A transesophageal echocardiographic study on risk factors for stroke in elderly patients with atrial fibrillation: a comparison with younger patients.

STUDY OBJECTIVES: Atrial fibrillation (AF) becomes an increasingly important cause of stroke as patients get older. The aim of the study was to determine whether risk factors of cerebral embolism among elderly patients with AF differed from those of younger patients by using transesophageal echocardiography (TEE). DESIGN AND SETTING: Cross-sectional study at a university hospital. METHODS: Cardiovascular lesions with the potential for thromboembolism in patients with AF were investigated using TEE. Left atrial spontaneous echocardiographic contrast (SEC), peak flow velocity in the left atrial appendage (LAA-flow), and aortic atherosclerosis of the thoracic aorta were assessed in 67 elderly (> or = 70 years old) and 135 younger (< 70 years old) patients. All patients underwent either brain CT (n = 54) or MRI (n = 148) to assess presence of cerebral infarction. RESULTS: Cerebral infarction due to embolism was noted in 113 patients with AF. There was a higher prevalence of cerebral embolism in elderly patients when compared with younger patients (78% vs 45%; p < 0.001). Cerebral embolism found in younger patients was associated with high grade of SEC and lower LAA-flow (p < 0.05). In addition to these TEE findings, aortic atherosclerosis was more severe in elderly patients with cerebral embolism than in those without cerebral embolism (p < 0.0001). By multivariate logistic analysis, LAA-flow was an independent predictor of cortical infarction in younger patients, but not in elderly patients, whereas aortic atherosclerosis was a useful marker in predicting embolic risk in elderly patients. CONCLUSIONS: TEE findings indicative of left atrial blood stasis were useful to identify the embolic risk of younger patients with AF, while atherosclerosis of the thoracic aorta appears to be an important marker for cerebral embolism in elderly patients.

Respiratory modulation of muscle sympathetic nerve activity in patients with chronic heart failure.

BACKGROUND: Sympathoexcitation and respiratory instability are closely related to worsening of chronic heart failure. To elucidate the dynamic nature of respiratory modulation of sympathetic activity in patients with heart failure, we studied within-breath variation of muscle sympathetic nerve activity (MSNA) under various ventilatory volumes. METHODS AND RESULTS: MSNA, blood pressure, and respiratory flow were recorded in 23 patients with left ventricular ejection fraction

Relation of fibrillatory wave amplitude with hemostatic abnormality and left atrial appendage dysfunction in patients with chronic nonrheumatic atrial fibrillation.

Large left atrium (LA) and LA appendage (LAA) dysfunction are known to relate to cardiogenic thromboembolism, so the present study investigated the relation of the atrial fibrillatory wave (F wave) amplitude to hemostatic markers and LAA function. Transthoracic and transesophageal echocardiographic studies were performed in 82 consecutive patients with chronic, nonrheumatic atrial fibrillation (AF). Patients were divided into 2 groups according to F wave amplitude in lead V1 on the 12-lead ECG: coarse AF (the greatest amplitude of F wave > or =1 mm, n=44) and fine AF (<1 mm, n=38). Plasma levels of thrombin-antithrombin III complex, D-dimer, platelet factor 4 and beta-thromboglobulin were determined. Compared with patients with coarse AF, those with fine AF had lower LAA peak flow velocity (p<0.05) and higher prevalence of embolic cerebral infarction (50% vs 27%, p<0.05). Platelet activity did not differ between the 2 groups; however, plasma levels of thrombin-antithrombin III complex and D-dimer were significantly higher in patients with fine AF than in those with coarse AF (p<0.05). Multiple logistic regression analysis showed that fine AF was independently associated with cerebral embolism. Therefore, the presence of fine F wave in V1 would be a useful marker of LAA dysfunction and hypercoagulability, and indicate a risk for cerebral embolism in patients with chronic, nonrheumatic AF.

