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Biomedical subjects

I Kubota

Publications and source records attributed to I Kubota.

At least 19 recordsLinked to original sources
PubMed1999

Intracoronary flecainide induces ST alternans and reentrant arrhythmia on intact canine heart: A role of 4-aminopyridine-sensitive current.

BACKGROUND: The electrical alternans shown on an ST segment, ST alternans, is known as one of the most important predictors of ventricular fibrillation (VF). It has also been reported that sodium channel inhibition changes action potential configuration, especially on the repolarization phase. Thus, the sodium channel blocker may produce ST alternans and trigger reentrant arrhythmia. METHODS AND RESULTS: A sodium channel blocker (disopyramide, lidocaine, or flecainide) was infused selectively into the left anterior descending coronary artery in anesthetized, open-chest dogs. Sixty unipolar electrograms were simultaneously recorded from the entire cardiac surface of the heart. The amplitude of ST alternans (STa) was determined as the difference in the ST-segment magnitude between 2 consecutive electrograms. We accepted the greatest STa among 60 leads for evaluation. High-dose flecainide (100 microg. kg-1. min-1) increased STa and evoked a spontaneous VF. The STa in high-dose flecainide loading (8.7+/-3.4 mV; mean+/-SEM) was significantly greater than that in disopyramide or lidocaine (0. 9+/-0.4 and 0.8+/-0.2 mV, P<0.05). Treatment of 4-aminopyridine (4-AP) suppressed the increase in STa and the occurrence of VF evoked by flecainide, while E4031 or verapamil did not inhibit those. CONCLUSIONS: Flecainide caused the ST alternans that was closely correlated to the occurrence of VF. Because the ST alternans was suppressed by 4-AP treatment, a 4-AP-sensitive current such as Ito or Isus may play an important role on this phenomenon.

4-Aminopyridine↗
PubMed1999

Canine model of ventricular fibrillation using programmed stimuli and localized myocardial warming or cooling.

The purpose of this study was to establish an animal model in which ventricular fibrillation (VF) can be induced reproducibly and defibrillation can be accomplished repeatedly. The left anterior descending artery (LAD) was cannulated and perfused with blood from the carotid artery in eleven open-chest dogs. Electrodes of the internal defibrillator were inserted in the cavities of the left atrium and left ventricle via incisions in the left atrial appendage and left ventricular apex. The perfused blood temperature was modulated to produce regional myocardial warming (42 degrees C) or cooling (28 degrees C). In all dogs, VF was repeatedly induced by the combination of warming and left ventricular extrastimuli and by the combination of cooling and right ventricular extrastimuli. The VF was quickly defibrillated by use of the internal defibrillator. The mechanism of VF was found to be reentry by the analysis of activation sequences. This VF model may be useful when evaluating the efficacy of antiarrhythmic drugs because of the high reproducibility.

Animals↗
PubMed1999

Simulation of late potentials and arrhythmias by use of a three-dimensional heart model: casuality of peri-infarctional slow conduction in ventricular fibrillation.

A three-dimensional heart model was constructed to simulate late potentials and ventricular fibrillation (VF). The model consisted of 50,000 discrete elements having a 1.5-mm spatial resolution. Each element represented excitable ventricular tissue, including a conduction system, and was characterized with classical features of the action potential, refractory period, and conduction velocity (theta). An infarcted area on the lateral wall was identified as dead (inexcitable) cells or scar tissue, and peri-infarctional (PI) cells with slow conduction. Body surface potentials were calculated by using the boundary element method. When theta of PI cells was reduced below 0.3 m/s, late potentials became evident after the J point of simulated electrocardiograms (ECGs), and VF was induced by applying four consecutive premature stimuli. However, when Purkinje fibers were removed, VF could not be initiated. Late potentials were induced when slow conduction was present. The presence of PI slow conduction and Purkinje fibers, which were normally contained in the model, was essential for the induction of VF.

Computer Simulation↗
PubMed1998

Muscarinic cholinergic regulation of cardiac myocyte ICa-L is absent in mice with targeted disruption of endothelial nitric oxide synthase.

