Biomedical subjects

Shunichi Homma

Publications and source records attributed to Shunichi Homma.

69 records · Page 4Linked to original sources

PubMed2003

Patent Foramen Ovale and Stroke.

Observational data from prospective and retrospective trials indicate that a patent foramen ovale (PFO) is associated with the risk of ischemic stroke. The mechanism involved is presumed to be paradoxical embolism from a venous thrombus that travels via the PFO to the systemic circulation causing an ischemic stroke. Primary stroke prevention data for patients with a PFO are nonexistent. Given the substantial prevalence of PFO in the total population (~ 25% to 30%), a primary prevention study may not be feasible. However, whether targeted primary prevention for patients with PFOs of certain morphologic characteristics (eg, larger size, greater degree of shunt) would be possible remains undefined. Given the large number of asymptomatic subjects, no therapy is currently recommended. The best treatment modality to prevent recurrent stroke in patients with PFO has not been defined. There are four major treatment choices: surgical closure, percutaneous device closure, medical therapy with anticoagulants, and medical therapy with antiplatelet agents. Regarding medical therapy, the Patent Foramen Ovale in Cryptogenic Stroke Study has demonstrated that antiplatelet and anticoagulant therapies are of equal benefit in preventing recurrent adverse events. Although closure of the PFO, either surgical or percutaneous, may further reduce the event rates, this remains to be demonstrated because no randomized trial to date has compared PFO closure with medical therapy.

Journal Article↗

PubMed2003

Automated quantification of left ventricular function by the automated contour tracking method.

The automated contour tracking (ACT) method has been developed for the automated measurement of area volume using the energy minimization method without tracing a region of interest. The purpose of this study was to compare the ACT method and left ventriculography (LVG) for the measurement of left ventricular (LV) function in the clinical setting. An apical four-chamber view was visualized by two-dimensional echocardiography and recorded for off-line analysis in 14 patients with high-quality images who underwent LVG. The ACT method automatically traces the endocardial border from the recorded images and calculates LV volumes (end-diastole and end-systole) and ejection fraction (EF). Both ACT and LVG were compared by linear regression analysis for the measurement of EF. EF determined by the ACT method agreed well with that by LVG (r = 0.96, y = 0.94x + 4.6, standard error of the estimate = 3.9%). The mean difference between the ACT and LVG was -1.4%+/- 7.3%. In conclusion, the ACT method is reliable for noninvasive estimation of EF in high-quality images. This suggests that this new technique may be useful in the automated quantification of LV function.

Adult↗

PubMed2003

Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy.

Lipoprotein lipase is the principal enzyme that hydrolyzes circulating triglycerides and liberates free fatty acids that can be used as energy by cardiac muscle. Although lipoprotein lipase is expressed by and is found on the surface of cardiomyocytes, its transfer to the luminal surface of endothelial cells is thought to be required for lipoprotein lipase actions. To study whether nontransferable lipoprotein lipase has physiological actions, we placed an alpha-myosin heavy-chain promoter upstream of a human lipoprotein lipase minigene construct with a glycosylphosphatidylinositol anchoring sequence on the carboxyl terminal region. Hearts of transgenic mice expressed the altered lipoprotein lipase, and the protein localized to the surface of cardiomyocytes. Hearts, but not postheparin plasma, of these mice contained human lipoprotein lipase activity. More lipid accumulated in hearts expressing the transgene; the myocytes were enlarged and exhibited abnormal architecture. Hearts of transgenic mice were dilated, and left ventricular systolic function was impaired. Thus, lipoprotein lipase expressed on the surface of cardiomyocytes can increase lipid uptake and produce cardiomyopathy.

Animals↗

PubMed2003

The effect of maternal cocaine exposure on neonatal rat cardiac function.

