Tadashi Hashida

Impact of vascular remodeling on the coronary plaque compositions: An investigation with in vivo tissue characterization using integrated backscatter-intravascular ultrasound

Recent studies have indicated that positive remodeling is strongly associated with development of acute coronary syndrome (ACS). The aim of this study was to compare plaque composition of vascular remodeling patterns by an established in vivo tissue characterization method using integrated backscatter (IB)-intravascular ultrasound (IVUS). The study population consisted of 41 consecutive patients who received IVUS prior to percutaneous coronary intervention. Remodeling index (RI) was calculated as the external elastic membrane (EEM) area at the minimal lumen area (MLA) site divided by average EEM area at the proximal and distal reference sites. The patients were divided into two groups based on RI: positive remodeling (PR) defined as RI>1 and non-PR as RI<or=1. A total of 21 areas centered at MLA per lesion site were evaluated by IB-IVUS at 1mm intervals. The occupancy rate of four tissue types within atherosclerotic plaques was compared between the two groups. Percent lipid volume in the PR group (n=20) was significantly greater than the non-PR group (n=21) (40.5+/-14.8% vs. 26.4+/-15.9%, p<0.001). In contrast, % fibrous volume in the PR group was significantly lower than the non-PR group (49.9+/-9.4% vs. 56.1+/-9.6%, p=0.042). Percent dense fibrous volume and % calcified volume were slightly but significantly lower in the PR group compared with the non-PR group (dense fibrous: 6.8+/-5.0% vs. 11.6+/-8.4%, p=0.034, calcified: 2.6+/-2.0% vs. 5.1+/-4.4%, p=0.026). In conclusions, PR lesions contain more lipid-rich and less hard plaque components compared with non-PR lesions, which may account for the higher incidence of ACS and plaque vulnerability.

Comparative Study of Nifekalant Versus Amiodarone for Shock-Resistant Ventricular Fibrillation in Out-of-Hospital Cardiopulmonary Arrest Patients

Background: In Japan, intravenous nifekalant (NIF) was often used for direct current cardioversion-resistant ventricular fibrillation (VF), until the use of intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of NIF and AMD has thus far not been compared for resuscitation. Methods and Results: Between August 2007 and April 2009, 403 consecutive out-of-hospital patients with cardiopulmonary arrest were transferred to the Emergency Medical Service of Tokai University. Of these, 30 patients with first defibrillation failure or VF recurrence were enrolled for this NIF/AMD study. The final defibrillation success (and hospital survival rate) was 67% (10/15) in the AMD and 47% (7/15) in the NIF group. The discharge survival rate was 53% (8/15) in the AMD and 21% (4/15) in the NIF group (P = 0.06). Notably, all 4 survivors in the NIF group could take up normal daily life again, whereas this was restricted to only 2 patients from the 11 survivors in the AMD group. The difference is probably partly attributable to longer time from AMD administration to defibrillation success compared with NIF. In the cases of defibrillation failure, VF continued in 4/8 by NIF, however, asystole or pulseless electrical activity occurred in 4/5 patients by AMD. Conclusions: AMD may be borderline superior over NIF to facilitate defibrillation in out-of-hospital patients with cardiopulmonary arrest. However, from the view point of preservation of brain function, NIF is not inferior to AMD for CPR.

Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation

A previous study from our laboratory has shown that a single targeted heavy ion irradiation (THIR; 15 Gy) to rabbit hearts increases connexin43 (Cx43) expression for 2 wk in association with an improvement of conduction, a decrease of the spatial inhomogeneity of repolarization, and a reduction of vulnerability to ventricular arrhythmias after myocardial infarction. This study investigated the time- and dose-dependent effects of THIR (5-15 Gy) on Cx43 expression in normal rabbit hearts (n = 45). Five rabbits without THIR were used as controls. A significant upregulation of Cx43 protein and mRNA in the ventricular myocardium was recognized by immunohistochemistry, Western blotting, and real-time PCR from 2 wk up to 1 yr after a single THIR at 15 Gy. THIR > or =10 Gy caused a significant dose-dependent increase of Cx43 protein and mRNA 2 wk after THIR. Anterior, lateral, and posterior free wall of the left ventricle, interventricular septum, and right ventricular free wall were affected similarly by THIR in terms of Cx43 upregulation. The radiation-induced increase of immunolabeled Cx43 was observed not only at the intercalated disk region but also at the lateral surface of ventricular myocytes. The increase of immunoreactive Cx43 protein was predominant in the membrane fraction insoluble in Triton X-100, that is the Cx43 in the sarcolemma. In vivo examinations of the rabbits 1 yr after THIR (15 Gy) revealed no significant changes in ECGs and echocardiograms (left ventricular dimensions, contractility, and diastolic function), indicating no apparent late radiation injury. A single application of THIR causes upregulation and altered cellular distribution of Cx43 in the ventricles lasting for at least 1 yr. This long-lasting remodeling effect on gap junctions may open the pathway to novel therapy against life threatening ventricular arrhythmias in structural heart disease.

Inducibility of Ventricular Arrhythmia 1 Year Following Treatment with Heavy Ion Irradiation in Dogs with Myocardial Infarction

Targeted external heavy ion irradiation (THIR) of rabbit hearts 2 weeks after myocardial infarction (MI) reduced the vulnerability of fatal ventricular tachyarrhythmias (VT/VF) in association with the increased connexin43 (Cx43). Increased Cx43 was maintained for at least 1 year in normal rabbits, but the long‐term antiarrhythmic effects in the MI model are unknown. We investigated the propensity for late potentials and VT/VF inducibility.

Normal 123 I-MIBG uptake areas may be associated with hyperinnervation and arrhythmia risk in phenol model rabbit hearts: AMINO et al .

Iodine‐123 metaiodobenzylguanidine (123I‐MIBG) is useful for detecting sympathetic innervation in the heart, and has been closely associated with fatal arrhythmias. However, such imaging is typically calibrated to the area of highest uptake and thus is unable to identify areas of hyperinnervation. We hypothesized that normal 123I‐MIBG uptake regions in the denervated heart would demonstrate nerve sprouting and correlate with the potential for arrhythmogenesis.

Effective Pacing Therapy for Syncope with Severe Orthostatic Hypotension and Chronotropic Incompetence

Orthostatic hypotension (OH) occurs during body posture changes from supine to standing within few minutes. There have been several reports that pacemaker therapy improved the symptoms of drug refractory OH. An 83 year old male patient presented to us with recurrent syncopal episodes. The patient was having drug-refractory OH and sinus bradycardia with chronotropic incompetence. TheProtos DR/CLS (Biotronik, Germany) cardiac pacemaker was implanted. This pacemaker has a rate response function of closed loop stimulation (CLS). The CLS function continuously monitors cardiac contraction dynamics through intracardiac local electrical impedance measurement via a ventricular pacing lead, and translates the cardiac contraction dynamics into its pacing rates. We evaluated the effectiveness of the DDD-CLS pacing for the change of his blood pressure (BP) and heart rate (HR) during tilt test comparing to DDD mode. In the DDD mode, after tilt test, the patient’s HR was hold in 46 bpm, and systolic BP was dropped from 110 mmHg to 67 mmHg. The patient developed symptoms of pre-syncope during postural changes. In the DDD-CLS mode, a systolic BP dropped from 129 mmHg to 91 mmHg after tilting, but at almost same time, pacing HR was increased 18 ppm, from 61 ppm to 79 ppm, and the systolic BP was increased to 103 mmHg in 3 minutes. Thereafter, pacing rate was gradually decreased to 65 ppm and systolic BP was maintained at around 95 mmHg. Syncopal recurrence was not exhibited during postural changes setting to the DDD-CLS mode. The rate response function of CLS mode could be suppressed OH patient’s syncopal episode with chronotropic incompetence and improve quality of life of the patient suffering from OH.