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Biomedical subjects

H Hayakawa

Publications and source records attributed to H Hayakawa.

At least 91 records · Page 5Linked to original sources

Wavelet transform system makes one-beat analysis possible in late potential evaluation.

High-frequency components of the QRS complex, including late potentials, can be analyzed by signal averaging (SA). However, this method may fail to detect transient changes as a result of cancellation. The wavelet transform, which has a superior time-frequency resolution, was used to analyze beat-to-beat changes of the QRS components in 50 normal subjects and 50 patients who showed positive late potentials. The transformed data, displayed in three dimensions and in color, were highly reproducible in each patient. Measurement of high-power duration at a frequency of 50 Hz (WD50) showed a significant correlation between WD50 and filtered QRS duration in both groups. When the mean +/- SD of WD50 in normal subjects was defined as normal, 96% of patients with late potentials were out of the normal range. The wavelet signals in patients with late potentials were more inhomogeneous than those of normal subjects. It is concluded that this newly developed color display, three-dimensional wavelet transform system showed extremely good time-frequency resolution in analyzing every beat without signal averaging.

Action Potentials↗

Effects of carbon monoxide exposure on serotonergic neuronal systems in rat brain.

It is well known that some psychiatric sequelae exist after CO poisoning, but few animal studies on serotonergic neuronal function after CO exposure have been carried out. We investigated the effects of successive carbon monoxide (CO) exposure (6000 ppm, 10 min, 3 repetitions) on serotonergic neuronal systems in rat brain. Serotonin (5-HT) concentrations were significantly decreased only in the frontal cortex from 1 hr to 7 days after CO exposure. 5-Hydroxyindoleacetic acid (5-HIAA) concentrations were significantly increased at 1 hr in all six brain regions measured (frontal cortex, striatum, hypothalamus, hippocampus, midbrain, and pons). 5-HT synthesis, measured by the accumulation of 5-hydroxytryptophan (5-HTP) after the administration of m-hydroxybenzylhydrazine (NSD-1015), was significantly decreased in all regions from 1 hr to 7 days after CO exposure. [3H]Ketanserin (5-HT2A) binding sites in the frontal cortex were not affected by CO exposure. DOI-induced head shakes, a 5-HT2A receptor mediated behavior, were not changed after CO exposure. These findings indicated that CO exposure caused presynaptic serotonergic neuronal dysfunctions that consisted mainly of decreased concentration of 5-HT in the frontal cortex or a decrease of 5-HT synthesis in all six regions, without compensatory hyperfunction of 5-HT2A receptors.

Amphetamines↗

Kinetics of buccal absorption of propafenone single oral loading dose in healthy humans.

Buccal absorption has an advantage when compared with other administration routes because of its rapid onset of action. We examined the pharmacokinetics of buccal-absorbed propafenone in healthy humans. 1. After a single oral administration of 150 mg of propafenone, the average peak concentration of propafenone was 27.9+/-2.5 ng/ml, and that of 5-hydroxypropafenone was 61.7+/-6.6 ng/ml (n=5). The times to reach peak serum concentrations of propafenone and 5-hydroxypropafenone were 1.8+/-0.1 hr and 1.5+/-0.2 hr, respectively. 2. After a buccal absorption of 150 mg of propafenone, the time to reach peak serum concentration of propafenone was 16.9+/-2.3 min (n=8). The average peak concentration of propafenone was 30.4+/-1.4 ng/ml (n=8), and the concentrations of 5-hydroxypropafenone were below the detection limit in all subjects. The rapid upstroke of serum concentrations of propafenone by buccal administration may cause rapid onset of pharmacological conversion.

Absorption↗

Electrophysiologic and hemodynamic effects of a single oral dose of pilsicainide hydrochloride, a new class 1c antiarrhythmic agent.

