Frequency domain heart rate variability and plasma norepinephrine level in the coronary sinus during handgrip exercise.

BACKGROUND: Heart rate (HR) variability has been recognized as an important noninvasive index of autonomic nervous activities. However, the relationship between HR variability and cardiac circulating norepinephrine (NE), especially with respect to coronary ischemia, remains unclear. HYPOTHESIS: This study was undertaken to determine whether HR variability indices can reflect cardiac NE levels during handgrip exercise. METHODS: We simultaneously measured HR variability and cardiac NE overflow rate in 32 patients (30 men, 2 women) during a 6-min isometric handgrip exercise. Among the 32 subjects, 20 (19 men, 1 woman) had coronary artery disease (CAD) and 12 (control group; 11 men, 1 woman) did not. RESULTS: Hemodynamics and cardiac NE overflow rates among subjects at rest were not significantly different between the two groups. In the normal subjects, low-frequency (LF) spectra and LF/HF (high-frequency) ratios were not significantly changed during handgrip exercise, but HF spectra significantly increased from 10.1 +/- 4.5 to 12.2 +/- 7.0 ms (p < 0.05). In the subjects with CAD, LF and LF/HF spectra were significantly (p < 0.05 and 0.01, respectively) increased by handgrip exercise. High-frequency spectra were not significantly changed by handgrip exercise. In the normal subjects, a significant negative relation (r = -0.76, p < 0.01) was obtained between HF change and cardiac NE overflow rate, whereas this relationship was not significant in the subjects with CAD. The correlation between changes of LF/HF and cardiac NE overflow rate was significant in the normal (r = 0.56, p < 0.05) but not in subjects with CAD. CONCLUSION: These results suggest that vagal modulation of HR variability is more prominent in normal coronary artery subjects than in CAD subjects during handgrip exercise. Heart rate variability indices may thus serve as adequate indicators of autonomic nerve activity in subjects with normal coronary arteries but not in those with CAD, probably due to decreased adaptation to physical stress during handgrip exercise.

Exercise-induced T-wave alternans as a marker of high risk in patients with hypertrophic cardiomyopathy.

Microvolt-level T-wave alternans (alternating morphology from beat to beat) during atrial pacing and exercise may predict ventricular tachycardia (VT) and fibrillation (VF) in ischemic heart disease. We tested whether such alternans during exercise could identify high-risk patients with hypertrophic cardiomyopathy (HCM). We studied 14 HCM patients and 9 normal control subjects for T-wave alternans u sing the CH2000 system with 7 multisegment electrodes in a Frank orthogonal (XYZ) configuration. Bicycle ergometer exercise was used to increase the heart rate (HR) to 95-110 beats/min. Seven patients were at high risk for ventricular arrhythmias (1 with sustained VT, 3 with abnormal paced ventricular electrograms as seen in VF survivors, and 3 with nonsustained VT and/or an adverse family history), and the other 7 were at low risk. T-wave alternans was present if alternans > 1.9 microV was consistently present with the HR in excess of a patient-specific HR threshold. Alternans was found in 5 of 7 high-risk patients (71%) vs none of 7 low-risk patients or 9 control subjects (p < 0.025 and p < 0.01, respectively). Notably, all 4 patients with sustained VT or abnormal ventricular electrograms showed alternans. Thus, high-risk patients with HCM often show T-wave alternans. Microvolt-level alternans during exercise may be a useful marker for ventricular arrhythmic risk in patients with HCM.

Autonomic modulation of ventricular rate in atrial fibrillation.

This study investigated the changes in R-R interval in 23 patients (11 men and 12 women; mean age 61 yr) with persistent atrial fibrillation in response to several provocative maneuvers including active postural change, Valsalva maneuver, handgrip, and rhythm-controlled respiration. Averaged R-R intervals were shortened immediately after postural change (from 797 +/- 35 ms supine to 677 +/- 27 ms standing; P < 0.01) and recovered to the 90% level within 100 s. During Valsalva strain and handgrip, mean R-R intervals were significantly shortened (from 737 +/- 37 ms sitting to 697 +/- 38 ms in Valsalva and from 773 +/- 68 ms sitting to 701 +/- 58 ms in handgrip; both P < 0.01). During rhythm-controlled respiration, only two cases (10.5%) showed power peaks in spectrograms of moving-window-averaged R-R intervals at the frequency corresponding to respiration rhythm. The ventricular response to atrial fibrillation is influenced by an increase in sympathetic tone and a decrease in parasympathetic tone but is not necessarily influenced by the increase in parasympathetic dominance. These results suggest that even in atrial fibrillation patients, the autonomic nervous system modulates the ventricular rate via the atrioventricular node and atrial tissue.

