Akira Hamabe

Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease.

Previous studies showed a weak correlation between endothelial function of the coronary arteries as assessed by acetylcholine and brachial artery vasomotion during reactive hyperemia. When the same stimulus was used, we obtained a strong correlation between flow-mediated dilation in the coronary and brachial arteries (r=0.78, p <0.001), so that noninvasive assessment of flow-mediated dilation in the brachial artery could be used as a surrogate measure for coronary artery endothelial function.

Altered Atrial Electrical Restitution and Heterogeneous Sympathetic Hyperinnervation in Hearts With Chronic Left Ventricular Myocardial Infarction Implications for Atrial Fibrillation

Background The substrates for the increased incidence of atrial fibrillation (AF) in hearts with chronic left ventricular myocardial infarction (MI) remain poorly defined. We hypothesized that chronic MI is associated with atrial electrical and neural remodeling that enhances AF vulnerability. Methods and Results We created MI in 8 dogs by permanent occlusion of the left anterior descending (LAD) coronary artery. Seven dogs (3 with thoracotomy) that had no LAD occlusion served as controls. Eight weeks after surgery, the incidence and duration of pacing‐induced AF in the open chest anesthetized state were significantly (P<0.05) higher in the MI than in control dogs. Multisite biatrial monophasic action potential (MAP) recordings showed increased heterogeneity of MAP duration (MAPD) and MAPD restitution slope. AF in the MI groups was preceded by significantly higher MAPD (P<0.01) and MAP amplitude (P<0.05) alternans in both atria compared with controls. Epicardial mapping using 1792 bipolar electrodes (1‐mm spatial resolution) showed multisite wavebreaks of the paced wavefronts leading to AF in MI but not in control dogs. Multiple wavelets in MI dogs were associated with significantly higher incidence and longer duration of AF compared with control. The density of biatrial tyrosine hydroxylase (TH) and growth‐associated protein43 (GAP43) nerves were 5‐ to 8‐fold higher and were more heterogeneous in MI compared with control dogs. Conclusions Chronic ventricular MI with no atrial involvement causes heterogeneous alteration of atrial electrical restitution and atrial sympathetic hyperinnervation that might provide important substrates for the observed increased AF vulnerability. (Circulation. 2003;108:360‐366.)

Impaired Endothelium-Dependent Vasodilation in the Brachial Artery in Variant Angina Pectoris and the Effect of Intravenous Administration of Vitamin C

UNLABELLED Endothelial dysfunction in the coronary artery contributes to the pathogenesis of variant angina, and endothelial dysfunction in variant angina may be associated with increased oxidant stress in the systemic arteries. We investigated whether endothelial dysfunction exists in the peripheral artery in patients with variant angina, and also examined the effect of vitamin C, an antioxidant, on endothelium-dependent vasodilation. Using high-resolution ultrasound, both the flow-mediated vasodilation (FMD, endothelium-dependent vasodilation) and sublingual nitroglycerin-induced vasodilation (NTG-D, endothelium-independent vasodilation) in the brachial artery were measured in 28 patients with variant angina and 24 control subjects who had normal coronary arteries. FMD was significantly impaired in patients with variant angina compared with control subjects (1.8 +/- 2.2% vs 6.4 +/- 4.9%, p <0.001). FMD and NTG-D before and after intravenous administration of either vitamin C or placebo were measured in 17 patients with variant angina. FMD significantly improved after the administration of vitamin C (from 2.2 +/- 2.4% to 4.5 +/- 1.6%, p <0.01), but not after administration of the placebo (from 2.0 +/- 2.6% to 1.7 +/- 1.9%). The improved FMD due to vitamin C in patients with variant angina, however, was not significantly different from that in the control subjects. NTG-D was not significantly different between patients with variant angina and control subjects (14.0 +/- 7.8% vs 13.6 +/- 5.0%) and it was also not affected by vitamin C. IN CONCLUSION (1) FMD in the brachial artery is impaired in patients with variant angina, and (2) the acute administration of the antioxidant, vitamin C, was observed to reverse this endothelial dysfunction. These findings support the theory that the systemic inactivation of nitric oxide due to oxidative stress might exist in patients with variant angina.