To establish the clinical efficacy of pilsicainide, we evaluated its electrophysiologic and hemodynamic effects after a single oral administration to 18 patients with documented supraventricular tachycardia (SVT). To determine the minimal effective blood level, changes in efficacy with time were evaluated by serial reinduction studies with venous blood sampling for measurement of the plasma pilsicainide level. Sixty minutes after administration of a single oral dose of pilsicainide, the sinoatrial conduction time, AH and HV intervals, and the effective refractory period of the right ventricle were prolonged. Ventriculoatrial conduction was blocked in 11 patients [nine of 12 via accessory pathway and two of six via the atrioventricular (AV) node], resulting in the suppression of SVT induction in nine of 13 patients. Pilsicainide increased the heart rate and mean pulmonary arterial pressure and decreased the stroke volume index at 60 min. PQ interval, QRS width, and QTc were significantly prolonged after pilsicainide, and the percentage prolongations of the PQ interval were well correlated with the plasma pilsicainide levels. The plasma level effective for suppression of SVT was considered to be >0.5 microg/ml. We concluded that a single oral administration of pilsicainide is well tolerated and effective in suppressing SVT.

Administration, Oral↗

Chronotropic effects of cilostazol, a new antithrombotic agent, in patients with bradyarrhythmias.

Whether phosphodiesterase inhibitors increase the heart rate in patients with bradyarrhythmias is not known. We attempted to determine whether the oral phosphodiesterase inhibitor cilostazol exhibits beneficial chronotropic effects in patients with symptomatic bradyarrhythmias. Twenty patients comprising eight with bradycardic atrial fibrillation, eight with sick sinus syndrome, and four with Wenckebach-type atrioventricular block, whose 24-h total heart-beat count was < or =70,000 beats and whose maximal RR interval was > or =2.5 s, were enrolled. Holter recordings (24-h) were made before and 2 weeks after oral daily administration of 200 mg of cilostazol. Cilostazol increased the 24-h total heart-beat count from 77,429 +/- 11,168 to 107,981 +/- 13,536 (95% confidence interval, 24,605-36,497; p < 0.0001), the minimal heart rate from 33 +/- 9 47 +/- 13 beats/min (95% confidence interval, 9-19 beats/min; p < 0.0001), and the maximal RR interval from 3,149 +/- 1,018 to 2,087 +/- 601 ms (95% confidence interval, -1,517 to -608 ms; p = 0.0001). Only two patients had headaches as adverse effects. In conclusion, cilostazol had a beneficial positive chronotropic effect in patients with bradyarrhythmias, especially with bradycardic atrial fibrillation and sick sinus syndrome.

Administration, Oral↗

Successful pregnancy after coronary artery bypass grafting for Kawasaki disease.

A 13-year-old girl with a history of Kawasaki disease underwent coronary artery bypass grafting because of angina pectoris due to a giant coronary artery aneurysm on the left main trunk artery. Nine years after the operation, the patient had an uneventful pregnancy followed by a normal vaginal delivery. This is the first case of a successful pregnancy after coronary artery bypass grafting for Kawasaki coronary artery disease.

Adolescent↗

Ventriculoatrial block during atrioventricular nodal reentrant tachycardia utilizing multiple retrograde pathways.

A rare case of narrow QRS tachycardia continuing despite the occurrence of VA block is reported. Right ventricular stimulation suggested dual AV nodal physiology. The tachycardia was induced by ventricular premature stimulation, which failed to depolarize the atrium. Two types of tachycardia that had different retrograde conduction sequences, HA intervals, and cycle lengths were induced. The occurrence of VA block did not terminate the tachycardia but transiently prolonged the tachycardia cycle length. These findings suggest the mechanism is AV nodal reentry utilizing multiple retrograde pathways with intranodal reentry bridging the VA block and maintaining the tachycardia.

Bundle of His↗

Mutual information discloses relationship between hemodynamic variables in artificial heart-implanted dogs.