Instability of anticoagulation intensity contributes to occurrence of ischemic stroke in patients with non-rheumatic atrial fibrillation.

The efficacy of anticoagulation in reducing the risk of cardiogenic embolism has been demonstrated in patients with atrial fibrillation (AF), but there are few prospective studies assessing the influence of anticoagulation stability on ischemic stroke in such patients. Accordingly, the present study investigated prospectively whether an instability of the anticoagulation intensity would affect the efficacy of the therapy in a total of 156 patients with non-rheumatic AF (NRAF) who received oral anticoagulation with warfarin. During a 2-year follow-up period, the annual event rate of ischemic stroke was 2.1%. In patients without a history of prior stroke, no ischemic stroke occurred at a higher international normalized ratio (INR> or =2.0). In contrast, patients who had had a prior stroke had no INR-dependent reduction of incidence. The coefficient of variation (CV) of measured INRs was significantly greater in patients with ischemic stroke than in those without. By multivariate analysis, only greater CV (> or =0.3) of INRs was an independent risk for ischemic stroke, although New York Heart Association functional class > or =II and treatment with diuretics were of borderline significance by univariate analysis. The present results suggest that stability of anticoagulation intensity is important to protect thromboembolic events in patients with NRAF.

Modulation of ventricular repolarization and R-R interval is altered in patients with globally impaired cardiac 123I-MIBG uptake.

BACKGROUND: Cardiac (123)I-metaiodobenzylguanidine (MIBG) imaging is widely used to assess cardiac sympathetic neuronal function. However, physiologic significance of impaired cardiac MIBG uptake is not fully elucidated. The purpose of the present study was to determine influences of abnormal cardiac sympathetic neuronal function on heart rate variability (HRV) and ventricular repolarization process. METHODS: Twenty-nine patients with prior myocardial infarction were divided into two groups by a heart-to-mediastinum ratio (H/M) of MIBG scintigraphy. Ten patients with globally decreased MIBG uptake (group I: H/M < 1.5), 19 patients with partially decreased MIBG uptake (group II: H/M >or= 1.5), and 17 control subjects with normal MIBG uptake (group III) were studied. Holter recording and a standard 12-lead electrocardiography were used for evaluation of HRV, QT-RR relation, and QT dispersion. RESULTS: Low, high, and total frequency components decreased in groups I and II, as compared to that of group III. The reduction of these frequency domain measures was more severe in group I than in group II, but the differences did not reach statistical significance. Circadian variation of frequency domain measures disappeared in group I. The slope of QT-RR relation was significantly greater in group I than in groups II and III. QT dispersion was also greater in group I (64 +/- 25 msec) than in group II (43 +/- 19 msec) and group III (28 +/- 9 msec). CONCLUSION: These results suggest that patients with sympathetic neuronal dysfunction inferred from globally impaired cardiac MIBG uptake have an altered modulation of ventricular repolarization process as well as decreased HRV.

[Autonomic function and circulatory failure].

To define fundamental mechanisms for sympathoexcitation could provide a therapeutic opportunity to interrupt the specific site linking sympathetic activation with heart failure. Central sleep apnea is characterized by apnea, hypoxia, sleep fragmentation, and increased sympathetic nerve activity. Since this sympathoexcitation is directly related to the frequency of arousals from sleep and the degree of apnea-related hypoxia, but not to left ventricular ejection fraction, it is therefore not simply a compensatory response to hemodynamic derangement but is excessive and pathologic sympathoexcitation with aftereffects that persist into wakefulness. Thus, central sleep apnea could participate in a vicious pathophysiologic cycle involving the cardiovascular, respiratory, and autonomic nervous system.

Relation of transesophageal echocardiographic findings to subtypes of cerebral infarction in patients with atrial fibrillation.

