaemia and reperfusion in this model. These beneficial effects are probably due to direct effects through cGMP rather than haemodynamic changes.

Heart rate variability before the occurrence of silent myocardial ischemia during ambulatory monitoring

Thirty-three ischemic episodes in 19 patients with stable coronary artery disease were studied to clarify changing autonomic nervous system activity during daily life before the occurrence of myocardial ischemia. Nonischemic points were studied for comparison of control data with ischemic episodes. These were defined as (1) patient showing no ischemic ST-T change while having the same heart rate with onset of ischemic episodes, and (2) presence within 1 to 2 hours before or after onset of ischemic episodes in the same patient. We analyzed heart rate (HR) variability during the 30-minute period before the onset and after the end of ischemic episodes during 24-hour monitoring. The period of 30 to 40 minutes before ischemia was regarded as the baseline, and HR variability was analyzed at 10-minute intervals before each ischemic episode and nonischemic point. HR variability was quantified on the band of 2 components: low frequency (0.04 to 0.15 Hz; LF) and high frequency (0.15 to 0.40 Hz; HF). Of the 33 episodes, 24 (73%) had a greater LF/HF value during the 30-minute period before ischemia than that before the nonischemic points. Distribution of the number of the 24 episodes demonstrated circadian rhythm with a peak from 8 to 10 A.M. HF power began to decrease from the last 10 minutes before ischemia, compared with baseline. A significant decrease in HF power with a background of greater value of LF/HF may explain the reduced ischemic threshold for ischemia during daily life.

HEMATOPORPHYRIN DERIVATIVE UPTAKE BY ATHEROMA IN ATHEROSCLEROTIC RABBITS: THE SPECTRA OF FLUORESCENCE FROM HEMATOPORPHYRIN DERIVATIVE DEMONSTRATED BY AN EXCIMER DYE LASER

Abstract A new diagnostic and therapeutic endoscopic system consisting of an excimer pulse dye laser is presented. This report demonstrates the accumulation of hematoporphyrin derivative (HpD) in atheroma as shown by the fluorescence of HpD using this equipment. Atheroma was induced in the aorta of WHHL (Watanabe heritable hyperlipidemic) rabbits, 5 mg kg−1 HpD was injected intravenously and the rabbits were sacrificed 24 h later. The aorta was dissected and the localization of HpD was examined. Characteristic peaks of the fluorescence of HpD at 630, 665 and 690 nm wavelength were detected in the atheromatous lesion. However, in the fatty plaque, the emission peak at 630 nm was lower and the 665 nm peak faded away. No fluorescence with peaks was detected in the normal area. The ratio of fluorescence intensity in atheroma, border zones and normal areas was 10.4 : 5.0 : 1.0. On normal rabbits made atherosclerotic by diet and balloon damage, an ultra thin endoscopic catheter was inserted from the descending aorta of atherosclerotic rabbits under anesthesia. Essentially the same data was obtained by these studies in vivo as was obtained in the in vitro studies. The above data suggests the possibility of future applications of this equipment for diagnosis of atheroma.

In vivo intravascular laser photodynamic therapy in rabbit atherosclerotic lesions using a lateral direction fiber

This study was performed to evaluate the possibility of inducing regression of atherosclerotic foci by photodynamic therapy (PDT) using hematoporphyrin derivative (HpD).

Photodynamic therapy for the prevention of restenosis after angioplasty

The purpose of this study was to evaluate whether photodynamic therapy (PDT) can destroy the proliferating smooth muscle cells and therefore suppress the occurrence of restenosis after angioplasty. PDT following administration of hematoporphyrin derivatives (HpD) 24 hours before irradiation was performed on 30 rabbits immediately (0D), 3 days (3D), 1 week (1W) and 2 weeks (2W) after balloon injury. HpD accumulation of each group was investigated simultaneously. Irradiation of 27 J/10 mm2 from an Hg-Xe flash lamp light transmitted through an 800 micrometers quartz fiber with a diffusing tip was used. All rabbits were sacrificed 4 weeks after balloon injury. The results were expressed in terms of intima:media thickness ratio at the site of fiber contact (I/M) and intima:media area ratio of the cross section (IA/MA). Inhibition of intimal thickening evaluated on the basis of the I/M ratio was recognized in the 3D-, 1W-, and 2W-PDT group. The most effective photoradiation was at the 1W-PDT (I/M equals 0.78 +/- 0.67), but in 2W-PDT intimal necrosis resulting in a small amount of thickness was observed with less media necrosis. ThreeD and 0D PDT effects reduced with media necrosis. We conclude that PDT after angioplasty would be an ideal preventional therapy of restenosis.

Body surface mapping criteria for diagnosis of left ventricular hypertrophy associated with complete right bundle branch block

The standard electrocardiographic (ECG) criteria for left ventricular hypertrophy are unreliable in patients with complete right bundle branch block. This study was undertaken to formulate criteria for diagnosing these patients by using body surface mapping. The echocardiographic left ventricular mass was calculated by the Penn method from M-mode measurements. Of 56 patients, 27 were defined as having left ventricular hypertrophy with a left ventricular mass of 215 g or more. Isopotential and isointegral maps of the QRS complex were observed. The QRS isointegral maps were separated into two parts at the end of the downstroke of the initial R wave of vector spatial magnitude. The body surface mapping criteria with the highest sensitivity were EPmax (maximum of early part of the QRS) 45 microV.s or greater (sensitivity 93%, specificity 90%), EPmax/d (EPmax averaged by EP duration) 0.8 mV or greater (sensitivity 93%, specificity 97%), and Max (initial maximum) 2.2 mV or greater (sensitivity 89%, specificity 90%). These results suggest that body surface mapping is a useful technique in diagnosing patients with left ventricular hypertrophy and right bundle branch block.

Evaluation of multidirectional fluorescence-sensing laser catheter for the development of an intelligent laser angioplasty system

The differential diagnostic capacity of a multi-directional sensing catheter with intraluminal objects was evaluated by fluorescence analysis following administration of a photosensitizer. The measurement catheter is 1.7 mm in diameter and is constructed with a cross-sectional arrangement of 6 sensor bundle units and a centered guide wire lumen. Fluorescence was analyzed by polychrometer and amplified CCD camera with an image intensifier. The excitation light was 405 nm wavelength obtained from an Xe-Hg lamp using a band pass filter. In vivo and in vitro fluorescence analysis of normal and atherosclerotic rabbit aorta was performed following intravenous administration of 5 mg/kg hematoporphyrin derivatives (HpD) 24 hours before. The multi-directional sensing catheter detected fluorescence spectra independently in real time. In vivo measurement of this catheter showed, relative to the tip of catheter, in which direction there was blood, normal intima, slight intimal thickness, which should not be treated by laser, or areas of atherosclerosis, which can be treated by laser.

Detection of silent myocardial ischemia patients by the spatial velocity electrocardiogram.

This study was designed to detect patients with type I silent myocardial ischemia (SMI) at rest by assessing the symmetry of the electrocardiographic (ECG) T wave using the spatial velocity electrocardiogram (SVECG). In this study, the ECG T waves in patients with SMI were symmetric compared with those in normal subjects, and the the c/a ratio in the SVECG-T wave as the index of degree of symmetry of the ECG T wave enabled us to diagnose 73% of these patients; the c/a ratio in the SVECG T wave was a useful index for detecting patients with type I SMI at rest.