Cardiac myocytes have been shown to express constitutively endothelial nitric oxide synthase (eNOS) (nitric oxide synthase 3), the activation of which has been implicated in the regulation of myocyte L-type voltage-sensitive calcium channel current (ICa-L) and myocyte contractile responsiveness to parasympathetic nervous system signaling, although this implication remains controversial. Therefore, we examined the effect of the muscarinic cholinergic agonist carbachol (CCh) on ICa-L and contractile amplitude in isoproterenol (ISO)-prestimulated ventricular myocytes isolated from adult mice, designated eNOSnull mice, with targeted disruption of the eNOS gene. Although both eNOSnull and wild-type (WT) ventricular myocytes exhibited similar increases in ICa-L in response to ISO, there was no measurable suppression of ICa-L by CCh in cells from eNOSnull mice, in contrast to cells from WT mice. These results were reflected in the absence of an effect of CCh on the positive inotropic effect of ISO in eNOSnull myocytes. Also, unlike myocytes from WT animals, eNOSnull myocytes failed to exhibit an increase in cGMP content in response to CCh. Nevertheless, the pharmacologic nitric oxide donors 3-morpholino-sydnonimine and S-nitroso-acetyl-cystein increased cGMP generation and suppressed ISO-augmented ICa-L in eNOSnull cells, suggesting that the signal transduction pathway(s) downstream of eNOS remained intact. Of importance, activation of the acetylcholine-activated K+ channel by CCh was unaffected in atrial and ventricular eNOSnull myocytes. These results confirm the obligatory role of eNOS in coupling muscarinic receptor activation to cGMP-dependent control of ICa-L in cardiac myocytes.

Animals↗
PubMed1998

Discordant S-T alternans contributes to formation of reentry: a possible mechanism of reperfusion arrhythmia.

Although a relationship between S-T alternans and life-threatening arrhythmia has been recognized, the mechanism is poorly understood. We examine the role of S-T alternans in the occurrence of ventricular fibrillation (VF) after reperfusion. The left anterior descending coronary artery was occluded for 20 min and then abruptly reperfused in 12 intravenously anesthetized open-chest dogs. Sixty unipolar epicardial electrograms were recorded during the control state, at the end of occlusion, and after reperfusion. The largest magnitude of S-T alternans among 60 leads was defined as the maximum S-T alternans. Isochronal maps of activation time in paced beat and spontaneous ventricular premature contractions (VPC) were analyzed. After reperfusion, VF ensued in six dogs. The maximum S-T alternans augmented progressively with time after reperfusion until VF occurred. In three dogs with VF, when activation of VPC resulted in conduction block and formed reentry, VF ensued. The conduction block was located between sites of discordant S-T alternans (S-T alternans at adjacent leads was out of phase). These data indicate that discordant S-T alternans relates to VF by facilitating the formation of a reentrant circuit.

Animals↗
PubMed1998

Brachial artery flow pattern and clinical backgrounds in patients with angina pectoris.

Blood flow velocity of the brachial artery was measured noninvasively by ultrasound pulsed Doppler technique under the guidance of a B-mode ultrasound image in 56 patients with angina pectoris. There was no significant stenosis along the brachial artery on a B-mode image. The authors investigated seven clinical backgrounds for each patient, ie, age, gender, absence or presence of smoking, hyperlipidemia, diabetes mellitus, hypertension, and the number of significantly stenosed (> or =50%) coronary arteries. Among these variables, the determinants of the brachial artery velocity profile were selected by stepwise multiple regression analysis. Selected variables were the presence of hypertension for peak systolic velocity (R=0.276), age and the number of diseased vessels for peak reverse velocity (R=0.624), and age for peak diastolic velocity (R=0.609). The peak systolic velocity was larger in patients with hypertension than in those without it (0.565+/-0.023 vs 0.490+/-0.013 m/see, P<0.05), and the peak reverse velocity was larger in patients with multivessel disease than those without it (-0.117+/-0.071 vs -0.053+/-0.081 m/sec, P<0.01). Thus, the level of flow velocity of the brachial artery in patients with angina pectoris was partly determined by age, hypertension, and severity of coronary artery disease. The simple measurement of brachial artery flow velocity suggests changes in peripheral vasculature related to atherosclerosis.

Adult↗
PubMed1998

Early mortality after acute myocardial infarction: observational study in Yamagata, 1993-1995.

Although considerable information is available regarding the prognosis after acute myocardial infarction (AMI) in Western populations, little is known about the fate of Japanese subjects after AMI. The purpose of this study was to assess short-term mortality and factors influencing it after AMI in Japan. From April 1993 to December 1995, 1,014 patients with AMI from 41 hospitals in Yamagata Prefecture were registered by cardiologists for the prospective survey. Among patients who died within 28 days after the onset of AMI, immediate causes of death were examined and the clinical profiles of these subjects were compared with those of patients that survived. Early death occurred in 184 patients (short-term mortality 18%). Patients who died were significantly older than survivors (76.1+/-9.4 vs 67.6+/-11.8 years, p<0.01). They were also more likely to be women (50% vs 31%, p<0.01), to have had hypertension (64% vs 54%, p<0.05), diabetes mellitus (29% vs 20%, p<0.02), prior MI (17% vs 12%, p<0.05), or Killip class III or IV disease (63% vs 15%, p<0.01), and were significantly less likely to be current smokers (26% vs 45%, p<0.01) or to have been treated with reperfusion therapy (27% vs 63%, p<0.01). Multivariate logistic analysis demonstrated that independent predictors of early death were Killip class III or IV and advanced age. Reperfusion therapy was a negative predictor of death. Patients who died had arrived at hospital earlier than patients who survived. Mortality as a result of heart failure, cardiac rupture, or arrhythmia fell exponentially after the onset of AMI. Thus, the predictors of short-term mortality were similar to those reported in Western populations. More deaths occurred just after the onset of disease, suggesting that early therapy is important in reducing short-term mortality.