BACKGROUND: Transesophageal echocardiography (TEE) has been used to identify the potential risk for cardiogenic embolism in patients with atrial fibrillation (AF). However, ischemic stroke in patients with AF is not always attributable to embolism. Identification of the risk of embolic versus atherothrombotic stroke should lead to the optimal individualized management of patients with AF. HYPOTHESIS: The goal of the study was to determine the relation between cortical infarction and perforating infarction and TEE findings in patients with AF. METHODS: We investigated the clinical usefulness of TEE in the risk stratification of clinical subtyping of the cerebral infarctions which were divided into two territories of the cortical branch (cortical infarction due to embolism) and deep perforators (perforating infarction due to atherothrombosis). Left atrial spontaneous echo contrast, peak flow velocity in the left atrial appendage, and generalized atherosclerosis as estimated by the intima-media wall thickness of the thoracic aorta were assessed by TEE in 118 consecutive patients with either paroxysmal (n = 44) or chronic (n = 74) AF. All patients underwent either brain computed tomography or magnetic resonance imaging. RESULTS: Cortical and perforating infarction was found in 39 and 18% of patients, respectively. The grade of spontaneous echo contrast was higher in patients with than in those without cortical infarction (p < 0.05). In contrast, patients with perforating infarction showed significant increase in the aortic wall thickness when compared with patients without perforating infarction (p < 0.05). In addition, multivariate logistic analysis revealed that spontaneous echo contrast was an independent predictor of cortical infarction, while intima-media wall thickness of the aorta, hypertension, and age were useful in predicting the risk of perforating infarction. CONCLUSIONS: Transesophageal echocardiography has a potential role in the risk stratification for cortical and perforating infarction in patients with AF.

[Abnormal Q wave in the right precordial leads unmasked during right bundle branch block in a patient with anteroseptal myocardial infarction: a case report].

Electrocardiography in a 77-year-old woman showed small R waves in leads V1-V3 3 hours after the onset of acute anteroseptal myocardial infarction. Abnormal Q waves appeared in leads V1-V3 only during intermittent right bundle branch block. The normal septal force disappeared after transmural septal infarction and a small force of right ventricle origin became apparent as a small R wave in V1. Right bundle branch block delayed activation of right ventricle, and thereby deleted the initial R wave and unmasked the Q wave of the septal infarction. Appearance of a Q wave in leads V1-V3 with right bundle branch block should not be assumed to reflect the extension of myocardial infarction.

Heterogeneous cardiac sympathetic innervation in heart failure after myocardial infarction of rats.

We examined cardiac neuronal function and beta-receptor with a dual-tracer method of [(131)I]meta-iodobenzylguanidine (MIBG) and [(125)I]iodocyanopindolol (ICYP) in rat heart failure after myocardial infarction (MI). In rats with MI, left ventricular (LV) systolic function decreased, and LV dimension and right ventricular (RV) mass increased gradually. MIBG accumulations of the noninfarcted LV (remote region) and RV decreased by 15% at 1 wk compared with sham-operated rats, and these accumulations were restored by 71% and 56%, respectively, at 24 wk compared with age-matched sham rats despite sustained depletion of myocardial norepinephrine contents in these regions. ICYP accumulation of the remote region and of the RV did not decrease at any stages. Myocardial MIBG distribution was heterogeneous at 1 wk when it was lower in the peri-infarcted region than in the remote region, associated with reduced ICYP accumulation in the peri-infarcted region. The heterogeneous distribution of both isotopes disappeared at 12 wk. Thus cardiac sympathetic neuronal alteration was coupled with downregulation of beta-receptors in rat heart failure after MI. The abnormal adrenergic signaling occurred heterogeneously in terms of ventricular distribution and time course after MI.

Time-varying spectral analysis of heart rate and left ventricular pressure variability during balloon coronary occlusion in humans: a sympathoexicitatory response to myocardial ischemia.