Angioscopic coronary macromorphology after thrombolysis in acute myocardial infarction.

In addition to a disruption of yellow plaque, vasospasm may also play a role in thrombotic occlusions of coronary arteries in small cases of infarction. Macroscopic vascular injury and thrombus seemed to be unnecessary for vasospasm culminating in myocardial infarction.

Efficacy of direct injection of ethanol into the myocardium to control aconitine-induced ventricular tachycardia in anesthetized dogs.

The effect of injecting ethanol directly into the myocardium to control aconitine-induced ventricular tachycardia (VT) was evaluated in anesthetized dogs. In 17 dogs, VT was induced by injecting aconitine (1.0 microgram, median dose) directly into the epicardium. After inducing persistent VT for up to 3 min, 0.6 ml (median volume) of 96% ethanol was injected into the same epicardial region. Regular sinus rhythm reappeared in 15 dogs with no change in systolic blood pressure; the other 2 dogs died of ventricular fibrillation (VF). In another 13 dogs, VT was induced by injecting aconitine directly into the endocardium using a Variocath needle catheter. After persistent VT for up to 3 min, a regular sinus rhythm was restored in 7 dogs by injecting 2.0 ml (median volume) of 96% ethanol; the remaining 6 dogs died of VF. Histology showed no transmural necrosis and the subendocardial necrotic areas were essentially the same in the dogs that recovered from VT as in those that died. There was no statistically significant relationship between doses of ethanol and VT duration. These preliminary results suggest that the injection of ethanol into the myocardium may efficiently terminate VT when other techniques fail.

Changes of QT intervals associated with postural change in patients with chronic atrial fibrillation.

Although different computerized systems have been developed to localize specific patterns in electrocardiographic (ECG) signals, it is still difficult to detect T waves and measure QT intervals during atrial fibrillation. This article demonstrates the use of an auto-correlation (ECG) based system that was used to investigate the dynamicity of QT intervals related to active postural change in patients with chronic atrial fibrillation. Twenty patients (9 male, mean age 63 years) with chronic atrial fibrillation (8 idiopathic, 12 organic heart disease) were examined. Seventeen of these patients were on digoxin, but patients with other conditions potentially affecting the autonomic nervous system were not included. A 3-channel ECG was recorded digitally during active postural change from supine to standing. Data were first analyzed by the Burdick Altair system and subsequently processed using an in-house software package evaluating auto-correlations of ECG signals. An ECG channel with suitable repolarization patterns was found in 15 patients. The mean QT interval of 409.8 +/- 11.1 ms (mean +/- SE) recorded during supine position shortened to 401.9 +/- 9.89 ms during the first minute of active standing (P < 0.05) and to 394.8 +/- 10.0 ms during the second minute of active standing (P < 0.005). It did not further change during the subsequent minutes of active standing. The study shows that automatic detection of QT intervals during atrial fibrillation is possible. Although the effect of position change of the heart cannot be completely excluded, the study suggests that QT interval is changed directly by autonomic nervous mechanisms rather than indirectly via the mean heart rate.

The effects of orally administered atenolol on the coronary hemodynamics and prostaglandin metabolism in angina pectoris patients.

