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Koichiro Yoshioka

Publications and source records attributed to Koichiro Yoshioka.

8 recordsLinked to original sources
PubMed2006

Heavy ion radiation up-regulates Cx43 and ameliorates arrhythmogenic substrates in hearts after myocardial infarction.

OBJECTIVE: Radiation has been shown to enhance intercellular communication in the skin and lungs through an increase of connexin43 (Cx43) expression. If analogous Cx43 up-regulation is induced in the diseased heart, it would provide a new perspective in radiation therapy for arrhythmias. The aim of the present study is to test this hypothesis. METHODS: Non-transmural myocardial infarction (MI) was created in 24 rabbits by microsphere injection into the coronary arteries. Twenty-four rabbits without MI were used as controls. Targeted external heavy ion beam irradiation (THIR; 15 Gy) was applied 2 weeks after MI with an accelerator (HIMAC, Chiba, Japan). RESULTS: The THIR was associated with an increase of Cx43 mRNA and protein levels in the left ventricle in control as well as in MI rabbits. THIR also increased lateralization of Cx43, which was no longer colocalized with cadherins. In MI hearts, immunoreactive Cx43 signals were reduced in the peri-infarct zone, and the reduction was reversed by THIR. In-vivo epicardial potential mapping on the free wall (64 unipolar electrodes to cover 7 x 7 mm) in MI hearts revealed reduced conduction velocity, whereas dispersion of the activation-recovery interval (ARI) was increased compared with controls, and these changes were reversed by THIR. The vulnerability for ventricular tachyarrhythmias (VT/VF), which was estimated by programmed stimulation, was increased in MI hearts, and this increased vulnerability to arrhythmias was reversed by THIR. CONCLUSIONS: THIR increases Cx43 expression, improves the conductivity, decreases the spatial heterogeneity of repolarization, and reduces the vulnerability of rabbit hearts to ventricular arrhythmias after MI. THIR could have an antiarrhythmic potential through an improvement of electrical coupling.

Animals↗
PubMed2006

Nifekalant hydrochloride administration during cardiopulmonary resuscitation improves the transmural dispersion of myocardial repolarization: experimental study in a canine model of cardiopulmonary arrest.

BACKGROUND: Because nifekalant hydrochloride (NIF) displayed a superior defibrillating effect on ventricular tachycardia/fibrillation (VT/VF) in cardiopulmonary arrest (CPA) patients, despite some QT prolongation, its effect on transmural dispersion of repolarization (TDR) in the left ventricle (LV) in an animal model of CPA was investigated. METHODS AND RESULTS: Eight beagle dogs were created with a myocardial infarction under anesthesia, and then VT/VF induction by continuous stimulation and cardiopulmonary resuscitation (CPR) were repeated. NIF (0.3 mg/kg) was administered under acidotic conditions (pH 7.26). The QTc interval measured by Y-lead ECG showed no significant prolongation before and after NIF. The activation recovery interval (ARI) measured by 64-lead LV surface mapping showed minimum ARI prolongation (40%) by NIF without maximum ARI prolongation, and as a result the ARI dispersion decreased by 67%. The repolarization time (RPT) with the plunge electrode showed 13-19% prolongation in the subendocardium and subepicardium with CPR, but NIF prolonged the RPT in the middle layer alone (17%), and as a result Plunge-TDR decreased by 82% (n=8, p<0.05). CONCLUSIONS: Administration of NIF during CPR decreased the TDR by RPT prolongation selectively in the middle layer. Because the subendocardial and subepicardial RPTs after CPR were already prolonged before NIF administration, it may have been the reason why the QT-prolonging effect of NIF was not reflected in the body surface ECG.

Animals↗
PubMed2006

Can nifekalant hydrochloride be used as a first-line drug for cardiopulmonary arrest (CPA)? : comparative study of out-of-hospital CPA with acidosis and in-hospital CPA without acidosis.

BACKGROUND: Early defibrillation of ventricular tachycardia and fibrillation (VT/VF) is an urgent and most important method of resuscitation for survival in cardiopulmonary arrest (CPA). We have previously reported that nifekalant (NIF), a specific I(Kr) blocker developed in Japan, is effective for lidocaine (LID) resistant VT/VF in out-of-hospital CPA (OHCPA). However, little is known about the differences in the effect of NIF on OHCPA with acidosis and in-hospital CPA (IHCPA) without acidosis. METHODS AND RESULTS: The present study enrolled 91 cases of DC shock resistant VT/VF among 892 cases of CPA that occurred between June 2000 and May 2003. NIF was used (0.15-0.3 mg/kg) after LID according to the cardiopulmonary resuscitation (CPR) algorithm of Tokai University. The defibrillation rate was higher in the NIF group for both OHCPA and IHCPA than for LID alone, and the VT/VF rate reduction effect could be maintained even with acidosis. However, sinus bradycardia in OHCPA, and torsades de pointes in IHCPA were occasionally observed. These differences in adverse effects might be related to the amount of epinephrine, serum potassium levels, serum pH, and interaction with LID. CONCLUSIONS: NIF had a favorable defibrillating effect in both CPA groups, and it shows promise of becoming a first-line drug for CPR.

Acidosis↗
PubMed2005

Combined effects of nifekalant and lidocaine on the spiral-type re-entry in a perfused 2-dimensional layer of rabbit ventricular myocardium.

