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Biomedical subjects

J Asayama

Publications and source records attributed to J Asayama.

At least 55 records · Page 3Linked to original sources

Effect of cardiac sympathetic nerve stimulation on acutely ischemic myocardium--a comparison with the response to exogenous noradrenaline.

To assess the integrity of an adrenergic nervous function in acute myocardial ischemia, the contractile response of the ischemic region to cardiac sympathetic nervous stimulation (CSNS) was measured in comparison that with to exogenous noradrenaline (NA) infusion. In 13 anesthetized open chest mongrel dogs, haemodynamic changes, segmental wall motion, and the concentration of NA in the efferent coronary vein were measured. CSNS was performed by electrically stimulating the left ansa subclavia. Data concerning baseline values, values during CSNS, and those obtained during NA infusion both before and up to 5 h after coronary occlusion were compared. Regional myocardial blood flow of the ischemic region was also measured using the H+ clearance method. Systolic expansion with coronary occlusion was not changed or augmented by CSNS. However, improvement was observed in all experiments when NA infusion was used. The percent change of systolic shortening, indicating the response of segmental wall motion to CSNS, decreased soon after occlusion, recovered temporarily within 30 min after occlusion, but did not improve throughout the period after 60 min. The decrease of NA overflow into the efferent vein by CSNS showed a biphasic pattern; reduction occurring immediately after occlusion and again 3-5h after occlusion. Throughout these experimental studies it was considered that the preserved responses to the exogenous injected NA represented the contribution of presynaptic factor.

Animals↗

Effects of hypoxia and reoxygenation on regular contractions and postrest contraction in rat papillary muscles.

The effects of hypoxia and reoxygenation on regular contractions and postrest contractions (PRC) of papillary muscle of rats were studied. Isometric tension was measured during two cycles of hypoxia and reoxygenation. Trains of 80 externally continuous stimulations at 40/min were applied. PRCs were evoked by a stimulus train after a 60 sec resting interval. After 90 min of hypoxia (the first hypoxia period), regular contractions and PRCs decreased to 5.6 +/- 2.0% and 23.4 +/- 2.4% of baseline values, respectively (p less than 0.001; n = 18). After 90 min of reoxygenation, the recovery of the PRCs (44.4 +/- 3.4%) was better than that of the regular contractions (23.3 +/- 3.3%) (p less than 0.01; n = 18). After 30 min of hypoxia (the second hypoxic period), regular contractions and PRCs decreased to 2.2 +/- 0.6% and 13.6 +/- 1.6% of baseline values, respectively (p less than 0.001; n = 18). However, the recovery from the second hypoxic injury was not significant for either regular contractions or PRCs. The % diastolic tension, which was normalized to the baseline for regular contractions, increased to 113.2 +/- 6.9% and 133.6 +/- 8.4% at the end of the first and the second hypoxic periods, respectively. There was statistically significant correlation between the % diastolic tension and the % hypoxic injury of PRCs (p less than 0.002; n = 18). There was no significant relationship between % diastolic tension and % hypoxic injury of regular contractions. There was no statistically significant correlation between % diastolic tension and % recovery from the hypoxic injury of either regular contractions or PRCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Electrophysiological effects of sodium channel blockers on guinea pig left atrium.

The electrophysiological effects of five sodium channel blockers (mexiletine, lidocaine, disopyramide, aprindine and flecainide) on the guinea pig left atrium were investigated by recording the action potential and its maximum rate of rise (Vmax). The onset and offset kinetics of use-dependent block of Vmax were analyzed. Lidocaine, aprindine and flecainide were classified clearly as fast, intermediate and slow, respectively. Mexiletine and disopyramide had two components in onset and offset of use-dependent block. Mexiletine showed fast and intermediate kinetics, whereas disopyramide showed intermediate and slow kinetics. Action potential duration at 90% repolarization (APD) was prolonged by disopyramide and mexiletine. The other drugs did not change the action potential duration. Effective refractory period was prolonged by all drugs with relative potency in the following order: disopyramide greater than mexiletine greater than lidocaine greater than aprindine = flecainide. In conclusion, the modes of actions of sodium channel blockers on the atrium were disclosed to be different from those on the ventricle. The pharmacological therapy for atrial arrhythmias should be based on the electrophysiological effects of the drugs on the atrium, not on the ventricle.

Action Potentials↗

[Electrophysiological effect of verapamil on human atrium].

