Biomedical subjects

J Asayama

Publications and source records attributed to J Asayama.

At least 37 records · Page 2Linked to original sources

PubMed1993

Effects of pilsicainide on the atrial fibrillation threshold in guinea pig atria. A comparative study with disopyramide, lidocaine and flecainide.

The effects of pilsicainide, a new class Ic antiarrhythmic agent, on the atrial fibrillation threshold (AFT), the atrial effective refractory period (ERP), and the interatrial conduction time (ACT) in Langendorff-perfused guinea pig hearts were investigated. These effects were compared with those of disopyramide, lidocaine and flecainide. Whole guinea pig heart was perfused with Tyrode's solution containing acetylcholine (3 x 10(-7) M). Three indices were measured before and after the administration of the test drugs using right atrial extrastimulus and high frequency stimulation. Pilsicainide, disopyramide and flecainide (> or = 10(-6) M) all significantly increased the AFT. Both pilsicainide and flecainide (> or = 3 x 10(-6) M) significantly prolonged the ERP, but this prolongation was less pronounced than that observed with disopyramide. The ACT was significantly prolonged with pilsicainide (> or = 10(-6) M), and this prolongation was greater than that observed with disopyramide but less than that with flecainide. Lidocaine had no effects on any of the indices measured. In conclusion, pilsicainide had a preventive effect on the atrial fibrillation induced by a combination of acetylcholine and high frequency stimulation in guinea pig hearts, by increasing the atrial ERP and slowing the interatrial conduction. These effects may explain, in part, the clinical effectiveness of this drug on paroxysmal atrial fibrillation.

Animals↗

PubMed1993

Effects of caffeine on ischemia-reperfusion injury in isolated rat hearts.

Cardiac sarcoplasmic reticulum (SR) plays an important role in regulation of the intracellular Ca2+ concentration. It is well known that intracellular Ca2+ overload is one cause of reperfusion injury. Thus, it is predicted that reperfusion injury of myocardium can be prevented by eliminating the Ca2+ overload. This study examined the effects of caffeine, a SR blocker, on reperfusion injury in isolated perfused rat hearts. Working hearts were reperfused for 25 min after 30 or 50 min of ischemia. Caffeine (10(-4) M) was administered during the period of ischemia or the initial 5 min of reperfusion. The left ventricular pressure and the electrocardiogram were recorded. Rate-pressure products were calculated as an index of cardiac function. Adenine nucleotides were measured by high-performance liquid chromatography to assess energy charge. The administration of caffeine for a short period during the initial reperfusion significantly improved cardiac function in the hearts. Caffeine pretreatment during 50 min of ischemia, though, resulted in deterioration of both energy charge and cardiac function. Caffeine did not affect the incidence of either ventricular fibrillation or reversion to sinus rhythm. The energy charges were lower in the preparations with sustained ventricular fibrillation.

Animals↗

PubMed1993

[Frequency dependent prolongation of inter-atrial conduction time by mexiletine in human atrium].

To investigate frequency dependent conduction slowing by mexiletine in the human atrium, we examined inter-atrial conduction time (IACT) at different stimulation frequencies (100/min to 220/min) in 13 patients with paroxysmal atrial fibrillation (Paf) and 7 patients without Paf. IACT was prolonged as the stimulation frequency was increased, and either before or after mexiletine administration IACT was longer in the Paf group (max 114 +/- 9 msec, p < 0.01, mean +/- SD) at any stimulation frequency than in the non-Paf group (max 100 +/- 8 msec). The change in IACT induced by mexiletine administration (% delta IACT) was larger in the Paf group (max 14.8 +/- 5.4%, p < 0.05) than in the non-Paf group (max 5.5 +/- 2.2%) at stimulation frequency over 140/min. Effective refractory period measured at the high right atrium was slightly decreased due to mexiletine in both the non-Paf and the Paf group. In conclusion, mexiletine showed frequency dependent suppression of conduction in the human atrial myocardium especially in patients with Paf.