A mutual information (MI) method for assessment of the relationship between hemodynamic variables was proposed and applied to the analysis of heart rate (HR), arterial blood pressure (BP), and renal sympathetic nerve activity (RSNA) in artificial heart-implanted dogs to quantify correlation between these parameters. MI measures the nonlinear as well as linear dependence of two variables. Simulation studies revealed that this MI technique furnishes mathematical features well suited to the investigation of nonlinear dynamics such as the cardiovascular system and can quantify a relationship between two parameters. To constitute a model free of the natural heart, two pneumatically actuated ventricular assist devices were implanted as biventricular bypasses in acute canine experiments. RSNA was detected with the use of bipolar electrodes attached to the renal sympathetic nerve. Analysis of data during control revealed that correlation between HR and RSNA was higher than that between HR and BP and that between RSNA and BP (P < 0.05). Although RSNA seemed to fluctuate noncorrelatedly with BP in higher pacing rates, the MI values between them disclosed their strong correlation. Surprisingly, correlation between RSNA and BP was stronger during a pacing rate of 60 beats/min than during higher pacing rates and control (P < 0. 05). It is suggested that the baroreflex system may be susceptible to pacing rates during the total artificial heart state. We calculated the time delay between HR and RSNA, between RSNA and BP, and between HR and BP by regarding a time delay at which the maximum MI value between each pair of parameters was given as a physiological delay. Our results indicate that RSNA leads BP, BP leads HR, and RSNA leads HR during control (P < 0.05). We conclude that this method could provide a powerful means for measuring correlation of physiological variables.

Algorithms↗

Glomerular injuries--excretion of glomerular epithelial cells-- induced by chemotherapy (antineoplastic drugs) independent of tubular damage.

For the purpose of studying glomerular injuries induced by antineoplastic drugs, the excretion of glomerular epithelial cells (GEC) was evaluated. In 13 children who received antineoplastic drugs, the excretion of GEC in urine samples was examined with an immunofluorescent study using a monoclonal antibody directed against podocalyxin, which was expressed on glomerular epithelial cells. GEC were detected in 20 of 25 chemotherapy courses. The excretion of GEC persisted until the next chemotherapy course in some cases. After an initiation of chemotherapy an increased urinary albumin-creatinine ratio (more than 2-fold) was found in 6 patients. A significant increase of N-acetylglucosaminidase was observed in 2 patients. Proteinuria and hematuria were not observed in all patients. These results indicate that glomerular injuries are frequently induced by chemotherapy independent of the tubular damage. Repeated glomerular injuries may result in late renal dysfunction.

Acetylglucosaminidase↗

Nitric oxide synthase activity and renal injury in genetic hypertension.

Nitric oxide (NO) is an endogenous vasodilator synthesized in the endothelium by constitutive NO synthase (cNOS). We have shown that upregulation of cNOS activity in hypertension may contribute to forestalling left ventricular and aortic hypertrophy (Hypertension. 29: 235, 1997). NO has been shown to inhibit growth-related responses affecting vascular smooth muscle, and mesangial cells, as well as reduce production of extracellular matrix in response to injury. Here, we investigated the relationship between renal cNOS activity (conversion of [14C] L-arginine to [14C] L-citrulline) and glomerular (GIS) and tubulointerstitial (TIS) injury scores and urinary protein excretion, indices of renal injury, in age and blood pressure matched spontaneously hypertensive rats (SHR, SBP 220+/-9 mm Hg) fed 0.5% NaCl diet and Dahl salt-sensitive (DS) rats fed 4% NaCl diet (DS-4%, SBP 228+/-8 mm Hg) as well as their normotensive counterparts Wistar Kyoto rats fed 0.5% NaCl diet (WKY, 137+/-3 mm Hg) and DS rats fed 0.5% NaCl diet (DS-0.5%, SBP 135+/-4 mm Hg). In SHR, renal medullary cNOS activity was 89% higher than in WKY (8.91+/-0.98 vs 4.71+/-0.37 nmol/min/g protein, P<0.05) whereas, in hypertensive DS-4% rats cNOS activity was 43% lower than in DS-0.5% rats (1.98+/-0.16 vs 3.48+/-0.29 nmol/min/g protein, P<0.05). Renal cortical cNOS was lower than in medulla but similar in all groups; inducible NOS activity was not detected. Despite hypertension of similar severity and duration, hypertensive DS-4% developed 9 fold more GIS (190+/-42 vs 21+/-11), 20 fold more TIS (4.0+/-0.7 vs 0.2+/-0.3), and 5 fold more proteinuria (54+/-11 vs 8.5+/-3.0 mg/day), all P<0.05. The current studies, in conjunction with our recent studies in heart and aorta, strongly suggest that in hypertension, increased cNOS activity may provide a protective homeostatic role in all the end-organs that are targets of hypertensive injury.