To investigate the effect of verapamil on atrial vulnerability, the following measurements were performed before and after the intravenous administration of verapamil (0.15 mg/kg) in 10 subjects with paroxysmal atrial fibrillation (Paf), and 10 subjects without Paf (non-Paf). During the sinus rhythm, 1) intra-/interatrial conduction time (Intra-/Inter- ACT); the initial deflection of high right atrium (HRA) to that of His bundel/coronary sinus were measured. After 8 consecutive HRA stimuli (A1), premature stimulus (A2) was introduced by shortening the coupling interval (A1A2) and we measured 2) conduction delay zone (CDZ); the zone of A1A2 with the prolongation of Inter-ACT, 3) % maximum atrial fragmentation (%MAF); % maximum value of the ratio of HRA activity width at A2 (Awt) against that at A1 (Awc), 4) fragmented atrial activity zone (FAZ); the zone of A1A2 with % value of Awt/Awc more than 150%,5) repetitive atrial response (RAR); more than 2 atrial activities which occur in response to A2. (6) right atrial effective refractory period (RAERP). Verapamil significantly shortened CDZ and %MFA, slightly lengthened RAERP, and had RAR disappear in Paf, while it did not effect any indices significantly in non-Paf. We concluded that verapamil could reduce atrial vulnerability in Paf due to blocking of atrial conduction delay mediated by slow response fibers.

Adolescent↗

[Effects of ouabain, caffeine, and diltiazem, on spontaneous cyclic Ca2+ release from sarcoplasmic reticulum in the skinned papillary muscles of guinea pigs].

The aim of this study was to assess whether ouabain has a direct action on the sarcoplasmic reticulum (SR) sufficient to be responsible for the mechanism of the inotropic action, and whether caffeine and diltiazem, which inhibit ouabain-induced afterpotential and after-contraction, can inhibit the effects of ouabain on the SR. As one of the functions of SR, spontaneous cyclic contractions (cyclic Ca2+ release from the SR) in saponin-treated skinned fibers of guinea pig papillary muscles were used. Ouabain 10(-9)-10(-7) M increased the frequency of cyclic contractions and induced an incomplete muscle relaxation. Caffeine 1-5 mM and diltiazem 1-5 mM induced a sustained tension. In the fibers treated with ouabain, caffeine and diltiazem induced a sustained tension. In Brij-58 treated skinned fibers, 10(-9) M ouabain did not change the Ca2+ sensitivity of the contractile system. It is now known that ouabain increases intracellular calcium transients. An incomplete muscle relaxation of cyclic contractions seems to be due to both increased SR Ca2+ release and decreased Ca2+ reuptake by SR. Thus, we suppose that ouabain-induced increase in intracellular calcium transients is due to increased intracellular Ca2+, which may be one of the mechanisms in the inotropic action. The masking effects of caffeine and diltiazem on the ouabain-induced increase in cyclic contractions seem to be responsible for the inhibitory effects of drugs on digitalis-induced afterpotential and after contraction.

Animals↗

[Evaluation of coronary arterial stenosis before and after PTCA: visual estimation versus computer-assisted analysis].

Coronary arteriogram of 34 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) were evaluated visually and by computer-assisted analysis, that employed an edge detection method and cine-videodensitometry. The results of visual estimation were in general agreement with those of computer-assisted analysis for determination of percent area of stenosis in severe stenosis, and percent diameter of stenosis in slightly stenotic lesions. Before PTCA, the findings obtained by densitometry agreed with those using the edge detection method. However, after PTCA, the results were significantly different. This discrepancy may have been due to asymmetric morphologic changes in the luminal cross sectional area immediately after PTCA, which could not be assessed by the edge detection method in a single-plane view. Through these studies it was concluded that the densitometry is most useful for evaluating the effects of PTCA.

Absorptiometry, Photon↗

Effect of diltiazem on spontaneous cyclic Ca2+ release from sarcoplasmic reticulum.

We used saponin-treated skinned fibers isolated from papillary muscles of the right ventricle of guinea pigs to compare the effects of diltiazem on the spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum (SR) of cardiac muscle with the effects of caffeine. Both diltiazem and caffeine increased the frequency of cyclic contractions in EGTA (ethyleneglycol-bis-(beta-aminoethylether) N,N,N',N'-tetra-acetate)-free solution and induced an incomplete, concentration-dependent relaxation of the muscle. The results suggest that the spectrum of the pharmacological effects of diltiazem on the SR is similar to that for caffeine, that is diltiazem accelerates the spontaneous Ca2+ release from the SR and suppresses Ca2+ reuptake by the SR, and that diltiazem as well as caffeine may act on the SR in vivo in a specific condition.

Animals↗

Suppressing effects of caffeine on postextrasystolic potentiation in papillary muscles of guinea pigs.