Adolescent↗

PubMed1993

[Effects of propafenone on the parameters of body surface electrocardiogram in comparison with those of disopyramide].

The purpose of this study is to investigate the clinical effects of propafenone on the QT(QTc), QRS, PQ and RR interval of body surface electrocardiogram (ECG) in comparison with the effects of disopyramide. In 10 patients (5 with paroxysmal atrial fibrillation and 5 with ventricular premature complex: ages 48-77), after 4 days' observation without any cardioactive drugs, disopyramide (300mg/day) was administered orally for 7 days. After discontinuing the administration of disopyramide, 4 more days were allowed to wash out the drug, and propafenone (450mg/day) was administered orally for 7 days. 12-lead ECG was taken twice before the administration of disopyramide (Pre-1 and -2), on the 1st, 3rd, 5th and 7th days after the administration of disopyramide. Then it was also taken on the day before the beginning of propafenone administration and on the 1st, 3rd, 5th and 7th days after the administration of propafenone. The corrected QT (QTc = QT/square root of RR), QRS, PQ and RR intervals in lead II or V2 of each ECG were measured as the mean value of 5 consecutive sinus beats. The control values of QTc, QRS, PQ and RR intervals were calculated as the mean values of Pre-1 and -2, and the other values were expressed as the % ratio to the control values. Propafenone hardly altered the QTc interval but prolonged QRS interval after the 5th day of administration (110 +/- 12%, p < 0.05), while disopyramide significantly prolonged the QTc interval after the 3rd day of administration (109 +/- 5%, p < 0.001) without affecting the QRS interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

[Two cases of anomalous origin of coronary artery from non-coronary sinus of valsalva identified by transesophageal echocardiography].

A 36-year-old male (case-1) and a 54-year-old female (case-2) were admitted to our hospital because of chest oppression on effort. Exercise electrocardiograms of both patients revealed significant ST segment depression in leads II, III, aVF and V5-6. Coronary angiograms demonstrated an anomalous origin of the left circumflex coronary artery in case-1 and an anomalous origin of the right coronary artery in case-2. Furthermore transesophageal echocardiography (TEE) revealed that both anomalous coronary arteries were running from the non-coronary sinus of Valsalva. The anatomical relation between the anomalous coronaries running from non-coronary sinus of valsalva and the great vessels was directly detectable by TEE. Although these cases are very rare, TEE is useful for the assessment of this type of coronary anomaly.

Adult↗

PubMed1993

[Effect of pilsicainide hydrochloride on atrial fibrillation threshold].

To inventigate the electrophysiologic effects of pilsicainide hydrochloride on atrial fibrillation, we compared atrial fibrillation threshold (AFT), right atrial effective refractory period (RAERP), and inter-atrial conduction time (Inter-ACT) before and after the administration of pilsicainide in 12 patients with lone paroxysmal atrial fibrillation. The following electrophysiologic study was performed before and after the administration of the drug as the paced cycle length of 500msec. First, RAERP was measured. Secondly, Inter-ACT from the stimulating artifact to the initial deflection in the elecrocardiograms of the coronary sinus was measured. Thirdly, high-frequency (50Hz) stimulation was given at right atrial appendage continuously for one second just after the eighth basic paced beat. The stimulation current was increased by 1mA in a stepwise fashion from 2mA until atrial fibrillation ensued. AFT was defined as the lowest intensity of the current that induced atrial fibrillation or flutter of more than 30 seconds. Pilsicanide significantly increased AFT and Inter-ACT, but did not change RAERP. In conclusion, it is suggested that pilsicainide might decrease atrial vulnerability mainly by its effect on inter-atrial conduction delay and by the resulting increase in AFT.

Adult↗

PubMed1993

[A case of stunned myocardium: dual SPECT findings similar to acute myocardial infarction (AMI)].