Fetal cocaine exposure has been associated with a variety of cardiovascular dysfunctions in humans. We treated pregnant rats with either saline or cocaine at 60 mg/kg by gastric lavage for the entire gestational period and for 14 days after parturition. We then performed high-frequency transthoracic echocardiography to determine whether cocaine exposure affected neonatal cardiac contractile function in vivo in 7- and 14-day-old neonatal rats. All studies were performed in the unsedated, conscious state. Heart rate (HR) and systolic function, expressed as fractional area of change at the midpapillary muscle level, were calculated from two-dimensional images. Resting HR was faster in the cocaine-exposed group at both ages, but baseline contractile function was not different between control (CTL) and cocaine-exposed (COC) neonatal rats. Dobutamine induced a significant increase in HR in all groups at only the largest dose tested (Day 7 CTL HR increased from 438 +/- 3 bpm to 462 +/- 10 bpm; Day 7 COC HR increased from 466 +/- 3 bpm to 493 +/- 7 bpm; Day 14 CTL HR increased from 443 +/- 4 bpm to 487 +/- 4 bpm; Day 14 COC HR increased from 477 +/- 4 bpm to 501 +/- 5 bpm). Dobutamine elicited a significant increase in contractile response at both Day 7 (from 76.6% +/- 0.6% to 81.5% +/- 0.7%) and Day 14 in CTL (from 78.2% +/- 0.7% to 81.9% +/- 0.7%), but not in COC, animals (from 76.7% +/- 0.8% to 78.9% +/- 0.8% at Day 7 and from 76.8% +/- 1.1% to 79.3% +/- 0.8% at Day 14). Epinephrine induced a significant increase in contractile response in CTL, but not in COC, rats at Day 7 and had no effect on fractional area of change at 14 days of age in either CTL or COC animals. Our results indicate that perinatal cocaine exposure does not modify resting contractile function but attenuates the contractile response to beta-adrenoceptor stimulation in the neonatal rat. These results suggest that perinatal cocaine exposure may lead to decreased responsiveness to inotropic drugs during the early neonatal period.

Adrenergic alpha-Agonists↗

PubMed2003

Hypercoagulable States in patients with patent foramen ovale.

A patent foramen ovale (PFO) is a risk factor for stroke with the presumed mechanism being paradoxical embolism. Hypercoagulable states have been associated with the propensity to develop venous thromboses and have been separately associated with the risk for ischemic stroke. A PFO could provide the missing link. Having a PFO and a hypercoagulable state may place a person at an increased risk for paradoxical embolism. However, the prevalence of PFO in patients with hypercoagulable states and vice versa is unknown, and the best therapeutic strategy for these patients is unelucidated. This review assesses the literature, provides some insight on these topics, and identifies areas for further investigation.

Blood Coagulation Disorders↗

PubMed2002

Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study.

BACKGROUND: Patent foramen ovale (PFO) is associated with stroke, but there are no randomized studies to evaluate the efficacy of antithrombotic therapies. METHODS AND RESULTS: The PFO in Cryptogenic Stroke Study was a 42-center study that evaluated transesophageal echocardiographic findings in patients randomly assigned to warfarin or aspirin in the Warfarin-Aspirin Recurrent Stroke Study. In this study, 630 stroke patients were enrolled, of whom 312 (49.5%) were randomized to warfarin and 318 (50.5%) to aspirin. Of these, 265 patients experienced cryptogenic stroke and 365 experienced known stroke subtypes. End points were recurrent ischemic stroke or death. PFO was present in 203 patients (33.8%). There was no significant difference in the time to primary end points between those with and those without PFO in the overall population (P=0.84; hazard ratio 0.96; 95% CI 0.62 to 1.48; 2-year event rates 14.8% versus 15.4%) or in the cryptogenic subset (P=0.65; hazard ratio 1.17; 95% CI 0.60 to 2.37; 2-year event rates 14.3% versus 12.7%). There was no significant difference among those with no, small, or large PFO (P=0.41 for small PFO and P=0.16 for large PFO; 2-year event rates for no, small, and large PFO, 15.4%, 18.5%, and 9.5%, respectively). There was no significant difference between patients with isolated PFO and those with PFO in association with atrial septal aneurysm (P=0.84; 2-year event rates 14.5% versus 15.9%). In patients with PFO, there was no significant difference in the time to primary end points between those treated with warfarin and those treated with aspirin (P=0.49; hazard ratio 1.29; 95% CI 0.63 to 2.64; 2-year event rates 16.5% versus 13.2%). CONCLUSIONS: On medical therapy, the presence of PFO in stroke patients did not increase the chance of adverse events regardless of PFO size or the presence of atrial septal aneurysm.

Adult↗

PubMed2002

Physical activity attenuates the effect of increased left ventricular mass on the risk of ischemic stroke: The Northern Manhattan Stroke Study.