It is well known that the strength of postextrasystolic potentiation (PESP) is dependent on the prematurity of the ectopic beat, though the fundamental mechanism of the potentiation is still obscure. In this study, the effect of a resting interval on the strength of PESP was investigated in isolated papillary muscles of guinea pigs in the presence or absence of caffeine, which inhibits the functions of sarcoplasmic reticulum (SR). PESP of a fixed coupling interval increased and then decreased as the resting interval was prolonged. The maximum of PESP was obtained at a resting interval of 3 to 4 sec. The dependency of PESP on a coupling interval was decreased considerably by 5 x 10(-4) M caffeine and removed completely by 10(-2) M caffeine. Although 5 x 10(-4) M caffeine decreased the degree of contraction of postextrasystole, the maximum contraction of postextrasystole was still obtained at a resting interval of 3 to 4 sec. After the application of 10(-2) M caffeine, the postextrasystolic contraction gradually declined as the resting interval was prolonged. We conclude that SR Ca release contributes largely to a mechanism of PESP and increases in contribution as the coupling interval of an extrastimulation shortens, and that the optimal resting interval is determined by a balance between the activity of SR function and the activity of the sarcolemmal Ca extrusion mechanism.

Animals↗

The effects of an extra-stimulation on post-extra-systolic potentiation in papillary muscle of rats.

The mechanism of post-extrasystolic potentiation (PESP) is unclear. It has previously been suggested that changes in both the calcium release from the sarcoplasmic reticulum (SR) and the transsarcolemmal calcium influx are factors in the development of PESP in guinea-pigs. This experiment investigated the effects of a resting interval and a coupling interval on PESP in rat papillary muscles, which have a well-developed SR. An extra-stimulation was induced at various coupling intervals and a variety of post-extrasystolic intervals were set. The PESP was not dependent on the coupling interval. The post-extrasystolic interval at which the maximal % PESP was obtained was about 90 sec, and post-extrasystolic interval-% potentiation of the PESP relationship curve consisted of an ascending limb and a descending limb. Caffeine eliminated the PESP in a concentration-dependent manner. These findings suggest that SR calcium release plays an important role in the mechanism of PESP in rats. This is consistent with results from guinea-pigs, and implies that the calcium capacity and/or retention of the SR may characterize the post-extrasystolic interval-% PESP relationship in muscle from different species.

Action Potentials↗

[Electrophysiological effects of flecainide acetate on guinea-pig left atrial cells].

Using conventional glass microelectrode technique, electrophysiological effects of flecainide acetate on guinea-pig left atrial muscle fibers were examined. Resting membrane potential was not affected by flecainide at any concentrations tested (10(-7) M-3 X 10(-5) M), although overshoot potential was significantly decreased at the concentration over 3 X 10(-6) M. Effective refractory period significantly increased at 10(-5) M. The reduction of Vmax was about 25% and 50% by 3 X 10(-6) M and 10(-5) M, respectively at 1 Hz. At 3 X 10(-6) M, Vmax decreased by about 10%, 15%, 22%, 33%, and 34% at 0.2, 0.5, 1, 2, and 3 Hz respectively. Flecainide, decreased Vmax of atrial muscle fibers in a dose and frequency dependent manner. It is suggested that flecainide might be effective in the treatment of atrial tachyarrhythmias.

Action Potentials↗

[Value and limitations of stress thallium-201 scintigraphy in evaluating the viability of infarcted myocardial segments].

The aim of this study was to evaluate the value and limitations of stress thallium-201 scintigraphy in evaluating the viability of infarcted myocardial segments following percutaneous transluminal coronary angioplasty (PTCA) and aortocoronary bypass surgery. The relative thallium activity (RTA: the ratio of the count rate in the infarcted segment to that in the intact segment) obtained from delayed images of stress myocardial scintigraphy was used as an index of myocardial viability and was compared with the following parameters. 1) Thallium-201 myocardial perfusion images were made during transient coronary arterial occlusion (PTCA) in eight patients with old myocardial infarction. The RTA of delayed images after successful PTCA was compared with those of stress thallium-201 scintigraphy. There were no significant differences of the RTA between delayed images following PTCA and those of stress myocardial scintigraphy. We therefore, presumed that incomplete redistribution of the delayed images of stress thallium-201 scintigraphy did not truly reflect the degree of coronary stenosis. 2. Regional ejection fraction of the left ventricle after postextrasystolic potentiation (PESP) using equilibrium radionuclide ventriculography was studied in 18 patients with old myocardial infarction, and was compared with the RTA of delayed images of stress myocardial scintigraphy. A significant correlation was observed between the changes in regional ejection fraction by PESP and the RTA three hours after exercise. 3. The RTAs of early and delayed thallium-201 scintigrams were measured at rest in 30 patients with old myocardial infarction, and were compared with the RTA of delayed thallium 201 scintigrams after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

[Long-term follow-up of electrocardiographic changes in patients with asymmetric apical hypertrophy].