OBJECTIVES: We assessed time-varying spectral components of heart rate and left ventricular (LV) pressure variability during coronary angioplasty to elucidate dynamic autonomic responses to transient myocardial ischemia. BACKGROUND: Sympathoexcitatory reflexes elicited by acute coronary occlusion are rarely addressed in the clinical settings because of a lack of technique to monitor transient changes in sympathetic activation. METHODS: RR interval and LV pressure and volume were serially recorded in 14 patients with effort angina during balloon coronary angioplasty. Wavelet analysis was applied for determination of nonstationary spectral components of RR interval and LV peak pressure variability. RESULTS: The wavelet analysis revealed that coronary occlusion provoked low-frequency (LF) fluctuations of RR interval (seven patients) and LV peak pressure (six patients) at 0.06 +/- 0.01 Hz, but not in the remaining patients. Following the balloon inflation, the LF component of RR interval began to increase after the onset of myocardial ischemia, peaked at about 80 s, and then declined in the late phase of inflation. Consequently, the ratio of low to high frequency component rose to be significantly greater in the LF augmentation group than in the no LF augmentation group in the middle phase of coronary occlusion. The patients with no LF augmentation had little evidence of myocardial ischemia as reflected by changes in ST segment and LV systolic function during coronary occlusion. CONCLUSIONS: The wavelet analysis of RR interval and LV pressure variability clearly showed a dynamic profile of spectral components in response to transient coronary artery occlusion. The resultant regional myocardial ischemia elicited a profound sympathoexcitatory response followed by a gradual suppression. This method provides a useful tool to gain a new insight into the nonstationary autonomic influence on the cardiovascular system.

Modulation of left ventricular diastolic distensibility by collateral flow recruitment during balloon coronary occlusion.

OBJECTIVES: The goals of this study were to elucidate the scaffolding effect of blood-filled coronary vasculature and to determine the functional role of recruited collateral flow in modulating left ventricular (LV) distensibility during balloon coronary occlusion (BCO). BACKGROUND: Although LV distensibility is an important factor affecting acute dilation after myocardial infarction, the response of LV diastolic pressure-volume (P-V) relations to coronary occlusion is inconsistent in humans. METHODS: Micromanometer and conductance derived LV P-V loops were serially obtained from 16 patients undergoing percutaneous transluminal coronary angioplasty. Coronary collateral flow recruitment was angiographically evaluated by contralateral and ipsilateral contrast injection during BCO. RESULTS: In the group with poor collateral flow (grades 0-I; n = 8), BCO resulted in a downward and rightward shift of the diastolic P-V relations, where end-diastolic volume (EDV) increased by 13% (p < 0.05) without appreciable change in end-diastolic pressure (EDP; 18 +/- 6 to 18 +/- 8 mm Hg). In contrast, BCO in the group with good collateral flow (grades II-III; n = 8) shifted the diastolic P-V relations upward to the right with a concomitant increase in minimal pressure (min-P; 6 +/- 4 to 10 +/- 5 mm Hg, p < 0.05), EDP (15 +/- 7 to 21 +/- 9 mm Hg, p < 0.05) and EDV (+/- 10%, p < 0.05). Reactive hyperemia after balloon deflation caused a rapid and parallel upward shift of the diastolic P-V relations with a marked increase in min-P and EDP, especially in the group with poor collateral flow, before any improvement in LV contraction or relaxation abnormalities. CONCLUSIONS: Grades of coronary filling, either retrograde or anterograde, abruptly modulate LV distensibility through the rapid scaffolding effect of coronary vascular turgor.

[Inter-institute variations in International Normalized Ratio and thrombotest].