OBJECTIVES: The goal of this study was to determine whether the risk of ischemic stroke associated with increased left ventricular mass (LVM) is modified by physical activity (PA). BACKGROUND: Increased LVM is associated with an increased risk for stroke. Physical activity can decrease the risk of stroke and may have variable effects on LVM. METHODS: We used a case-control study design in a multiethnic population in northern Manhattan, New York, to study 394 case subjects who had a first ischemic stroke and 413 stroke-free control subjects. All subjects were interviewed and two-dimensional echocardiograms obtained to determine LVM. RESULTS: A sharp increase in risk of ischemic stroke was seen in the highest quartile of LVM (odds ratio [OR]: 6.14 [95% confidence interval [CI]: 3.04 to 12.38]). Thus, increased LVM was defined by the highest quartile of LVM. In multivariate analysis, the effect of increased LVM on the risk of stroke was significantly decreased by the presence of any level of PA versus no PA (OR: 1.59 [95% CI: 0.99 to 2.57] p < 0.07 vs. 3.53 [95% CI: 1.94 to 6.42] p < 0.0001). Although PA decreased the risk of stroke in all patients, the effect was stronger in subjects with increased LVM than among those without increased LVM (p = 0.033). CONCLUSIONS: Increased LVM is associated with an increased risk of stroke, especially among sedentary patients. Physical activity decreases the risk of stroke among patients with increased LVM to a level comparable to that of patients without increased LVM. Recommending PA may be a nonpharmacologic tool to reduce the stroke risk, especially among patients with increased LVM.

Aged↗

PubMed2002

Suppression of murine cardiac allograft arteriopathy by long-term blockade of CD40-CD154 interactions.

BACKGROUND: The interaction between CD40 on antigen-presenting cells and CD40L on T cells is critical in allograft rejection. CD154 blockade suppresses allograft rejection, but the role of this pathway in allograft vasculopathy remains obscure. METHODS AND RESULTS: A vascularized murine heterotopic cardiac transplant model was used to test whether perioperative CD154 blockade suppresses allograft vasculopathy or whether long-term CD154 blockade is required to suppress allograft vasculopathy. Perioperative CD154 blockade consisted of MR1 given on days -1, 1, and 3; long-term blockade consisted of MR1 given on days -1, 1, and 3 and continued twice weekly for 8 weeks. Allografts treated with perioperative or long-term CD154 blockade survived indefinitely. Perioperative and long-term treatment with control antibody (Ha4/8) resulted in uniform early rejection. Perioperative CD154 blockade transiently reduced early T-cell and macrophage infiltration in parallel with a transient reduction in endothelial adhesion receptor expression. Although perioperative CD154 blockade prevented allograft failure, it did not reduce allograft vasculopathy; mean neointimal cross-sectional area in perioperative MR1-treated and Ha4/8-treated recipients was 43+/-7% and 50+/-12%, respectively (P=NS). In contrast, mean neointimal cross-sectional area in long-term, MR1-treated recipients was 19+/-3% (P<0.001 versus perioperative MR1). Long-term CD154 blockade also suppressed endothelial E-selectin, P-selectin, and intracellular adhesion molecule-1 expression and improved graft function 3.5-fold versus control (P<0.05). CONCLUSIONS: These data show that perioperative CD154 blockade mitigates acute rejection but long-term CD154 blockade may result in decreased allograft endothelial activation and is required to suppress allograft arteriopathy.

Animals↗

PubMed2002

Change in coronary flow reserve on transthoracic Doppler echocardiography after a single high-fat meal in young healthy men.