The serial electrocardiographic (ECG) changes of 20 patients with asymmetric apical hypertrophy (AAH) were retrospectively reviewed relative to their clinical symptoms, echocardiography and Doppler echocardiography, and thallium-201 perfusion scintigraphy. These patients were followed 4-18 years (mean 8 years). Patterns of the serial ECG changes were as follows: Seven patients (group Ia) had an increase of 10 mm or greater in the highest R wave amplitude in the precordial leads, with newly-developed giant T wave inversion. Five patients (group Ib) had relatively stable ECGs and the changes in the R wave amplitudes of less than 10 mm. Six patients (group IIa) had a decrease of 10 mm or greater in the highest R wave amplitude with mild decreases of negative T wave amplitudes. In the remaining two patients (group IIb) right bundle branch block developed. At the last follow-up study, group IIa had lower R wave amplitudes and longer QTc than did those in group I. The follow-up periods and their mean age did not differ among the groups. At the initial evaluation, exercise limitation was rare in group I; whereas, most of the patients in group II presented symptoms such as palpitation, chest pain or exertional dyspnea. These cardiac symptoms developed slowly but progressively during the follow-up period, and their incidence increased both in groups I and II at the final observation. Left ventricular (LV) wall thickness at the chordal level showed normal values and did not differ between the two groups, but apical wall thickness was greater in group II than in group I. Two-dimensional echocardiography showed a spade-like deformity of the LV in group II. In group I, the LV deformity was less marked and was not noted at the initial examination. Color Doppler echocardiography frequently revealed "paradoxical flow" expelled from the obliterated apex to the base in the early diastolic filling period in group II. Left ventriculography confirmed asynchronous contraction, hyperkinesis in the basal segment and dyskinesis at the apical segment, resulting in this abnormal intraventricular blood flow profiles. Serial studies by thallium-201 (TL) perfusion scintigraphy disclosed that four of the eight patients in group II developed localized hypoperfusion at the apex where a high and homogeneous uptake of TL was previously noted.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Elucidation of reversibility in myocardial injury during hypoxia and reoxygenation in papillary muscles of rats].

We reported the calcium release of sarcoplasmic reticulum (SR) is the major source of activator calcium to postrest contraction (PRC), and that the transsarcolemmal calcium influx is (the major source of activator calcium) to regular contraction in rats. In this study we investigated the combined effects of hypoxia and glucose elimination on PRC and regular contraction. In other words, using papillary muscles of rats, to elucidate the characteristics of reversible or irreversible myocardial injury after ischemia, we investigated the effects of hypoxia on both SR and sarcolemmal functions. After 90 min hypoxia (the first hypoxia-90 min), regular contraction was significantly more reduced than PRC (p less than 0.001; n = 16). With 90 min of reoxygenation, the recovery from hypoxic injury of PRC was better than recovery from injury of regular contraction (p less than 0.01; n = 16). After either 30 min hypoxia (the second hypoxia-30 min) or 60 min hypoxia (the second hypoxia-60 min), regular contraction was also more reduced than PRC, respectively (p less than 0.001; n = 8). However, the recovery from both the second hypoxic injury-30 min and the second hypoxic injury-60 min of PRC was not significantly different from that of regular contraction, respectively (NS; n = 8). Percentages of diastolic tension, which were normalized by baseline regular contraction, increased during hypoxia and decreased incompletely after reoxygenation. After the first reoxygenation of 90 min, 1 microM noradrenaline significantly augmented the magnitude of regular contraction (p less than 0.05; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Different sensitivity of sinus node and atrioventricular node to adenosine triphosphate].

We showed that higher concentration of adenosine 5'-triphosphate (ATP) was required to prolong the spontaneous cycle length of the sinus node (SN) than that required to prolong the spontaneous cycle length of the atrioventricular node (AVN). Spontaneously beating preparations of SN and AVN of rabbit (n = 8) were superfused with Tyrode solution containing 10(-8)-10(-3)M ATP, and action potential was recorded. The negative chronotropic action of ATP was dependent on the concentration. The required concentration of ATP to prolong spontaneous cycle length significantly (p less than 0.01) was 10(-5)M in SN and 10(-6)M in AVN, respectively. At concentrations higher than 10(-6)M, the degree of prolongation was greater in AVN than in SN (p less than 0.01). 10(-7)M dipyridamole enhanced this effect of ATP, while 10(-4)M theophylline reduced it. Action potential duration of 50% repolarization was not changed significantly in either SN or AVN at concentrations up to 10(-3)M. Maximum diastolic potential (MDP) was hyperpolarized from 10(-8)M to 10(-4) M. Hyperpolarization of MDP induced by ATP was greater in AVN than in SN but it was not statistically significant. MDP was depolarized by 10(-3) M ATP in both SN and AVN. The maximum velocity of depolarization was slightly larger in both SN and AVN as the concentration of ATP was increased in the perfusate. However, it was not statistically significant. 10(-3) M ATP decreased the maximum velocity of depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