Oral anticoagulant therapy is effective for reducing the risk of thromboembolic events in patients with atrial fibrillation or other heart diseases. However, the intensity of oral anticoagulation therapy required in high risk patients, especially in Japanese patients, to achieve the best balance between the prevention of thromboembolic events and bleeding complications remains unclear. The multicenter study of Toyama Warfarin Rational Dosage (TOWARD) was started in 1996 to determine the optimal level of anticoagulant therapy. This study investigated the relationship between values of thrombotest (TT) and International Normalized Ratio (INR) measured from the same samples to clarify inter-institute variations. The relationship between TT and INR was not linear but hyperbolic. Changes of INR to TT are relatively small in the TT range of more than 20% as compared with the range of 20% or less. There were considerable inter-institute variations of TT, and the coefficient of variation (CV) was 0.16 and 0.24 in the low level and high level anticoagulation samples, respectively. However, the variations became significantly small when the same reference was used. The CV of INR was 0.12 and 0.08 in the high level and low level anticoagulation samples, respectively, and very similar with the control samples without anticoagulation (0.11). The variation was small when INR was obtained from the international sensitivity index (ISI) of thromboplastin less than 1.5. TT is widely used for monitoring oral anticoagulant therapy in Japan, and is an excellent system with little inter-institute variation when a standard reference is offered. Since INR has been established as an international monitoring system, the use of INR measured with thromboplastin of small ISI is recommended for monitoring.

Dual-tracer assessment of coupling between cardiac sympathetic neuronal function and downregulation of beta-receptors during development of hypertensive heart failure of rats.

BACKGROUND: Heart failure is associated with activation of the sympathetic nervous system and downregulation of beta-receptors. However, the coupling between cardiac sympathetic neuronal function and the beta-receptor during the development of hypertensive heart failure is not clear. METHODS AND RESULTS: We determined cardiac neuronal function and beta-receptors with a dual-tracer method of [131I]metaiodobenzylguanidine (MIBG) and 125I-cyanopindolol (ICYP) in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The rats were fed an 8% NaCl diet after the age of 6 weeks. Blood pressure was raised to >200 mm Hg at 12 weeks in DS rats and remained elevated until 18 weeks, but only slightly in DR rats. Left ventricular (LV) function of DS rats was preserved at 12 weeks but deteriorated at 18 weeks. Despite a 56% reduction of cardiac norepinephrine (NE) content at 12 weeks in DS rats, neither MIBG nor ICYP uptake in DS rats was different from that of DR rats. At 18 weeks, both MIBG and ICYP uptakes decreased, by 52% and 39%, respectively, in association with 71% reduction of cardiac NE, in DS rats. MIBG uptake of the LV was homogeneous at 6 weeks but was lower in the LV endocardial regions at 18 weeks in DS rats. CONCLUSIONS: The present results indicate that cardiac sympathetic neuronal function is relatively preserved at the compensated, hypertrophic stage of DS rats but deteriorates in association with beta-receptor downregulation at the failing stage. The cardiac neuronal dysfunction occurs heterogeneously. A combination of scintigraphic portrayal of beta-receptors with MIBG should provide valuable information regarding sympathetic nerve signaling in living hearts.

Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure.

To elucidate the time course of sympathovagal balance and its relationship to left ventricular function in heart failure, we serially evaluated left ventricular contractility and relaxation and autonomic tone in 11 conscious dogs with tachycardia-induced heart failure. We determined a dynamic map of sympathetic and parasympathetic modulation by power spectral analysis of heart rate variability. The left ventricular peak +dP/dt substantially fell from 3,364 +/- 338 to 1,959 +/- 318 mmHg/s (P < 0.05) on the third day and declined gradually to 1,783 +/- 312 mmHg/s at 2 wk of rapid ventricular pacing. In contrast, the time constant of left ventricular pressure decay and end-diastolic pressure increased gradually from 25 +/- 4 to 47 +/- 5 ms (P < 0.05) and from 10 +/- 2 to 21 +/- 3 mmHg (P < 0.05), respectively, at 2 wk of pacing. The high-frequency component (0.15-1.0 Hz), a marker of parasympathetic modulation, decreased from 1,928 +/- 1,914 to 62 +/- 68 x 10(3) ms2 (P < 0.05) on the third day and further to 9 +/- 12 x 10(3) ms2 (P < 0.05) at 2 wk. Similar to the time course of left ventricular diastolic dysfunction, plasma norepinephrine levels and the ratio of low (0.05- to 0.15-Hz)- to high-frequency component increased progressively from 135 +/- 50 to 532 +/- 186 pg/ml (P < 0.05) and from 0.06 +/- 0.06 to 1.12 +/- 1.01 (P < 0.05), respectively, at 2 wk of pacing. These cardiac and autonomic dysfunctions recovered gradually toward the normal values at 2 wk after cessation of pacing. Thus a parallel decline in left ventricular contractility with parasympathetic influence and a parallel progression in left ventricular diastolic dysfunction with sympathoexcitation suggest a close relationship between cardiac dysfunction and autonomic dysregulation during development of heart failure.