Adult↗
PubMed1998

Decrease in the high frequency QRS components depending on the local conduction delay.

The high frequency components contained in the QRS complex (HF-QRS) are a powerful indicator for the risk of sudden cardiac death. However, it is controversial whether conduction delay increases or decreases the HF-QRS. In 21 anesthetized, open-chest dogs, the right atrium was constantly paced. A cannula was inserted into the left anterior descending artery and flecainide, lidocaine or disopyramide was infused to slow the local conduction. Sixty unipolar electrograms were recorded from the entire ventricular surface and were signal-averaged. Data were filtered (30-250 Hz) by using fast-Fourier transform. The HF-QRS was calculated by integrating the filtered QRS signal. Activation time (AT; dV/dt minimum) was delayed and the HF-QRS was reduced in the area perfused by flecainide, lidocaine or disopyramide. The percent increase in AT closely correlated the percentage decrease in the HF-QRS; the correlation coefficients were 0.75, 0.83 and 0.76 for flecainide, lidocaine and disopyramide infusion, respectively, (p<0.001). Decrease in the HF-QRS linearly correlated with the local conduction delay. This study proved that conduction delay decreases the HF-QRS, and that the HF-QRS is a potent indicator of disturbed local conduction.

Animals↗
PubMed1997

Growth of tracheal autografts in puppies.

The growth of tracheal autografts and the patency of anastomotic regions were studied in 11 mongrel puppies (2.5-4 months of age, 1.9-4.3 kg in weight). Thoracic tracheal autotransplantation of 7 cartilage rings was performed. The tracheal autografts and anastomotic regions were covered with an omental pedicle flap to facilitate revascularization. Seven of the 11 dogs were evaluated for 12 months. The cross-sectional area of the lumen at the center of the tracheal autograft, as measured by thoracic computed tomography (CT), showed a significant increase from 0.37 +/- 0.11 cm2 to 1.13 +/- 0.44 cm2 after 12 months (P < 0.05). At 12 months postoperatively, all of the experimental dogs were killed, their entire tracheas were resected, and the cross-sectional areas of the anastomosis on the proximal and distal sides were measured. The cross-sectional areas at sites 5 mm apart from both anastomoses in the ungrafted trachea were measured as controls. The percent cross-sectional area (%CSA) showed good values of 67.2% +/- 19.6% on the proximal side and 85.1% +/- 12.6% on the distal side. The tracheal autografts appeared both visually and histologically viable 12 months postoperatively. This study was able to demonstrate the growth potential of the tracheal autograft in a growing puppy model.

Age Factors↗
PubMed1997

Effects of activation sequence on monophasic action potential configuration in the dog.

The effects of altered activation sequence on the monophasic action potential (MAP) in in situ beating hearts are not known, although its effects on refractory periods are well documented. In nine anesthetized, open-chest dogs, complete atrioventricular block was produced, and the heart was driven by either right ventricular or left ventricular stimulation. The MAPs of the right and left ventricles were recorded by contact electrodes at cycle lengths of 1,000, 800, 600, and 400 ms. The MAP configuration was evaluated with regard to the difference between phase 1 and phase 2 MAP amplitudes and MAP duration at 50 and 90% repolarization. An MAP recorded from the ventricle that was being electrically stimulated was designated an ipsilateral ventricular stimulation, whereas the MAP recorded from the nonstimulated ventricle was termed a contralateral ventricular stimulation. The difference in amplitude and the 50% and 90% MAP durations for ipsilateral ventricular stimulation were consistently larger than for contralateral ventricular stimulation at all cycle lengths tested. Transient outward current did not appear to play a major role in producing such differences in MAP because intravenous treatment with 4-aminopyridine, a blocker of transient outward current, did not affect the configuration of the MAP. These findings provide an insight on the influence of ventricular activation sequence on the shape of the transmembrane action potential.

