Tomohiko Shigemasa

ANGIOTENSIN II BLUNTS, WHILE AN ANGIOTENSIN-CONVERTING ENZYME INHIBITOR AUGMENTS, REFLEX SYMPATHETIC INHIBITION IN HUMANS*

1. The role of angiotensin (Ang)II in and the effects of angiotensin‐converting enzyme (ACE) inhibitors on the regulation of sympathetic neural activity were examined in humans.

Relation Between Body Fat–Corrected ECG Voltage and Ambulatory Blood Pressure in Patients With Essential Hypertension

Because adipose tissue has high electric resistance, the amount of body fat influences ECG voltage. In this study, body fat weight of patients with essential hypertension was measured by means of the impedance method and was used to correct mean ECG voltage. Then the relation between body fat-corrected mean ECG voltage (Vfm) and ambulatory blood pressure (BP) was investigated. The subjects were 172 patients with essential hypertension (88 men, 84 women, none receiving medication) between the ages of 30 and 75 years. Ambulatory BP was measured by a multi-biomedical recorder. Minimum sleep-time BP (base BP) was calculated to correspond with minimum sleep-time heart rate. The tetrapolar bioelectric impedance method was used to measure body fat (kg). Left ventricular mass (LVM) was obtained by echocardiography. Then comparisons were made with standard 12-lead ECG, and the statistical mean ECG voltage (Vm) and Vfm were derived by multivariate statistical analysis. The following formula was devised to obtain Vfm resulting from the multivariate analysis that demonstrated a high correlation with LVM (r=0.85): Vfm=0.175(Body Fat)1/3xVm+0.5 (mV). The coefficient of correlation (r) between Vfm and ambulatory BP was not smaller than that between LVM and ambulatory BP. Base systolic BP demonstrated a significantly higher r value (r=0.83) with Vfm/BSA1/2 (where BSA is body surface area) than mean daytime SBP (r=0.65). In many subjects with white-coat hypertension, Vfm/BSA1/2 was <1.33 mV/m (34 of 38 cases; sensitivity, 89%; specificity, 89%). These results indicate that Vfm is a better indicator of hypertensive left ventricular hypertrophy and that it may be useful in estimating minimum sleep-time systolic BP and in diagnosing white-coat hypertension in the outpatient clinic.

Guanabenz combination therapy inhibits sympathetic nerve activity and regresses left ventricular hypertrophy.

The cardiovascular and sympatholytic effects of combination therapy with guanabenz were examined in 26 patients (48 ± 13 years old [mean ± SD]) with stage 2 and 3 hypertension. Included in the study were patients under treatment with conventional antihypertensive drugs whose systolic and diastolic blood pressure was above 140 and 90 mmHg, respectively. Blood pressure, heart rate, and sympathetic parameters such as plasma concentration of norepinephrine and muscle sympathetic nerve activity at rest as well as during ambulatory conditions, 24-hour urinary excretion of norepinephrine, and low frequency (LF: 0.04–0.15 Hz)/high frequency (HF: 0.15–0.4 Hz) power ratio as a marker of cardiac sympathetic activity during 24 hours were examined before and after guanabenz (4–8 mg/d) combination therapy with first-line antihypertensive drugs such as diuretics. Left ventricular mass index (LVMI) was also calculated by conventional echocardiography. After 32 weeks of guanabenz combination therapy, systolic and diastolic blood pressure, heart rate, plasma and urinary excretion of norepinephrine, muscle sympathetic nerve activity, and LF/HF power ratio were significantly decreased, while neither LF nor HF power was changed. LVMI was also significantly decreased (270 ± 81 vs. 236 ± 83 g/m2, p < 0.005). These results indicate that guanabenz combination therapy inhibits sympathetic nerve activity under resting conditions as well as during ambulatory conditions and may accelerate regression of left ventricular hypertrophy in patients with moderate to severe hypertension.

Long-term follow-up in patients with intra-Hisian atrioventricular block

Long-term follow-up was performed in patients with intra-Hisian atrioventricular (AV) block who were implanted with permanent pacemakers. Subjects were 14 consecutive patients (3 men and 11 women, 65.4±9.7 [SD] years old), who exhibited intra-Hisian block at the time of pacemaker generators were replaced due to battery depletion. Electrophysiological examinations were performed at both the initial implantation and pacemaker replacement. The mean duration from the initial implantation to the replacement was 9.4±4.3 years. All patients had severe symptoms such as syncope, dizziness, or dyspnea, and these symptoms were relieved by pacemaker implantation. Seven patients had complete AV block, and the other seven had advanced or paroxysmal AV block at the time of implantation. Seven patients, who had advanced AV block at the time of implantation, developed complete AV block. Five of the seven patients who had complete AV block at the time of implantation remained in complete AV block, one patient had advanced AV block, and one patient of complete AV block increased significantly from 50% to 93% during the two electrophysiological examinations (P<0.05). A mean heart rate of 40.3±7.5 beats/min was observed during complete AV block. At the time of implantation, two patients were misdiagnosed as having AH block, and the other two patients were misdiagnosed as having HV block. In conclusion, intra-Hisian AV block gradually developed from advanced or paroxysmal AV block into complete AV block. Because the diagnosis of intra-Hisian block is sometimes difficult, we should always consider the possibility of intra-Hisian block in patients with severely symptomatic AV block.