Effect of Chronic Oral Supplementation with Vitamins on the Endothelial Function in Chronic Smokers

Cigarette smoking has been associated with endothelial dysfunction including impaired endothelium-dependent flow-mediated dilation (FMD). In cigarette smokers, increased oxygen-derived free radicals have been suspected of being one of the major causes of endothelial dysfunction, owing possibly to the inactivation of nitric oxide by free radicals. Vitamins C and E are widely used antioxidant vitamins, which have also been reported to effectively improve the endothelial function in several conditions. To test the effect of moderate-term oral antioxidant vitamin supplementation on the endothelial function in smokers, the authors evaluated the combined effect of vitamins C and E, administered in normal dosages, on FMD in young male smokers. A prospective interventional study was performed. In 15 healthy male subjects (mean age, 24.4 ±2.5 years old). They studied FMD in the brachial artery by using high-resolution ultrasound. The vascular effects of moderate-term oral supplementation with vitamin C (1.0 g/day) and vitamin E (500 mg/day) were determined during reactive hyperemia, which causes endothelium-dependent FMD. They performed a vascular function study 3 times including before vitamin supplement, after 25 days of vitamin supplement, and 4 weeks after the cessation of the vitamin supplement. The flow-mediated dilator response measurements were repeated twice a day before vitamin supplements, and the repeatability obtained from these measurements was found acceptable (variability of FMD <2%). The oral antioxidant vitamin supplement significantly restored FMD (3.8 ±2.2% vs 5.9 ±2.5%; p<0.05), however, this effect disappeared 4 weeks after the vitamin supplementations ended. The combined usual dosage of vitamins C and E supplements was found to improve the endothelial function in chronic smokers.

Recombinant interferon alpha treatment decreases heart rate variability indices and impairs exercise tolerance in patients with chronic hepatitis.

Complications of interferon (IFN) therapy include cardiac arrhythmias, impaired cardiac function and myocardial ischemia. Decreased heart rate variability (HRV) indices, impaired exercise tolerance and decreased left ventricular (LV) function are related to unfavorable outcome of heart disease. To investigate the effect of IFN therapy on HRV, exercise tolerance and cardiac function, 24-h ambulatory electrocardiographic monitoring (AECG), two-dimensional echocardiography, and exercise treadmill testing (ETT) was performed in 9 patients (age 56 +/- 9 years-old) with chronic hepatitis and without underlying heart disease before and after treatment with IFN (recombinant alpha 2b; 10 x 10(6) U/day for 4 weeks). HRV parameters consisted of standard deviation of RR interval (sdNN, ms), SDANN (ms), S.D. index (ms), rMSSD (ms), pNN50 (%) and frequency analysis of heart rate spectrum resulted in low (ms, 0.04-0.15 Hz), high (ms, 0.15-0.40 Hz) and total (ms, 0.01-1.00 Hz) frequency components. Ischemia was not detected by AECG or ETT, and LV function was normal after INF treatment in all patients. However, INF treatment resulted in a decrease in exercise tolerance time (449 +/- 94 s vs. 329 +/- 67 s, P < 0.05) and a decrease in several HRV parameters (S.D. index, 42 +/- 5 ms vs. 37 +/- 9 ms; rMSSD, 22 +/- 5 ms vs. 19 +/- 4 ms; pNN50, 4 +/- 3% vs. 2 +/- 1%; P < 0.05). Further, patients treated with INF tended to have a lower sdNN and total frequency spectra, although this difference did not reach the level of statistical significance. These data suggest that the arrhythmogenic effect of INF may be mediated by decreases in HRV and impairment of exercise tolerance even in patients without overt heart diseases. Further, INF therapy may be contraindicated in patients with predisposing severe cardiac disorders, including arrhythmias, ischemia and decreased LV function.

Primary Mural Endocarditis Without Valvular Involvement

Primary mural endocarditis is an extremely rare infection in which nonvalvular endocardial involvement is seen without any cardiac structural abnormalities such as ventricular septal defects. The rapid and precise diagnosis of this disease remains challenging. We present 2 cases (67‐ and 47‐year‐old male patients) of pathologically confirmed primary mural endocarditis that could have been detected by initial transthoracic echocardiography in the emergency department. Transthoracic echocardiography and transesophageal echocardiography play critical roles in the early recognition and confirmation of primary mural endocarditis.

Successful diagnosis of an atypical prosthetic vascular graft infection without perivascular abscess: luminal vegetation as the hidden septic source.