BACKGROUND: Spiral re-entry plays the principal role in the genesis of ventricular tachycardia and ventricular fibrillation (VT/VF). The specific I(Kr) blocker, nifekakant (NIF) has, often in combination with lidocaine (LID), recently been used in Japan to prevent recurrent VT/VF, but the combined effects of these drugs on spiral re-entry had never been investigated. METHODS AND RESULTS: A ventricular epicardial sheet was obtained from 13 Langendorff-perfused rabbit hearts by means of a cryoprocedure, and epicardial excitations were analyzed with a high-resolution optical mapping system. Nifekakant (0.5 micromol/L) caused significant prolongation of action potential duration (APD) and LID (3 micromol/L) attenuated the APD prolongation without affecting the conduction velocity. VT were induced in 6 hearts by cross-field stimulation, and single- or double-loop spirals circulating around variable functional block lines were visualized during the VT. Nifekakant reduced VT cycle length and caused early termination in association with destabilization of the spiral dynamics (prolongation of functional block line, frequent local conduction block, and extensive meandering). These modifications of spiral-type re-entrant VT by NIF were prevented by addition of LID. CONCLUSIONS: The effects of NIF on the spiral excitations are reversed by LID. This interaction should be taken into account when these drugs are used in combination to treat VT/VF.

Animals↗
PubMed2005

Clinical profile and prognosis of hospitalized patients with congestive heart failure in Isehara, Japan.

Since the clinical profile and prognosis of heart failure depending on time of the study performed, regional characteristics of background population and different race, we attempted to evaluate the prognosis of symptoms and life expectancy of Japanese patients with heart failure. We evaluated the clinical profiles and prognoses of 1,015 consecutive patients with congestive heart failure (CHF) for whom hospitalization was required. A total of 1,015 consecutive CHF patients (584 males and 431 females) were enrolled in this study, however the total number of events investigated was 1,409. Of these patients, survival was confirmed in 413 patients, death was confirmed in 299 patients, and the prognoses of 303 patients remained unknown due to transfer to other hospitals or for some other reasons. The mean age on admission was 68.4 +/- 14.9 years. In both males and females, the peak age at the onset of CHF was in the seventies, and for patients in their eighties, the number of female patients with CHF was larger than that of male patients. Major underlying heart diseases consisted of ischemic heart disease (34%), valvular heart disease (22%), dilated cardiomyopathy (11%), and hypertension (10%). Most CHF patients who had dilated cardiomyopathy as an underlying disease were hospitalized several times, and 45% of them were hospitalized 3 times or more. The life expectancy of patients with CHF caused by ischemic heart disease was the poorest, and their 5-year and 10-year survival rates were 55% and 38%, respectively. Similarly, 5-year and 10-year survival rates of patients with CHF caused by valvular heart disease, hypertension, and dilated cardiomyopathy were 62% and 44%, 58% and 53%, and 70% and 65%, respectively. In 299 deceased patients, the mean age at death was 72.2 +/- 13.9 years. In all these deceased patients, direct causes of death were sudden death (16.1%), CHF (42.2%), others (31.4%), and unknown (10.4%). The frequency of sudden death was highest (25%) in patients with CHF caused by dilated cardiomyopathy, followed by those with CHF caused by valvular heart disease (18%) and those with CHF caused by ischemic heart disease (17.5%). In addition, the frequency of death from CHF was highest (60%) in those with CHF caused by dilated cardiomyopathy, followed by those with CHF caused by ischemic heart disease (49.2%).

Adolescent↗
PubMed2003

[Efficacy of Nifekalant hydrochloride for life-threatening ventricular tachyarrhythmias in patients with resistance to lidocaine: a study of patients with out-of-hospital cardiac arrest].

OBJECTIVES: Class I antiarrhythmic agents are not always effective in the treatment of life-threatening ventricular tachycardia/ventricular fibrillation (VT/VF) especially in patients with cardiopulmonary arrest. Nifekalant hydrochloride(NIF) is a novel class III antiarrhythmic agent for malignant VT/VF. This study prospectively evaluated NIF efficacy for life-threatening VT/VF observed after cardiopulmonary arrest. METHODS: Thirty-two of 145 patients who were transferred to the emergency room in Tokai University Hospital showed VT/VF after resuscitation from cardiopulmonary arrest from June 2000 to March 2001. These 32 patients were treated with 12 mg (mean) epinephrine and 1.0-2.0 mg/kg lidocaine following direct current application(200 to 360J), and then classified into two groups. Eleven patients received intravenous 0.15 to 0.3 mg/kg NIF followed by intravenous infusion of 0.3 to 0.4 mg/kg/hr NIF(NIF group). The other 21 patients received 1.0 to 2.0 mg/kg of lidocaine(non-NIF group). RESULTS: Sinus rhythm was restored in the nine patients(82%) in the NIF group but only four patients (19%) in the non-NIF group. QTc was not prolonged(0.45 +/- 0.04 sec, n = 9) and no torsades de pointes was observed in the NIF group. Two patients survived but the remaining nine patients died in the NIF group. Five patients died of cardiac standstill following sinus bradycardia and repeated sinus arrest within 2 to 27 hr after admission, two patients died of sudden cardiac arrest from sinus rhythm, and two patients died of persistent VT/VF. In contrast, all 21 patients in the non-NIF group died. Seventeen patients died of persistent VT/VF before hospitalization, one patient died of recurrent VT/VF, and three patients died of cardiac standstill following sinus bradycardia. CONCLUSIONS: NIF effectively suppresses VT/VF which is refractory to direct current shock in patients with cardiopulmonary arrest. However, NIF may rather worsen electrophysiological function in the sinus node after administration of high doses of epinephrine, and may induce sinus bradycardia and/or sinus arrest. Careful observation, such as monitoring of electrocardiography and blood pressure and temporary cardiac pacemaker use, is needed to prevent death in patients surviving after cardiopulmonary arrest if NIF is administered following high dose epinephrine infusion.

Adult↗