Effect of assisted circulation on left ventricular performance in a canine model.

BACKGROUND: Little is known about left ventricular performance during venoarterial bypass and left heart bypass (LHB) after cross-clamping the descending thoracic aorta. We evaluated the effects of venoarterial bypass and LHB on ventricular load optimization and left ventricular work efficiency. METHODS: We used the left ventricular conductance catheter and a micromanometer in 7 anesthetized mongrel dogs. We assessed preload by the end-diastolic volume, afterload by the effective arterial elastance, and left ventricular contractile properties by the slope of the end-systolic pressure-volume relationship. In addition, optimal ventricular arterial coupling (ratio of effective arterial elastance to slope of end-systolic pressure-volume relationship) and left ventricular work efficiency (ratio of external work to pressure-volume area) were calculated. RESULTS: The decrease in preload was much greater with LHB than venoarterial bypass. There were no significant differences in afterload and left ventricular contractility between venoarterial bypass and LHB. The ventricular arterial coupling during LHB was near 0.50 (0.69 +/- 0.16) in the "best heart" condition (effective arterial elastance = slope of end-systolic pressure-volume relationship/2), whereas the work efficiency during LHB was at maximum (0.73 +/- 0.12). CONCLUSIONS: We conclude that LHB has a more beneficial effect on left ventricular performance after cross-clamping of the descending thoracic aorta.

Quantitative evaluation of blood flow distribution to exercising and resting skeletal muscles in patients with cardiac dysfunction using whole-body thallium-201 scintigraphy.

BACKGROUND AND HYPOTHESIS: Decreased blood flow to working muscles makes an important contribution to exercise intolerance in patients with chronic heart failure. This study was undertaken to examine whether maldistribution of skeletal muscle blood flow is closely related to exercise intolerance in patients with cardiac dysfunction. METHODS: Whole-body thallium scintigraphy was performed during one-leg exercise in 11 patients with left ventricular (LV) dysfunction (LV ejection fraction < 45%). Blood flow distribution to the exercising and resting legs was quantified by expressing regional thallium counts as a percentage of the whole-body counts at rest, at the level of anaerobic threshold, and at peak exercise. RESULTS: At anaerobic threshold, the thallium activity of exercising muscle increased from 4.2 +/- 0.7 to 14.0 +/- 2.5% (p < 0.05) in the thigh and from 1.7 +/- 0.3 to 4.1 +/- 0.9% (p < 0.05) in the calf, compared with the resting value. Consequently, the ratio of thallium activity between exercising and resting legs increased to 2.7 +/- 0.7 (p < 0.05) in the thigh and to 2.3 +/- 0.7 (p < 0.05) in the calf. When plotted as a function of anaerobic threshold, thallium activity of the exercising thigh (r = 0.78, p < 0.05) and the thallium ratio between exercising and resting thigh (r = 0.69, p < 0.05) declined with the reduction of exercise tolerance. These correlations were not observed in calves. CONCLUSION: Whole-body thallium scintigraphy demonstrated a maldistribution of leg blood flow in patients with reduced aerobic exercise capacity, suggesting that this abnormality could play an important role in exercising intolerance in these patients.