The effects of oral atenolol on coronary hemodynamics and prostaglandin metabolism have been investigated in 8 chronic stable angina pectoris patients who underwent the supine bicycle ergometer. At rest, atenolol taken orally reduced the pressure-rate product significantly (P < 0.05) but did not significantly affect the coronary sinus blood flow or the coronary sinus pressure. During exercise, atenolol also reduced the pressure-rate product significantly (P < 0.05) but did not significantly affect the coronary sinus blood flow, the coronary sinus pressure, or the coronary vascular resistance. Atenolol also did not significantly affect the thromboxane B2/6-keto prostaglandin F1 alpha ratio in the arterial blood before and after exercise but did reduce this ratio in the coronary sinus blood by 15% from 1.9 +/- 1.1 to 1.5 +/- 0.46 (P < 0.10) after exercise. These results indicate that atenolol taken orally does not significantly depress the coronary hemodynamics. However, the effects of atenolol on the prostaglandin metabolism could not be clearly determined.

[Current status and problems of a screening for prostatic cancer in the health facilities in Fukuoka Prefecture].

We analyzed the current status and problems of a screening for prostatic cancer (PCa) through a health examination in 12 hospitals in Fukuoka prefecture. From 1987 to 1991, a total of 16,126 subjects received this. The number of subjects who received this increased every year. In 5 hospitals in which such a screening is optional, however, only about 20% of subjects through a health examination received it each year. Furthermore, most of the subjects were in their 50s or 40s. Those in their 70s or more who are at higher risk for PCa rarely received such screening. PCa was detected in 6 subjects (0.04%) (well differentiated adenocarcinoma: 3, moderate differentiated adenocarcinoma: 3) in 5 years. Five were in stage B and treated with radical prostatectomy and one was in stage C and hormonal therapy was performed. The mean age of the 6 patients was 57.7 year old ranging from 51 to 66. The incidence of PCa detected by a screening in dock increased with age. Prostate specific antigen (PSA) was considered to be more useful for detecting prostate cancer in dock as compared with digital examination (DRE), transrectal ultrasonography or prostatic acid phosphatase because of its relatively high sensitivity (83.3%) and specificity (84.8%). The incidence of PCa detected with combination of DRE and determination of PSA was 0.15% and significantly higher than that detected with DRE alone, 0.01%. These results suggest the need for enlightenment on PCa and the significance of a screening with combination of DRE and determination of PSA through a health examination for detecting early stage of PCa.

Usefulness of plasma beta-endorphin level, pain threshold and autonomic function in assessing silent myocardial ischemia in patients with and without diabetes mellitus.

The differences between diabetic and nondiabetic patients with silent myocardial ischemia were investigated. Based on the results of previous exercise testing, a total of 110 patients (15 diabetic and 95 nondiabetic) with exercise-induced myocardial ischemia were divided into the following 3 groups: 15 diabetics with silent myocardial ischemia, 49 nondiabetics with silent myocardial ischemia, and 46 nondiabetics with anginal symptoms. All patients underwent treadmill exercise testing and 24-hour ambulatory electrocardiographic recording. Before and during exercise, blood samples from the antecubital vein were obtained to determine the plasma beta-endorphin levels, and the pain threshold of each patient was measured with the electrical skin stimulation test. Furthermore, with regard to the ambulatory electrocardiographic recording, the mean of the SDs of all normal sinus RR intervals during successive 5-minute recording periods over 24 hours was analyzed and considered as an index of the autonomic function. The plasma beta-endorphin level during exercise was significantly greater in nondiabetic patients with silent ischemia than in diabetic ones. The SD mean was significantly less in the diabetic group than in the 2 nondiabetic ones. The findings suggest that the role of beta endorphin in diabetic patients with silent myocardial ischemia may be less significant than in nondiabetic ones; therefore, a diabetic neuropathy that affects the autonomic pain fibers that innervate the heart may be involved in the mechanism of silent myocardial ischemia in diabetics.

Effect of diltiazem on silent ischemic episodes, plasma bradykinin and prostaglandin metabolism.