Animals↗

Histamine-releasing properties of T-3762, a novel fluoroquinolone antimicrobial agent in intravenous use. I. Effects of doses and infusion rate on blood pressure, heart rate and plasma histamine concentration.

T-3762, a newly developed fluoroquinolone antimicrobial agent, ciprofloxacin (CPFX) and ofloxacin (OFLX) were administered intravenously to anesthetized dogs by intravenous infusion, and blood pressure, heart rate and plasma histamine concentrations were monitored. T-3762 decreased blood pressure by 12.0%, without alterations in heart rate and plasma histamine concentration, only when infused at 150 mg/min. CPFX and OFLX both produced a rapid decrease in blood pressure in a dose-related manner, with an accompanying decrease in heart rate, but to a lesser extent. After infusion at 150 mg/min, CPFX caused death in 2 animals within a few minutes, while OFLX produced maximum decreases in blood pressure and heart rate, by 69.0% and 26.4%, respectively. The infusion of these 2 agents resulted in dose-related increases in plasma histamine concentrations parallel to the decreases in blood pressure: the maximum, attained with CPFX at 50 mg/min and OFLX at 150 mg/min, were 379.2 and 167.8 ng/ml, respectively. For CPFX and OFLX, the relationship between the maximum levels of decreased blood pressure and increased histamine concentration in plasma was highly significant. The hypotension induced by CPFX was efficiently reduced by the pretreatment of animals with antihistamines. The results from this study suggest that hypotension induced in dogs following the intravenous infusion of fluoroquinolone antimicrobial agents may be dependent on their ability to cause histamine release from cells and tissues, and indicates that T-3762 is devoid of this ability in comparison to CPFX and OFLX.

Animals↗

Purulent pericarditis with tamponade caused by Salmonella enteritidis.

The incidence of purulent pericarditis has declined. However, mortality remains high. We describe a case of purulent pericarditis with tamponade caused by Salmonella enteritidis, and emphasize the importance of early recognition, prompt institution of appropriate antibiotic therapy, and early surgical drainage for survival.

Adult↗

Coronary hyperreactivity to adrenergic stimulation and increased nocturnal vagal tone trigger coronary vasospasm.

The relationship between autonomic nervous system activity (ANA) and coronary vasoreactivity during transient myocardial ischemia was determined in patients with vasospastic angina (VA). ANA was measured by power spectral analysis of heart rate variability and humoral factors following intravenous infusion of insulin in 24 patients with VA and 6 control patients. Nine (38%) of the VA patients had significant ST segment depression (STD), and 4 of these patients had symptomatic STD. The frequency of anginal episodes in the 9 patients with VA and STD was significantly greater than that in the 15 VA patients without STD (3.4 +/- 3.1 vs 0.5 +/- 0.8 episodes/week, p < 0.05). The increase in the LF/HF ratio 30 min after insulin injection in patients with STD was significantly greater than that in patients without STD (34 +/- 31% vs 4 +/- 34%, p < 0.05). All of the patients with VA and STD had significant coronary vasospasm in response to the infusion of < or = 20 micrograms of acetylcholine, higher levels of nocturnal parasympathetic activity, and greater norepinephrine production in response to insulin stimulation than the VA patients without STD. These findings suggest that increased vagal tone and hyperreactivity to adrenergic stimulation may trigger vasospasm in patients with VA.

Aged↗

Detection of a local slow potential preceding the surface QRS complex during non-preexcited impulse propagation--a phenomenon reflecting anterograde concealed conduction through the accessory pathway?