4-Aminopyridine↗
PubMed1997

Electrophysiologic effects of sodium channel blockade on anisotropic conduction and conduction block in canine myocardium: preferential slowing of longitudinal conduction by flecainide versus disopyramide or lidocaine.

OBJECTIVES: The purpose of this study was to determine the effects of sodium channel blockade on anisotropic excitation propagation in the intact canine left ventricle. BACKGROUND: Anisotropic ventricular conduction- electric conductivity dependent on the myocardial fiber direction-is one of the important mechanisms of ventricular arrhythmia. However, the effects of sodium channel blockade, especially the differential effect of a subclass of this agent, on the anisotropic properties remain unknown. METHODS: In 28 anesthetized, open chest dogs, a small cannula was inserted into the left anterior descending coronary artery. Saline (control), disopyramide, lidocaine or flecainide was infused selectively into the cannula. An array of 64 epicardial electrodes was placed on the anterior surface of the ventricle. Activation time (AT) was measured along the longitudinal (L) and transverse (T) directions. RESULTS: High dose flecainide (100 microg/kg body weight per min) delayed the AT along the L direction markedly (mean [+/-SE] 227 +/- 38%, p < 0.02) and mildly (121 +/- 10%, p < 0.02) along the T direction in regular beats (p < 0.007, L vs. T). Lidocaine and disopyramide did not show direction-dependent prolongation of the AT on regular beats. When examined on premature beats, AT was delayed, depending on the coupling interval and the fiber direction when saline, flecainide or lidocaine was infused. The conduction blocks along the L direction were observed in three of seven dogs on regular beats after flecainide and ventricular fibrillation ensued in two of these three dogs. CONCLUSIONS: A peculiar slowing of L conduction by flecainide may relate to the character of proarrhythmia.

Animals↗
PubMed1997

Effect of mesenteric venous volatile fatty acids (VFA) infusion on GH secretion in sheep.

The effects of mesenteric venous infusion of acetate, propionate and butyrate mixture (20.3, 40.5 and 81.0 micromol kg[-1] min[-1] over 4 h) on the secretion of GH was examined to investigate the effects of an increase in portal volatile fatty acids (VFA) on GH secretion in relation to inhibition of GH secretion after feeding in sheep. The mesenteric venous infusion at the rate of 40.5 micromol kg(-1) min(-1) increased the portal plasma VFA concentration within the approximate physiological range after feeding. Plasma GH was noticeably suppressed only at the infusion rate of 81.0 micromol kg(-1) min(-1) and the change in the mean concentration from the base line was significantly less than in the control. Although GRF injection rapidly increased plasma GH, the change in the mean concentration from the base line tended to suppress only at the infusion rate of 81.0 micromol kg(-1) min(-1). Plasma FFA was suppressed in a dose-dependent manner after VFA infusion. The change in the mean concentration from the base line was significantly suppressed only at the infusion rate of 81.0 micromol kg(-1) min(-1) relative to the control infusion, but plasma glucose was unchanged by VFA infusion. It is concluded that because the increase in the portal plasma VFA concentration within the range of feeding did not suppress GH secretion, VFA absorbed by the digestive tract may not play a significant role in suppressing GH secretion after feeding in sheep.

Animals↗
PubMed1996

Glibenclamide attenuates peaked T wave in early phase of myocardial ischemia.

OBJECTIVES: ECG peaked T wave appears during the early phase of myocardial ischemia, but the underlying mechanisms remain unknown. The purpose of this study was to elucidate the role of ATP-sensitive K+ channel (KATP) in this ECG change. METHODS: In 12 anesthetized, open-chest dogs, the sinus node was crushed and the right atrium was paced at a cycle length of 400 ms. The left anterior descending coronary artery was abruptly occluded for 60 s before (control) and 15 min after an intravenous infusion of vehicle (n = 6) or glibenclamide (1 mg/kg, n = 6), a blocker of KATP. Forty-eight epicardial electrograms were simultaneously recorded from the anterior surface of the left ventricle. The potentials at 40, 80 and 120 ms from the J point were measured, and these points corresponded to the early, middle and late phases of the T wave, respectively. RESULTS: During the control occlusion, T wave increased time-dependently and the maximal T-wave change was noted at the end of 60 s of coronary occlusion. The extents of T-wave elevation at the early, mid and late T phases were 5.5 +/- 0.5, 7.3 +/- 0.8 and 11.7 +/- 1.8 mV, respectively, and these T-wave elevations were significantly reduced by 33 +/- 21%, 59 +/- 12% and 63 +/- 13%, respectively, after the pretreatment with glibenclamide but not with its vehicle. The % reductions of mid and late T by glibenclamide were significantly larger than that of early T wave (P < 0.05). CONCLUSIONS: An abrupt coronary occlusion accompanied peaked T wave as an early ECG wave change. As the extent of this T-wave elevation was attenuated by glibenclamide, the ischemia-induced alteration of ventricular repolarization can partly (60%) be explained by the modification of KATP activation.