Emergent cardiac catheterization was performed on a 70-year-old female patient who was admitted for further evaluation of acute myocardial infarction. Coronary angiography didn't reveal any significant stenotic lesion, but levogram showed extensively abnormal contractility around the center of the apex region. On the second hospital day, 99mTc-PYP/201TlCl dual SPECT gave findings similar to those found in acute myocardial infarction, but myocardium--released enzyme stayed within the normal range. Two weeks after, 201TlCl myocardial scintigraphy showed disappearance of the perfusion defect, and normal contractility was observed on the levogram of the chronic phase. Since this case was clinically denied to be myocardial infarction, it was considered a typical case of stunned myocardium which showed prolonged left ventricular abnormal contractility with transient myocardial ischemia. This is a case suggestive for estimations of myocardial reversibility in patients with myocardial perfusion and metabolic disorder in dual SPECT.

Aged↗

PubMed1992

Acute effects of doxorubicin on skinned cardiac muscle fibres of guinea pigs.

OBJECTIVE: The aim was to examine the effect of doxorubicin on spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum of skinned fibres, as measured by isometric tension development in EGTA free, Ca2+ free solution. METHODS: Experiments were done on fragments of papillary muscles from the right ventricles of guinea pigs. Skinned fibres were prepared by treatment with saponin. The effects of doxorubicin in concentrations of 2 x 10(-9) to 2 x 10(-5) M on cyclic contractions were evaluated in 20 muscles. The effects of doxorubicin in concentrations of 2 x 10(-7) and 2 x 10(-5) M on pCa-tension relation were examined in 14 muscles treated with Brij-58. RESULTS: Doxorubicin (2 x 10(-9) to 2 x 10(-5) M) increased the frequency of cyclic contractions and induced an incomplete muscle relaxation in a dose dependent manner. Doxorubicin 2 x 10(-7) M had no effect on pCa-tension relation. Doxorubicin 2 x 10(-5) M shifted the pCa-tension curve slightly to the left. CONCLUSIONS: An incomplete muscle relaxation is considered to be due to an increase in Ca2+ release from the sarcoplasmic reticulum and a slight increase in the sensitivity of the contractile proteins to Ca2+. These observations suggest that one cause of the intracellular Ca2+ overload induced by doxorubicin, a putative mechanism of the doxorubicin induced cardiomyopathy, is attributable to the direct effects of doxorubicin on the sarcoplasmic reticulum, impairing its ability to sequester Ca2+.

Animals↗

PubMed1992

Slow kinetic property of mexiletine in guinea pig atrium.

We studied the onset and offset of use-dependent block (UDB) of maximum rate of rise of action potential (Vmax) with 3 x 10(-5)M mexilietine in guinea pig left atrium. A large decrease of Vmax was observed between the first and the second excitation when the preparations were stimulated at 4Hz after two minutes of rest period. UDB after the second excitation developed slowly to reach steady state within 30 sec. These two onset rates were 1.016 +/- 0.055 and 0.070 +/- 0.009/action potential. Recovery process was also fitted with two exponential equations. The time constant of the fast recovery was 528 +/- 23 msec. and the slow one was 3099 +/- 435 msec. The relative contribution of the slow component was 38.3 +/- 2.6% in the onset and 29.7 +/- 3.1% in the recovery. In spite of elevated maximum diastolic potential at 4 Hz stimulation, the relationship between resting membrane potential and Vmax disclosed voltage-dependent block of Vmax was no more than 5%. It is concluded that mexiletine has a slow kinetic component as well as a fast one. When atrial muscle is depolarized, Vmax decreases further. Therefore, mexiletine may be more effective against the atrial arrhythmias than predicted previously.

Action Potentials↗

PubMed1992

Acute and subacute effects of doxorubicin on postextrasystolic potentiation in guinea pig papillary muscles.