[Transesophageal echocardiographic findings of cortical and perforating infarctions in patients with atrial fibrillation].

The predictive value of transesophageal echocardiography was investigated for the risk stratification of atherothrombotic or embolic cerebral infarction in patients with atrial fibrillation. Left atrial spontaneous echo contrast, peak flow velocity in the left atrial appendage and generalized atherosclerosis as estimated by the intima-media wall thickness of the thoracic aorta were assessed by transesophageal echocardiography in consecutive patients with paroxysmal (n = 25) or chronic (n = 60) atrial fibrillation (mean [+/-SD] age; 63 +/- 11 years). All patients underwent brain computed tomography or magnetic resonance imaging to evaluate the presence or absence of cerebral infarction. The location of cerebral infarction was divided into two territories, the cortical branch (cortical infarction) and deep perforators (perforating infarction), to evaluate embolic and atherothrombotic cerebral infarction, respectively. Cortical and perforating infarctions were found in 42% and 16% of all patients, respectively. The grade of spontaneous echo contrast was higher in patients with cortical infarction than in those without cortical infarction. Patients with perforating infarction showed thicker aortic wall compared with patients without perforating infarction. Other parameters had no predictive value to differentiate perforating from cortical infarctions. Multiple regression analysis revealed that spontaneous echo contrast and age were independent predictors of embolic cortical infarction, whereas intima-media wall thickness of the aorta and hypertension were useful in predicting the risk of atherothrombotic perforating infarction. Transesophageal echocardiography is useful for predicting embolic cortical infarction and atherothrombotic perforating infarction.

Vesnarinone-induced granulocytopenia: incidence in Japan and recommendations for safety.

Vesnarinone (OPC-8212) is a new positive inotropic agent that augments myocardial contractility. A recent multi-center randomized trial in the United States demonstrated that 60 mg/day of vesnarinone significantly reduced morbidity and mortality and improved quality of life in patients with symptomatic chronic heart failure. Vesnarinone, however, is also known for its propensity to cause granulocytopenia. In search of effective safety measures against this side effect, data have been collected in Japan as part of the post-marketing surveillance of this drug. This article reviews the results of this post-marketing surveillance and other works available to date, including an illustrative case report, and presents measures that should be taken with regard to safety during treatment with vesnarinone. Vesnarinone-induced granulocytopenia has appeared in relatively early stages of vesnarinone therapy, and characteristically results in a rapid decrease in granulocyte count. Hematologic monitoring should be performed at least once a week during the initial 16 weeks of vesnarinone therapy. Granulocyte colony-stimulating factor may contribute to recovery from severe granulocytopenia, although it should be used carefully because of its potential to cause adult respiratory distress syndrome.

Effects of water ingestion on gastric electrical activity and heart-rate variability in healthy human subjects.

Electrogastrography (EGG) is a method to record electrical activity of the stomach using cutaneous electrodes. Power ratio (PR) is one of the parameters and means the relative change of EGG power of gastric activity from before to after certain stimulations (e.g., meals, water or drugs). Autonomic nervous function is an important modulator of gastric activity, but its relation with the EGG parameters has not been well clarified. We recorded EGG and the R-R interval simultaneously both before and after drinking 150 ml water for 400 s, and spectrally analyzed them using the maximum entropy method in 12 healthy volunteers. We calculated PR from before to after water ingestion, and the power of the high-frequency component of R-R interval variability before (pre-HF) and after water ingestion (post-HF), and their ratio (rHF = post-HF/pre-HF). PR was positively correlated with rHR (r = 0.727; P < 0.05) and negatively correlated with pre-HF (r = 0.706; P < 0.05), and rHF was negatively correlated with pre-HF (r = 0.776; P < 0.05). These results suggest that simultaneous recording of EGG and ECG for frequency domain analysis is necessary to estimate the vagal nervous activity.