Adenosine Triphosphate↗
PubMed1996

Impaired hyperemic response of brachial artery with the presence of diabetes mellitus in patients with coronary artery disease: a preliminary study.

Microvascular reactivity was assessed in reactive hyperemic response of brachial artery in 10 patients with non-insulin-dependent diabetes mellitus and 34 non-diabetic patients. Each subject was diagnosed clinically as having angina pectoris and was examined by coronary angiography. Brachial arterial flow was determined by a pulsed Doppler velocity measurement, guided by a high-resolution B-mode imaging of the forearm. Peak systolic velocity at the basal state in diabetic and non-diabetic patients was comparable (0.53 +/- 0.03 versus 0.61 +/- 0.04 m/s, respectively; P = NS). The velocity ratio of the peak systolic flow at the basal state to the maximum velocity during hyperemia of 2 min arterial occlusion tended to be less in diabetic than in non-diabetic patients (1.76 +/- 0.14 versus 2.15 +/- 0.13, respectively; P = NS). The duration of hyperemic flow was less in diabetic than in non-diabetic patients (6.7 +/- 0.7 versus 9.9 +/- 0.6 s, respectively; P < 0.02). Such alterations in reactive hyperemia may be relevant to the microvascular disorder of the peripheral vessel in the presence of diabetes mellitus.

Aged↗
PubMed1996

Impaired hyperemic response of forearm vessels in patients with coronary artery disease. A non-invasive evaluation.

The blood flow velocity of the right brachial artery was measured noninvasively by pulsed Doppler flowmetry in 50 patients with angina pectoris. Reactive hyperemia was induced by a 2-minute occlusion of the artery by a tourniquet. We assessed the peak velocity ratio (PVR) and 50% recovery time (RT) which were defined as the ratio of maximal to baseline systolic peak velocity and as the interval from the resumption of arterial flow to 50% decline of the increased systolic peak velocity, respectively. Multiple regression analysis for determinants of PVR and 50% RT was performed with 7 variables which were age, sex, hypertension, diabetes mellitus, smoking, total cholesterol level, and the number of diseased coronary arteries. Multiple R was 0.649 (p < .01) for PVR and 0.682 (p < .01) for 50% RT. There were significant inverse correlations between PVR and the number of diseased vessels (t-value; -3.34), hypertension (-2.43) and smoking (-2.38). The 50% RT was inversely correlated with the number of diseased vessels (t-value; -4.45), feminine gender (-2.75) or smoking (-2.12). Stepwise regression analysis revealed that the number of diseased vessels was the only significant variable for the determination of PVR or 50% RT. An impairment of reactive hyperemia at the forearm vessel correlated with the severity of coronary artery disease in patients with angina pectoris. This finding suggests the presence of some identical mechanisms which are detrimental to both vascular beds. Observation of the hyperemic response at the brachial artery will provide a clue for noninvasive estimation of the extent of coronary artery disease.

Adult↗
PubMed1995

Diagnostic usefulness of activation-recovery interval for reciprocal ECG changes. Effects of regional myocardial cooling, warming, or coronary occlusion on epicardial electrograms in dogs.

The proximal left circumflex coronary artery (LCx) was cannulated and perfused with blood from the carotid artery in nine open-chest dogs. Perfused blood temperature was modulated by immersing a bypass tube in a temperature-controlled water tank. Two epicardial electrodes were placed, one at the LCx area and one at the left anterior descending coronary artery (LAD) area. The temperature of the autoperfused blood was set at 23 degrees C and was gradually elevated to 42 degrees C during 30 minutes. The QRS, ST-T, and QRST areas, and the activation-recovery interval of the electrode at the LCx area, changed unidirectionally in relation to elevation of the blood temperature. Although the QRS, ST-T, and QRST areas of the electrode at the LAD area changed in proportion to changes in the electrode at the LCx area, the activation-recovery interval of the electrode at the LAD area remained constant in all dogs. During 2-minute occlusion of the proximal LCx (n = 7), the activation-recovery interval of the electrode at the LAD area also remained constant despite the presence of reciprocal electrocardiographic changes. The activation-recovery interval is a useful index for defining whether a change in ST-T in a unipolar electrogram is due to a local electrophysiologic effect or a reciprocal effect.

Action Potentials↗