BACKGROUND: High-fat meals and elevated triglyceride levels are associated with cardiovascular disease. In recent studies of brachial artery vasoactivity, a single high-fat meal reduced endothelial function in young healthy men. It is unknown whether coronary microcirculation is affected after high-fat meals. OBJECTIVE: To evaluate change in coronary flow reserve after a single high-fat meal. DESIGN: Controlled interventional study. SETTING: University hospitals. PATIENTS: 15 young healthy men (mean age [+/-SD], 29 +/- 4 years). INTERVENTION: Coronary flow reserve was determined by using transthoracic Doppler echocardiography before and after consumption of a high-fat meal in all 15 men and before and after consumption of a low-fat meal in 5 of 15 men. MEASUREMENTS: Coronary flow reserve, lipid levels, and hemodynamic characteristics. RESULTS: In all men, triglyceride levels increased significantly from baseline 5 hours after the high-fat meal, from 1.1 mmol/L to 2.8 mmol/L (100 mg/dL to 250 mg/dL) (P < 0.001). Average coronary flow reserve was 4.02 before and 3.30 5 hours after the high-fat meal (decrease, 18% [95% CI, 13% to 23%]). In the 5 men who received both meals, mean coronary flow reserve decreased by 0.79 after the high-fat meal and increased by 0.07 after the low-fat meal (difference, -0.86 [CI, -1.36 to -0.37]; P = 0.03). Mean triglyceride levels increased by 1.6 mmol/L (140 mg/dL) after the high-fat meal and 0.1 mmol/L (10 mg/dL) after the low-fat meal (difference, 1.5 mmol/L [CI, 0.3 to 2.7 mmol/L], 130 mg/dL [CI, 23 to 236 mg/dL]; P = 0.03). CONCLUSIONS: Coronary flow reserve decreased after a single high-fat meal in young healthy men. High-fat meals may be detrimental to coronary microcirculation.

Adult↗

PubMed2002

Mechanisms of cardioembolic stroke.

Cardiac embolism is often involved as a mechanism for embolic stroke, and may be implicated in many strokes that have traditionally been considered of unknown origin (cryptogenic strokes). In recent years, significant advancements have been made in understanding and reducing the risk of stroke from long-known cardioembolic sources (atrial fibrillation, intracardiac thrombus or tumor, infective endocarditis). Also, improved cardiac imaging, especially transesophageal echocardiography, has allowed the identification of newer embolic sources of stroke (aortic atheromas, patent foramen ovale, atrial septal aneurysm). This article reviews the current understanding of cardiac embolism as a mechanism for stroke, and the preventive options that are currently adopted to decrease the stroke risk.

Anticoagulants↗

PubMed2002

Transesophageal echocardiography aortic plaque imaging.

Despite some limitations, TEE is a sensitive and specific diagnostic technique for the diagnosis and evaluation of aortic plaque. TEE provides a semi-invasive, portable, and widely available means for assessing aortic plaque and associated embolic risk in patients with embolic events, thus guiding rational therapeutic choices. Improvement in tissue characterization and three-dimensional capabilities may further improve the diagnostic accuracy of TEE for aortic plaque detection and evaluation.

Aorta↗

PubMed2002

Giant aneurysm of the membranous ventricular septum extending outside the heart: diagnosis by transthoracic color flow Doppler echocardiography.

Aneurysm of the membranous ventricular septum (AMS) is a congenital cardiac anomaly often associated with ventricular septal defect. This aneurysm usually pouches into the right side of the heart and remains intracardiac. An AMS that extends outside of the heart is rare. We report an unusual case of a giant extracardiac AMS diagnosed by transthoracic color flow Doppler echocardiography.

Cardiac Catheterization↗

PubMed2002

Exercise training normalizes altered calcium-handling proteins during development of heart failure.

The cardiac sarcoplasmic reticulum calcium-ATPase (SERCA2a), Na+/Ca2+ exchanger (NCX1), and ryanodine receptor (RyR2) are proteins involved in the regulation of myocyte calcium. We tested whether exercise training (ET) alters those proteins during development of chronic heart failure (CHF). Ten dogs were chronically instrumented to permit hemodynamic measurements. Five dogs underwent 4 wk of cardiac pacing (210 beats/min for 3 wk and 240 beats/min for the 4th wk), whereas five dogs underwent the same pacing regimen plus daily ET (5.1 +/- 0.3 km/h, 2 h/day). Paced animals developed CHF characterized by hemodynamic abnormalities and reduced ejection fraction. ET preserved resting hemodynamics and ejection fraction. Left ventricular samples were obtained from all dogs and another five normal dogs for mRNA (Northern analysis, band intensities normalized to glyceraldehyde-3-phosphate dehydrogenase) and protein level (Western analysis, band intensities normalized to tubulin) measurements. In failing hearts, SERCA2a was decreased by 33% (P < 0.05) and 65% (P < 0.05) in mRNA and protein level, respectively, compared with normal hearts; there was only an 8.6% reduction in mRNA and a 32% reduction in protein in exercised animals (P < 0.05 from CHF). mRNA expression of NCX1 increased by 44% in paced-only dogs compared with normal (P < 0.05) but only by 22% in trained dogs (P < 0.05 vs. CHF); protein level of NCX1 was elevated in paced-only dogs (71%, P < 0.05) but partially normalized by ET (33%, P < 0.05 from CHF). RyR2 was not altered in any of the dogs. In conclusion, long-term ET may ameliorate cardiac deterioration during development of CHF, in part via normalization of myocardial calcium-handling proteins.