A 62-year-old woman with a vascular prosthesis for a common hepatic artery aneurysm (3 years ago) was hospitalized because of a 2-week history of lumbago and fever. Six months previously, she was hospitalized at another medical facility for 1 month because of a fever of unknown pathogenesis. Laboratory examination revealed moderate inflammation with an elevated C-reactive protein level of 6.5 mg/dL and a white blood cell count of 7070/mm3. Initial 8-row multi-detector computed tomography (CT) with contrast agent in the emergency department did not show any focus for the origin of the fever. She was referred to the orthopedic surgery department, and MRI of the pelvis revealed inflammation of the left sacroiliac joint (Figure 1). Her first 2 sets of blood cultures were positive for Streptococcus anginosus . Intravenous administration of ampicillin/cloxacillin sodium was started. She was then transferred to the cardiology department for the evaluation of septicemia, which could have been caused by infectious endocarditis. A transthoracic echocardiogram showed severe aortic regurgitation, which was not seen at the time of previous surgery for the vascular prosthesis (Figure 2A). However, a transesophageal echocardiogram only detected a small degenerative change in the right coronary cusp of the aortic valve, which could be healed …

Effect of antiarrhythmic agents on heart rate variability indices after myocardial infarction: comparative experimental study of aprindine and procainamide

The cardiac arrhythmic suppression trial (CAST) reported that antiarrhythmic treatments in post-myocardial infarction (MI) patients resulted in poor outcome and decreased in heart rate variability indices (HRV). The goal of the present study was to determine whether aprindine and procainamide, antiarrhythmic agents that increase HRV, result in beneficial effects in post-MI rabbits. Four weeks before experiment, MI was induced in four rabbits by ligating the major branch of left coronary artery. A total of eight rabbits (four post-MI and four normal rabbits) were randomly assigned to treatment with either intravenous aprindine (1 mg/kg) or intravenous procainamide (15 mg/kg). Frequency domain HRV (low frequency spectra, LF, 0.04-0.15 Hz; high frequency spectra, HF, 0.15-0.40 Hz) were assessed by MemCalc software. Aprindine significantly increased HF and LF in both MI and normal rabbits, whereas procainamide tended to decrease HF and LF in MI and normal rabbits (in total rabbits; aprindine, LF, from 6.3 +/- 7.9 to 16.5 +/- 15.0 ms(2)/Hz, P < 0.05; HF, from 8.0 +/- 11.7 to 17.5 +/- 15.0 ms(2)/Hz, P < 0.05; procainamide, LF, from 4.9 +/- 7.4 to 4.8 +/- 8.5 ms(2)/Hz, NS; HF, from 11.1 +/- 23.0 to 5.1 +/- 10.6 ms(2)/Hz, NS). Under pharmacological denervation with propranolol (0.1 mg/kg) and atropine (0.04 mg/kg), aprindine increased LF and HF (LF, from 0.2 +/- 0.2 to 0.8 +/- 0.7 ms(2)/Hz, P < 0.05; HF, from 0.1 +/- 0.0 to 0.2 +/- 0.0 ms(2)/Hz, P < 0.05). These data suggest that aprindine can increase HRV in post-MI rabbits. Further experiments in human subjects would be of benefit.

‘Honeycomb appearance’ on three-dimensional transthoracic echocardiography as the landmark of left ventricular non-compaction: two case reports

IntroductionLeft ventricular non-compaction is a rare congenital heart disease, and is most commonly diagnosed via two-dimensional echocardiography according to echocardiographic criteria. Recently, transthoracic three-dimensional echocardiography has become available in the clinical setting.Case presentationWe present two isolated cases of left ventricular non-compaction from Japan (in an 84-year-old woman and 47-year-old man) that were confirmed by two-dimensional echocardiography, contrast-enhanced two-dimensional echocardiography, three-dimensional echocardiography and cardiac magnetic resonance imaging. In both cases, three-dimensional echocardiography successfully demonstrated the trabecular meshwork of the left ventricle, referred to as a ‘honeycomb appearance’.ConclusionsThree-dimensional echocardiography has the advantage of visualizing an en-face view of the trabecular meshwork, which is not possible with two-dimensional echocardiography. We further emphasize the clinical utility of three-dimensional echocardiography, which is not limited to just the observation of the trabeculations and inter-trabecular recesses, but can also visualize the trabecular meshwork with a ‘honeycomb appearance’.

Newly developed mobile mass superimposed on mitral annulus calcification in patient with cerebral infarction: Documentation of a unique embolic source

Mitral annulus calcification (MAC) has been recognized as a potent risk factor to cause cerebral infarction. There has been suggested possible linkage between mass on MAC and systemic embolic events. We report a case of cerebral infarction with newly developed mobile mass superimposed on MAC.