To investigate the effects of doxorubicin on postextrasystolic potentiation (PESP), isolated guinea pig papillary muscles were field-stimulated and the resulting isometric force was recorded. Postextrasystolic contraction was evoked following trains of 37 regular stimulations. The effects of acute doses of doxorubicin (0.2 mM) on regular contractions and postextrasystolic contractions were examined for 2 hr. The effects of subacute doses of doxorubicin (total dose 5 mg/kg intraperitoneally) on the relationship between %PESP (postextrasystolic/regular contraction) and both the extra-stimulus coupling interval and the postextrasystolic interval were examined. Acute administration of doxorubicin decreased the amplitude of postextrasystolic contractions more than that of regular contractions. Thus, %PESP in the doxorubicin-treated group decreased significantly over time. There was no similar decrease in the control papillary muscles. Both the extra-stimulus coupling interval and the postextrasystolic interval had less of an effect on %PESP in doxorubicin-treated animals than in control animals. Since PESP depends upon sarcoplasmic reticulum activity, our results indicate that acute and subacute exposure to doxorubicin impairs the activity of the sarcoplasmic reticulum of guinea pig papillary muscles.

Animals↗

PubMed1992

Disuse atrophy of the left ventricle in chronically bedridden elderly people.

In the elderly cardiac size and function are determined by their level of physical activity. In this study, we assessed by echocardiography, the anatomic and physiologic changes of the heart in 28 elderly patients who had no cardiac disease and who were chronically bedridden. The data obtained were compared to those obtained from a control group of 38 age and sex matched elderly people whose activities had not been restricted. Chronically bedridden patients had markedly smaller left ventricular dimensions in both end-diastole and end-systole and smaller left atrial dimensions than did control subjects (3.7 +/- 0.7 vs 4.7 +/- 0.6 cm, p less than 0.001, 2.4 +/- 0.8 vs 2.9 +/- 0.7 cm, p less than 0.02 and 3.2 +/- 0.5 vs 3.8 +/- 0.9 cm, p less than 0.01, respectively). Though the wall thickness of the interventricular septum did not differ between the study groups, the left ventricular posterior walls of the bedridden group were significantly thinner than in the control group (0.8 +/- 0.2 vs 1.0 +/- 0.2 cm, p less than 0.01). The bedridden group had a significantly lower stroke index (26.9 +/- 6.2 vs 47.0 +/- 11.1 ml/m2, p less than 0.001) and cardiac index (1.84 +/- 0.52 vs 3.15 +/- 0.63 l/min/m2, p less than 0.001) than did the control group. Left ventricular mass index and left ventricular systolic stress were significantly lower in bedridden patients than in control subjects (88.0 +/- 18.1 vs 143.5 +/- 30.9 g/m2, p less than 0.001, and 135.9 +/- 4.9 vs 186.6 +/- 35.7 10(3) dynes/cm2, p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Effects of reduction of contractile work on mechanical function in post-hypoxic guinea pig papillary muscles and on myocardial energy metabolism in post-ischemic rat hearts.

This study was designed to investigate effects of quiescence by cessation of electrical stimulation during the first stage of reoxygenation on recovery of mechanical function from hypoxia-induced contractile dysfunction in papillary muscles and effects of the absence of cardiac output on myocardial energetic metabolism of post-ischemic hearts. (1) Regular contractions and postextrasystolic contraction were evoked. After 120 min hypoxia, muscles were reoxygenated. In muscles of quiescence during the first 30 min reoxygenation, the recovery of regular contractions was better than that in muscles in which programmed stimulation was continued. However, the quiescence had no effect on the recovery of post-extrasystolic contractions from hypoxia-induced contractile dysfunction. (2) Isolated hearts were perfused either according to Langendorff technique or as working heart preparations. After 40 min ischemia, hearts were reperfused for 25 min. Although there was no difference in energy charge of myocardium between 2 modes of reperfusion, % incidence of sustained ventricular fibrillation in muscles in which non-working mode was maintained for the first step of reperfusion was lower than that in which working mode was continued. We presume that the reduction of contractile work during the initial step of reperfusion is of value for cardio-protection.

Animals↗

PubMed1992

Effects of hypoxia and reoxygenation on steady-state and potentiated contractions in papillary muscle of guinea pigs.