Animals↗

PubMed2002

Impact of aortic stiffness on ischemic stroke in elderly patients.

BACKGROUND AND PURPOSE: Large atherosclerotic plaques in the aortic arch detected by transesophageal echocardiography (TEE) are associated with increased risk of ischemic stroke in the elderly. The atherosclerotic process also affects aortic distensibility, which can also be assessed by TEE. The purpose of this study was to evaluate the possible association of aortic stiffness by TEE with ischemic stroke in elderly patients. METHODS: We performed TEE in 40 consecutive elderly patients aged > or =55 years with acute ischemic stroke and in 42 consecutive control subjects aged > or =55 years. Aortic stiffness index beta, which has been used in the literature to express the stiffness of the aortic wall, was calculated as follows: beta=ln (systolic blood pressure/diastolic blood pressure)/([D(max)-D(min)]/D(min)), where ln is natural logarithm, D(max) is maximum aortic lumen diameter, and D(min) is minimum aortic lumen diameter by TEE. The association of index beta with ischemic stroke was evaluated by logistic regression analysis after adjustment for potential confounders, including thickness of aortic arch plaques. RESULTS: Index beta was significantly greater in stroke patients than in controls (9.7+/-5.0 versus 5.3+/-3.5; P<0.0001). When aortic plaque thickness and other stroke risk factors were entered in multivariate analysis, index beta was found to be independently associated with ischemic stroke (odds ratio, 1.28 per unit increase; 95% CI, 1.10 to 1.52). CONCLUSIONS: Aortic stiffness by TEE is associated with ischemic stroke, independent of thickness of aortic arch plaques and other stroke risk factors. This suggests that aortic stiffness by TEE may add prognostic information when assessing the risk of ischemic stroke in the elderly.

Acute Disease↗

PubMed2002

Leukocyte count is associated with aortic arch plaque thickness.

BACKGROUND AND PURPOSE: Leukocyte count has been associated with cardiovascular and cerebrovascular disease, including carotid plaque thickness, in several studies. We hypothesized that white blood cell count is associated with aortic arch plaque thickness (AAPT). METHODS: Leukocyte count was measured in randomly selected stroke-free community participants undergoing transesophageal echocardiography. AAPT was measured for each subject and dichotomized into <4 and > or =4 mm (thick plaque). Multivariate linear and logistic regression was used to calculate the effect of leukocyte count on AAPT after adjustment for potential confounding factors. Mean age of the 145 participants was 68.5+/-8.3 years; 43.5% were women; 15.9% were white; 31.7% were black; and 49.0% were Hispanic. RESULTS: Mean leukocyte count was 5.88+/-1.76x10(9)/L. Each unit increase in leukocyte count was associated with a mean 0.28-mm increase in AAPT (P=0.0036). After adjustment for other atherosclerosis risk factors, including age, sex, hypertension, diabetes, hyperlipidemia, and smoking, the relationship persisted (mean increase in AAPT, 0.24 mm; P=0.0064). Thirty-five participants (24.1%) had AAPT > or =4 mm. Mean leukocyte count among those with thick plaque was significantly higher than among those with plaque <4 mm (6.54+/-1.60 versus 5.65+/-1.76x10(9)/L, respectively; P=0.009). Each unit increase in leukocyte count was associated with an increased risk of thick plaque (adjusted odds ratio, 1.38; 95% CI, 1.05 to 1.79). The relationships were similar for men and women and for those <70 or > or =70 years of age. CONCLUSIONS: Leukocyte count is associated with AAPT and is specifically correlated with AAPT > or =4 mm, a degree of thickening associated with increased stroke risk. These findings are consistent with current hypotheses regarding the inflammatory or infectious etiology of risk of atherosclerosis and stroke.

Age Distribution↗