Plasma bradykinin and prostaglandin metabolism are related to the anginal pain modulating system in patients with ischemic heart disease. We carried out a placebo controlled single blind test of diltiazem (30 mg three times a day) in 15 patients with chronic stable angina. The effect of diltiazem was evaluated by exercise treadmill testing and 48-h ambulatory electrocardiographic monitoring. Plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels were determined by radioimmunoassay prior to and during diltiazem therapy. Diltiazem significantly increased the exercise time and reduced episodes of angina. Diltiazem, however, did not appreciably improve either the frequency of silent myocardial ischemic episodes or the total duration of the silent myocardial ischemic episodes. Diltiazem also tended to decrease plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels. When ischemic episodes on ambulatory electrocardiographic monitoring are categorized according to heart rate change at the onset of episode (type A, preceded by heart rate increase > or = 5 beats/min; type B, no preceding heart rate increase), diltiazem was only effective on type A ischemic episodes as well as on symptomatic ischemia. Further, bradykinin was significantly decreased by diltiazem only in patients with exercise-induced silent ischemia or no exercise-induced ischemia, while the thromboxane B2/6-keto-prostaglandin F1 alpha ratio was unaffected by the administration of diltiazem. Thus, silent and symptomatic ischemia may be associated with different bradykinin and prostaglandin responses.

Heart rate variability in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure.

The prognosis of patients with heart disease and prediction of sudden cardiac death can be assessed through heart rate variability, an indirect measure of abnormal autonomic control. The authors have evaluated the heart rate variability by 24-hour ambulatory electrocardiographic monitoring in 25 diabetic patients, 19 ischemic heart disease patients, 18 congestive heart failure patients, and 10 normal subjects. Thirteen diabetic patients had autonomic neuropathy and 12 patients did not. Heart rate variability index (mean SD) in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure was significantly lower (34.5 +/- 12.6 ms, 43.7 +/- 15.4 ms, and 34.6 +/- 15.8 ms vs 65.6 +/- 16.7 ms, p less than 0.05) than that of normal subjects. Mean SD was significantly lower in patients with autonomic neuropathy as compared to patients without autonomic neuropathy (26.4 +/- 6.5 ms vs 44.2 +/- 11.0 ms, p less than 0.05) mean SD as compared to survivors: 49 +/- 7 ms in patients with mild ischemic heart disease, 48 +/- 15 ms in patients with severe ischemic heart disease, and 23 +/- 7 ms in patients who died. Similarly, the mean SD in 4 congestive heart failure patients who died was lower significantly (p less than 0.05) than in those who survived (19.0 +/- 5.6 ms vs 40.0 +/- 14.5 ms). Among congestive heart failure patients, clinical improvement by therapy was associated with a significant increase in mean SD. When the mean SD of 30 ms was used as the cutoff point for detection of autonomic dysfunction or patient death, specificity exceeded 90% and sensitivity was 75%.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma bradykinin and prostaglandin metabolism and exercise testing in patients with silent myocardial ischemia compared with patients with painful myocardial ischemia.

Bradykinin, alone or in combination with prostaglandin, is thought to produce pain in patients with coronary heart disease. To elucidate this further, we have investigated and compared serum bradykinin, TXB2 and 6 KPGF1 alpha levels in patients with silent myocardial ischemia (SMI, n = 18), painful myocardial ischemia (PMI, n = 8) and normal subjects (NL, n = 18). In addition, SMI and PMI subjects were given exercise testing and the results then compared. After Holter monitoring for 48 hours, exercise testing was performed. Blood was sampled in the morning between the Holter and exercise regimen. Maximal heart rate, systolic blood pressure and the double products were not significantly different between the SMI and PMI groups. The duration of exercise for the SMI group was 7.08 +/- 2.1 min vs 5.9 +/- 1.9 in the PMI group (p less than 0.10). Plasma bradykinin was 14 +/- 3 pg/ml in the SMI group and 15 +/- 3 in the PMI group (N.S), whereas it was 7 +/- 4 in the NL (p less than 0.05). The TXB2/6KPGF1 alpha for the SMI group was 1.3 +/- 0.3, which was significantly higher than that for the NL group (0.8 +/- 0.3, p less than 0.01), though this did not greatly differ from the PMI group (1.2 +/- 0.3). These results suggest that SMI patients under Holter monitoring who manifest no symptoms but show significant ST segment depressions must receive the same careful attention given to PMI patients. In both group of patients bradykinin and prostaglandin metabolism is similarly changed, as was demonstrated by exercise stress testing.