We studied the effects of hypoxia and reoxygenation on steady-state contractions and potentiated contractions of papillary muscles of guinea pigs. Isometric tension was measured while 120 min periods of hypoxia and reoxygenation were repeated twice. Reoxygenation after the first period of hypoxia induced a gradual recovery in steady-state contractions and a rapid recovery in potentiated contractions from the first hypoxia-induced contractile depression. After the second period of hypoxia, steady-state and potentiated contractions decreased progressively. During the second period of reoxygenation, the recovery of steady-state and potentiated contractions was very poor and the marked elevation of diastolic tension did not decrease. There were no good correlations between hypoxic depression just before reoxygenation and the recovery of both potentiated contraction and steady-state contraction at 120 min of reoxygenation. The recovery from the hypoxia-induced depression was poor in the preparations with marked elevation in diastolic tension. From these findings, we conclude that hypoxia-induced depression is progressively worsened by an additional episode of hypoxia and that diastolic tension is one of the determinants of the low contractile level achieved by steady-state and potentiated contractions in the severely hypoxic state. The degree of hypoxia-induced depression does not determine redevelopment of force with reoxygenation.

Animals↗

PubMed1992

[Extent and degree of coronary flow reserve in hypertrophic cardiomyopathy assessed by delta Fract map unfolding coronary flow reserve index].

Patients with hypertrophic cardiomyopathy (HCM) are known to have ischemic events and decreased coronary flow reserve, but the variabilities in the site and degree of fall between patients with this disease have not been clarified. To elucidate these variabilities, we performed exercise myocardial single photon emission computed tomography (SPECT) using double dose method in 30 patients with HCM (6 with obstruction, 17 with non-obstruction, 7 with apical hypertrophy) and 10 normals. Then, the delta Fract (coronary flow reserve index) map was obtained for each subject. Exercise and then rest Tl-201 myocardial scintigraphy were performed after administration of Tl-201. The data were reconstructed, making the circumferential curves from the same level of short-axis imaging during exercise and at rest. By subtracting the values at rest from the values during exercise, which were divided by the values at rest, delta Fract in each frame was obtained, and described on the unfolded map. The extent and degree of coronary flow reserve were visually estimated by this delta Fract map. Patients were categorized into 5 groups: diffuse fall of coronary flow reserve (D-type), 6 cases; localized fall of the septum or lateral wall (L-type), 5 cases; fall of apical region (A-type), 5 cases; mild fall (M-type), 6 cases; and normal pattern (N-type), 8 cases. We concluded that delta Fract map is useful for evaluating the extent and degree of coronary flow reserve in HCM.

Adult↗

PubMed1992

Effect of manidipine on cardiac hypertrophy and coronary circulation in DOCA/salt hypertensive rats.

The effect of manidipine on cardiac hypertrophy, coronary circulation, left ventricular weight and maximal coronary flow in hypertension was measured in DOCA/salt treated systolic hypertensive rats with and without manidipine treatment. Normotensive rats were used as controls. After feeding with 0.05% manidipine-containing food, blood pressure was reduced only in DOCA/salt hypertensive rats, but not in control rats. After 3 weeks of treatment, sodium excretion was significantly increased in DOCA/salt-treated rats with or without manidipine treatment. Hearts were removed and perfused with modified Krebs-Henseleit solution with adenosine (5 x 10(-5) M) in a Langendorff apparatus. Maximal coronary flow (MCF) was significantly decreased only in DOCA/salt hypertensive rats without treatment, while manidipine treatment restored MCF. Left ventricular weight/body weight was also markedly greater in DOCA/salt-treated rats not given manidipine. Left ventricular weight in DOCA/salt-treated rats given manidipine was significantly reduced compared with DOCA/salt hypertensive rats without treatment, although it was heavier than in the control animals. Morphological examination showed that the increased wall/lumen ratio in DOCA/salt hypertensive rats was reduced by manidipine treatment. These findings suggest that treatment with manidipine in DOCA/salt hypertensive rats lowered high blood pressure and improved impaired coronary circulation with a reduction in left ventricular and vascular hypertrophy.