A case of Wolff-Parkinson-White (WPW) syndrome with several interesting electrophysiologic findings is presented. Although manifest preexcitation had not been documented in clinical routine check-ups for the 2 years before the ablation session, an intermittent preexcitation emerged after an initial unsuccessful radiofrequency current delivery directed at the subvalvular mitral annulus 1 cm distal from the subsequent successful ablation site. During intermittent manifestation of preexcitation, the following observations were made: (1) during manifest preexcitation, a possible Kent potential was recorded at the successful ablation site; (2) during non-preexcited impulse propagation, a local slow potential preceding the QRS complex (pre-QRS potential) was clearly observed at the same site; (3) the pre-QRS potential disappeared during orthodromic atrioventricular reciprocating tachycardia, spontaneous atrial premature contraction and after the subsequent successful ablation; and (4) when the pre-QRS potential was obvious, a small change in QRS morphology of the body-surface ECG was appreciable, compared with that during beats of negative pre-QRS potential. A comparable preceding component was also detected in a signal-averaged ECG. It is considered that the pre-QRS potential might be related to the anterograde concealed conduction through the accessory pathway.

Electrophysiology↗

[Effect of phenylephrine, endothelin and angiotensin II on reperfusion arrhythmias. A role for Na+/H+ exchanger activation via protein kinase C].

Stimulation of receptors for alpha 1-adrenergic agonist, endothelin (ET) and angiotensin II (AT) activates the cardiac sarcolemmal Na+/H+ exchanger (NHE), perhaps via protein kinase C(PKC)-mediated pathway(s). We tested for the ability of these extracellular stimuli to exacerbate reperfusion arrhythmias and for the possible role of NHE activation and PKC in such phenomena. Isolated rat hearts (n = 12/group) were subjected to dual coronary perfusion. After 15 min of aerobic perfusion, flow to the left coronary bed was reduced to 5% of basal values for 12 min, and the same bed was then reperfused for 5 min. An alpha 1-adrenergic agonist phenylephrine (PE) at 1 or 10 mumol/L, ET at 0.5 or 5nmol/L or AT at 1 or 10mumol/L was infused selectively into the left coronary bed during 12 min of regional low flow ischemia. The incidence of reperfusion-induced ventricular fibrillation (VF) was increased from 17% in control to 33% and 75%* with 1 and 10 mumol/L PE(*p < 0.05 vs control) from 8% in control to 8% and 12% with 0.5 and 5 nmol/L of ET. However, AT had no effect. The selective NHE inhibitor NOE642 at 1 mumol/L, infused concomitantly with 10 mumol/L PE, reversed the proarrhythmic effects of PE; VF incidence was reduced from 67% to 8%*. However, glibenclamide (a blocker for the ATP-sensitive K+ channel) at 1 mumol/L did not affect the proarrhythmic effects of PE. Infusion of a specific PKC inhibitor GF109203X(GF) at 30 or 300 nmol/L, starting from 5 min before ischemia and maintained throughout ischemia concomitantly with 10 mumol/L of PE, was partially effective in reducing VF incidence; which reduced from 75% in control to 42% with 300 nmol/L of GF. These results suggest that, in rat hearts subjected to regional low-flow ischemia and reperfusion, stimulation of alpha 1-adrenergic receptor can exacerbate reperfusion-induced VF, whose mechanism(s) may involve NHE activation. Moreover, PKC activation does not appear to be the sole signaling mechanism for this phenomenon.

Adrenergic alpha-Agonists↗

Usefulness of exercise thallium-201 imaging in evaluation of low- and high-risk groups in coronary artery disease patients with disappearance of anginal episodes by anti-anginal drug therapy.

Our objective was to clarify the management of patients with silent myocardial ischemia (SMI) and documented coronary artery disease. We evaluated 222 such patients who did not develop anginal pain during exercise thallium-201 imaging (ST-TL). They were divided into low- and high-risk groups based on results of left ventriculographic findings at rest, ST-TL, and coronary angiography. The incidence of cardiac events was 28/222 (13%) overall, being 9 of 110 (8%) in the low-risk patients, and 19 of 112 (17%) in the high-risk group. Kaplan-Meier survival analysis revealed a significant difference between the two groups (p = 0.020). Analysis of the survival of the high-risk group revealed significant differences between the patients with a negative and positive redistribution (p = 0.047), but such differences were not significant in the low-risk patients. Therefore, the classification of SMI patients into low- and high-risk categories was an appropriate strategy. ST-TL was useful for identifying patients with myocardial ischemia and selecting those to receive coronary revascularization and/or drug therapy.

Adrenergic beta-Antagonists↗