[Utility of reinjection method in stress Tl-201 myocardial scintigraphy to assess viability of the infarcted myocardium].

To assess viability of the infarcted myocardium, we performed stress Tl-201 myocardial scintigraphy using reinjection method in 37 patients with old myocardial infarction, and in 13 patients of them, Tl myocardial imagings were performed in resting state on the other day within 4 weeks after this examination. In this method, 111 MBq (3 mCi) of thallium was injected at the peak of exercise and initial and delayed images were acquired, then additionally 37 MBq (1 mCi) of thallium was injected after delayed scanning (reinjection) and we obtained post-reinjection images. Delayed images showed redistribution in 15 patients (41%), and no redistribution in 22 patients (59%). In post-reinjection images, 7 (19%) of 15 patients with redistribution and 3 (8%) of 22 patients without redistribution showed improvement of thallium uptake, in total 10 patients (27%) had additional thallium uptake in infarcted regions. And the degree of thallium uptake in post-reinjection images were almost equal to that in resting images. In conclusion, myocardial imaging using thallium reinjection method may be useful for the assessment of viability of the infarcted myocardium.

Female↗

Effect of paced cycle length on sinus node effective refractory period before and after autonomic blockade in patients with sick sinus syndrome.

Effect of basic paced cycle length on sinus node effective refractory period was studied in 22 patients with sick sinus syndrome. Sinus node effective refractory period was measured using three different paced cycle lengths before and after pharmacologic autonomic blockade. Sinus node effective refractory period could be measured at one cycle length, at least, in 59% of the patients before blockade, however, it could be measured at two or more cycle lengths in only 18% of patients because of the chaotic response of sinus node against premature stimuli. It could be measured after pharmacologic autonomic blockade in 68% of the patients at two or more paced cycle lengths. On the other hand, the rest of the patients showed no measurable sinus node effective refractory period at any cycle length, for their sinus node effective refractory periods were shorter than their right atrial effective refractory periods. The comparison of sinus node effective refractory period at different paced cycle lengths was unsuccessful before pharmacologic autonomic blockade, while the refractory period was significantly prolonged as cycle length was shortened after blockade. We concluded that (1) sinus node effective refractory period in humans is prolonged as paced cycle length decreases, (2) the autonomic reflex is the major disturbing factor in measuring sinus node effective refractory period, and pharmacologic autonomic blockade can be usefully employed to eliminate a chaotic sinus nodal response, (3) when sinus node effective refractory period is shorter than right atrial effective refractory period, a shorter paced cycle length should be used for definite measurement of the former.

Adolescent↗

Combined effects of hypoxia and elimination of glucose on resting and postextrasystolic potentiated contractions of papillary muscle of guinea pigs.

We studied the combined effects of hypoxia and the absence of glucose on postextrasystolic potentiated and resting contractions in papillary muscle of guinea pigs. Postextrasystolic potentiations (PESPs) were evoked following trains of 40 externally applied continuous stimulations. During hypoxia resting (regular) contractions decreased to about 25% of baseline tension at 30 degrees C, whereas postextrasystolic potentiated contractions decreased to about 35% of baseline measurement of postextrasystolic potentiated contraction. In contrast, with reoxygenation, PESPs recovered quickly while resting contractions recovered gradually. Caffeine abolished the potentiation of post-extrasystolic contraction not only in normoxia but also in hypoxia. We speculate that calcium release from the sarcoplasmic reticulum (SR) is attributable to PESP for the most part, and that the trans-sarcolemmal calcium influx generally contributes to the steady-state tensions developed by continuous stimulations. In addition, it seems that PESP works in a ischemic heart to compensate for the decreased tension during hypoxia as a potentiation by a premature ventricular contraction. Trans-sarcolemmal calcium influx might be affected more easily than the SR calcium release, by a combination of hypoxia and the absence of glucose, that is, the sarcolemma may be more susceptible to hypoxic injury than the SR.

Animals↗