Wen-Lieng Lee

Changes of autonomic tone before the onset of paroxysmal atrial fibrillation

The relationship between autonomic nerve system and the onset of paroxysmal atrial fibrillation (PAF) is still controversial. Furthermore, no prior studies have compared heart rate variability (HRV) between PAF patients with (organic) or without (idiopathic) underlying cardiac diseases. The purpose of this study was to assess the alteration of autonomic tone by analyzing HRV immediately before the onset of atrial fibrillation. This study included 57 patients (M/F: 34/23, 66+/-22 years) with frequent attacks of PAF. All cases underwent 24-h ambulatory Holter monitoring; each patient had one or more episodes of sustained PAF (>30 s). A period of sinus rhythm 40 min was allowed for accurate assessment of HRV over these periods. Spectral HRV was expressed as low (0.04-0.15 Hz) and high (0.15-0.40 Hz) frequency components (LF, HF), and L/H ratio at 2-min intervals over a 40-min period before the onset of PAF. According to HRV, three subtypes were classified; onset of PAF accompanied with increased HF component and decreased L/H ratio was designated as vagal type; decreased HF component and increased L/H ratio was designated as sympathetic type, and the other episodes which did not belong to vagal or sympathetic type were designated as non-related type. In group I (idiopathic PAF, n=30): 63 episodes of PAF were found and vagal type was predominant (41/63, 63.5%); HF increased significantly before the onset of AF. In group II (organic PAF, n=27): 58 episodes of PAF were found and sympathetic type was predominant (39/58, 67.2%); L/H ratio increased before AF onset. None of the three subtypes showed significant circadian distributions in group I and II patients. Changes of HRV before the onset of PAF were not universal; most of the patients with idiopathic PAF were vagal dependent and most of the patients with organic PAF were sympathetic dependent.

INSULIN-LIKE GROWTH FACTOR I IMPROVES CARDIOVASCULAR FUNCTION AND SUPPRESSES APOPTOSIS OF CARDIOMYOCYTES IN DILATED CARDIOMYOPATHY

To investigate how insulin-like growth factor I (IGF-I) modulates cardiovascular function and myocardial apoptosis in heart failure, the therapeutic effects of IGF-I were determined in a canine model of dilated cardiomyopathy. The animals were paced at 220 beats/min, and the left ventricular (LV) chamber became dilated after 2 weeks. A subset of paced dogs was treated with sc injections of IGF-I from week 3 to week 4. After 4 weeks of pacing, untreated paced dogs developed significant ventricular dysfunction. IGF-I-treated paced dogs showed better cardiac output, stroke volume, LV end-systolic pressure, and LV end-diastolic pressure. Moreover, pulmonary wedge pressure and systemic vascular resistance were increased in the untreated group and decreased in the IGF-I-treated group. IGF-I treatment was associated with less thinning of the ventricular wall. Compared with the controls, untreated paced dogs showed increased apoptosis of cardiac muscle cells, which was partially suppressed by IGF-I treatment. The...

Differential Glucose Tolerance in Dipper and Nondipper Essential Hypertension: The implications of circadian blood pressure regulation on glucose tolerance in hypertension

OBJECTIVE The goals of this study were to compare glucose tolerance in dipper and nondipper hypertensive patients and to explore the cause of glucose intolerance in essential hypertension. RESEARCH DESIGN AND METHODS A total of 50 patients <45 years old who had essential hypertension were recruited and studied by 24-h blood pressure monitoring and an oral glucose tolerance test (OGTT). Autonomic function was assessed with spectral analysis of heart rate variability. RESULTS Dipper hypertensive patients (n = 25) had lower nocturnal blood pressure than nondipper (n = 25) patients. During OGTT, postprandial glucose levels were higher in the nondippers at 0,90, and 120 min (all P < 0.05). Nondippers had a higher fasting insulin/glucose ratio than was apparent in normal control subjects. Despite higher postprandial glucose levels, nondippers had lower postprandial insulin levels. These results suggest that nondippers were insulin resistant and that their pancreatic β-cell function was impaired. For all patients, nocturnal reduction of blood pressure was inversely related to total glucose levels under the OGTT curve and was positively related to postprandial insulin levels. Daytime heart rate did not differ between the dippers and nondippers, but nocturnal heart rate was higher in the nondippers, suggesting that nocturnal sympathetic activities were higher among the nondippers. Spectral analysis of heart rate variability suggests that the nondippers had lower parasympathetic activities and unbalanced sympathetic/parasympathetic outflow. CONCLUSIONS These findings indicate that nondipper hypertensive patients are more glucose intolerant than are dipper patients. The abnormalities of glucose metabolism in nondippers could be explained by insulin resistance and β-cell dysfunction. The results of spectral analysis suggest that abnormal autonomic outflow may represent a possible link between hypertension and associated metabolic dysfunction.

Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and neonatal cardiomyocytes

AIMS The objective of this study was to investigate whether a cytoprotective herb-derived agent, Ginkgo biloba extract (EGb) 761, could have a beneficial effect on doxorubicin-induced cardiac toxicity in vitro and in vivo. METHODS AND RESULTS Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 microM), EGb761 (25 microg/mL), or EGb761 plus doxorubicin. After 24 h, doxorubicin upregulated p53 mRNA expression, disturbed Bcl-2 family protein balance, disrupted mitochondrial membrane potential, precipitated mitochondrion-dependent apoptotic signalling, induced apoptotic cell death, and reduced viability of cardiomyocytes, whereas EGb761 pretreatment suppressed all the actions of doxorubicin. Similarly, rats treated with doxorubicin [3 mg/kg intraperitoneally (i.p.) three doses every other day] displayed retarded growth of body and heart as well as elevated apoptotic indexes in heart tissue at both 7 and 28 days after exposure, whereas EGb761 pretreatment (5 mg/kg i.p. 1 day before each dose of doxorubicin) effectively neutralized the aforementioned gross and cellular adverse effects of doxorubicin. CONCLUSION Doxorubicin impairs viability of cardiomyocytes at least partially by activating the p53-mediated, mitochondrion-dependent apoptotic signalling. EGb761 can effectively and extensively counteract this action of doxorubicin, and may potentially protect the heart from the severe toxicity of doxorubicin.

Doxycycline suppresses doxorubicin-induced oxidative stress and cellular apoptosis in mouse hearts

Cardiac toxicity remains a serious yet unsolved complication of doxorubicin. This study was designed to examine whether doxycycline, a tetracycline-derived synthetic antibiotic with potential cytoprotective properties, could ameliorate this complication of doxorubicin. Male mice at 4-week of age were administrated with vehicle, doxorubicin (3mg/kg intraperitoneally every other day at 3 doses), doxycycline (2.5mg/kg intraperitoneally every other day for 3 doses), or doxycycline plus doxorubicin (each dose given 1day post doxycycline). After 28days, left ventricular geometric and systolic parameters were measured by transthoracic echocardiography, and hearts were harvested for extensive analyses regarding oxidative stress and cellular apoptosis. At 28days, hearts of doxorubicin-treated mice were characterized by less weight compared with controls, also with remodeling and depressed systolic function of the left ventricle. Biochemical analyses disclosed that content of malondialdehyde was increased and activity of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, was decreased in these hearts. Both mitochondrion-dependent and endoplasmic reticulum stress-induced apoptotic pathways were also activated in the hearts of doxorubicin-treated mice as reflected by decreased Bcl-2/Bcl-(XL) and elevated Bax/Bad, p53/Apaf-1, endoplasmic reticulum glucose-related protein 78, C/EBP homologous protein, cytochrome c release from mitochondria, caspases-9/-3 cleavage, and cardiomyocyte apoptosis. In contrast, all the above left ventricular remodeling, systolic depressing, oxidative and pro-apoptotic actions of doxorubicin could be significantly alleviated by doxycycline pretreatment. Thus, doxycycline extensively counteracts multiple oxidative and apoptotic actions of doxorubicin in heart, hence may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.

Comprehensive evaluation of ischemic heart disease using MDCT.

OBJECTIVE Recently MDCT has become widely used for the evaluation of ischemic heart disease, but clinically the evaluation is primarily focused on the coronary artery only. We describe why and how to comprehensively evaluate the cardiac CT scan, including myocardium, motion, viability, valve, and perfusion aspects related to ischemic heart disease. CONCLUSION Radiologists should be familiar with the protocol design and comprehensive interpretation of cardiac MDCT to provide comprehensive treatment suggestions for the patients.

Contrast enhancement in cardiac MDCT: comparison of iodixanol 320 versus iohexol 350.

OBJECTIVE The objective of our study was to evaluate whether iodixanol 320 mg I/mL (iodixanol 320), with the highest iodine concentration of dimeric nonionic contrast agents on the market, results in decreased vascular or myocardial enhancement compared with iohexol 350 mg I/mL (iohexol 350). SUBJECTS AND METHODS During a 4-month period, 72 patients referred for cardiac MDCT were consecutively enrolled and randomized into two groups: iohexol 350 and iodixanol 320. The injection and scanning protocols were the same for both groups. Enhancement of the right heart, left heart, coronary arteries, and left ventricular (LV) myocardium in both the arterial and delayed phases was compared using two-tailed independent Students t test. RESULTS Enhancement in the right heart, left heart, coronary arteries, and LV myocardium in the arterial phase showed no statistical difference (p > 0.05) between the two groups, although the iohexol group showed slightly higher enhancement (average, 11.2 H) in all of the areas. Surprisingly, in the delayed phase, the iodixanol group displayed significantly higher (7.7 H) persistent enhancement (p < 0.05) in the LV myocardium. CONCLUSION Iodixanol 320 can provide vascular enhancement in cardiac MDCT that is similar to iohexol 350. In the delayed phase, iodixanol 320 shows significantly higher delayed enhancement (7.7 H) in the LV myocardium than iohexol 350.