Aldosterone↗

PubMed1992

[Electrophysiologic effects of flecainide on guinea pig atrium].

We investigated the effects of flecainide on guinea pig atrial muscle. Using Langendorff's method, the whole heart of a guinea pig was perfused with Tyrode's solution containing acetylcholine (3 x 10(-7) M). Then, with right atrial extrastimulus and high frequency pacing method, the following values were measured before and after administration of flecainide (10(-7)-10(-5) M). A) Effective refractory period (ERP); the longest coupling interval which failed to produce right atrial activity at premature stimulus. B) Interatrial conduction time (ACT); After right atrial stimuli by trains at PCL 200 ms for 5 min the interval from the stimulation to the first deflection of the left atrial activity. C) Atrial fibrillation threshold (AFT); the minimal amount of current required to induce atrial fibrillation lasting for more than 30 sec by 50 Hz high frequency stimulation. Flecainide lengthened ERP (> or = 3 x 10(-5) M) and ACT (> or = 10(-7) M). Flecainide (10(-5) M) significantly increased AFT which correlated well with ERP (r = 0.81, p < 0.002) and ACT (r = 0.84, p < 0.002). In conclusion these effects of flecainide on guinea pig atrium might explain in part the clinical effectiveness of the drug on paroxysmal atrial fibrillation.

Animals↗

PubMed1992

[Electrophysiologic study of cibenzoline in patients with paroxysmal atrial fibrillation with special reference to atrial fibrillation threshold].

Electrophysiologic effects of cibenzoline were studied in 7 patients (6 males and one female) aged from 40 to 69 years (mean +/- SD; 52 +/- 10) with paroxysmal atrial fibrillation which was documented by 12 leads ECG or by 24 hours Holter monitoring. No organic heart diseases were found except in one patient with dilated cardiomyopathy and sick sinus syndrome (SSS). Cibenzoline (200mg) given orally increased P wave duration, PR interval and QRS duration significantly. The duration of P wave was gradually increased as the pacing frequency was increased. Neither sinus cycle length, nor sinus node recovery time (SRT), nor Wenkebach cycle length, nor atrial effective refractory period, nor QT interval was changed by the drug. One patient with SSS showed increase in SRT from 2,303 msec to 5,150 msec. The minimum current which was required to induce atrial fibrillation by rapid atrial stimulation (50 Hz, 1 sec) lasting more than 30 sec was defined as atrial fibrillation threshold (AFT). The AFT was 4.0 +/- 2.2 mA at the baseline state in 7 patients. After the oral administration of cibenzoline, 5 patients showed increase in AFT, while 1 patient showed decrease and another patient showed no change in AFT. Statistically, AFT was significantly increased to 7.3 +/- 3.4 mA in 7 patients. The results suggest that cibenzoline might be effective to prevent paroxysmal atrial fibrillation in patients without organic heart diseases.

Administration, Oral↗

PubMed1991

Prolonged atrial activity due to delayed conduction in the atrium of patients with paroxysmal atrial fibrillation.

We investigated the relationship between the duration of electrical atrial activity and intra-atrial conduction time to determine whether the prolonged atrial activity was due to delayed conduction in the human atrium. The study included 15 patients with paroxysmal atrial fibrillation (PAF) and 15 control patients. The duration of atrial electrical activity was measured by selecting a minimum electrographic amplitude of 50 microV. In patients with PAF, the duration of atrial activity was prolonged in proportion to the delay of interatrial conduction time from the high right atrium to the coronary sinus as the coupling interval of premature extrastimuli was decreased. Both the fragmented atrial activity zone and the interatrial conduction delay zone were wider in patients with PAF than in control patients. It is concluded that assessment of the duration of atrial activity with a minimum amplitude of 50 microV is useful in evaluating human atrial vulnerability since it reflects the atrial conduction delay in patients with PAF.

Adolescent↗