Decreased ratio of high-molecular-weight to total adiponectin is associated with angiographic coronary atherosclerosis severity but not restenosis.

BACKGROUND Adiponectin is thought to protect against atherosclerosis and its expression is decreased in metabolic syndrome and diabetes mellitus. Adiponectin has a high-molecular-weight (HMW) multimer structure in the blood. We determined whether circulating HMW adiponectin, total adiponectin, or their ratio predicts baseline angiographic coronary artery disease (CAD) severity and restenosis after percutaneous coronary intervention (PCI). METHODS Patients with stable angina pectoris who underwent PCI for a de novo lesion and had angiographic follow-up at our hospital were retrospectively enrolled. The study patients were grouped as moderate (N=68) or severe (N=63) coronary atherosclerosis by the baseline median Gensini severity score (moderate<22, severe> or =22). RESULTS Univariate analysis showed that subjects in the severe CAD group had a lower HMW/total adiponectin ratio (0.32+/-0.19 vs. 0.37+/-0.16, p=0.024) while the absolute value of HMW adiponectin (2.17+/-2.05 vs. 2.27+/-2.07 microg/ml, p=0.389) and total adiponectin (5.97+/-3.12 vs. 5.76+/-2.91 microg/ml, p=0.807) were similar between the severe and moderate CAD groups. In a multivariate binary logistic regression model, a higher serum HMW/total adiponectin ratio (odds ratio 0.058, p=0.018) was negatively, while hypercholesterolemia (OR 2.475, p=0.029) was positively associated with coronary atherosclerosis disease severity. In terms of restenosis after PCI (mean follow-up at 12+/-13 months), HMW adiponectin, total adiponectin and their ratio were similar between restenotic (N=91) and non-restenotic groups (N=40). CONCLUSIONS A decreased ratio of circulating HMW adiponectin to total adiponectin is associated with angiographic disease severity but not restenosis in CAD patients undergoing PCI.

MRI Measured Epicardial Adipose Tissue Thickness at the Right AV Groove Differentiates Inflammatory Status in Obese Men With Metabolic Syndrome

Epicardial adipose tissue (EAT) is a metabolically active visceral fat, which secretes inflammatory cytokines and adipokines. In this study, our aim was to examine which measurements of EAT thickness by magnetic resonance imaging (MRI) could best help differentiate inflammatory status, classified by levels of high‐sensitivity C‐reactive protein (hs‐CRP), in obese men with metabolic syndrome (MetS). We prospectively enrolled 32 men with central obesity (waist circumference ≥90 cm) and at least two other MetS criteria. MRI examinations for measurements of EAT, subcutaneous fat, and abdominal visceral fat as well as recordings of anthropometric parameters and tests for serum inflammatory cytokines and adipokines were conducted. Subjects with MetS (N = 32) were divided into three subgroups: (i) low inflammatory status (hs‐CRP < 0.3 mg/dl, N = 8), (ii) intermediate inflammatory status (hs‐CRP 0.1–0.3 mg/dl, N = 15), and (iii) high inflammatory status (hs‐CRP >0.3 mg/dl, N = 9). EAT thickness at the right atrioventricular (AV) groove showed a significant linear trend among the three subgroups of MetS (P for trend = 0.004). High inflammatory status MetS subgroup had a significantly thicker right AV groove EAT than did the low inflammatory status MetS subgroup (19.3 ± 3.1 vs. 14.4 ± 3.3 mm, P = 0.015). In binary logistic regression analysis, right AV groove EAT thickness was an independent predictor for differentiating inflammatory status in MetS while abdominal visceral fat area and insulin‐resistance index were not. In conclusion, MRI measured EAT thickness at the right AV groove could be a useful marker for differentiating the inflammatory status in obese men with MetS.

Coronary artery disease progression is associated with C-reactive protein and conventional risk factors but not soluble CD40 ligand.

BACKGROUND Coronary artery disease (CAD) is a major cause of death worldwide. Epidemiological studies have documented conventional risk factors; however, no studies to date have addressed the roles of soluble CD40 ligand (sCD40L) and monocyte chemoattractant protein-1 (MCP-1), and there have been few reports on other novel risk factors in CAD progression. The aim of the present study was to explore the roles of novel and conventional risk factors in CAD progression. METHODS Patients with stable angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of their first catheterization between March 1999 and January 2004 were enrolled. Those who had progression of coronary atherosclerosis were classified into the progression group (n = 66). Those who did not have CAD progression were classified into the nonprogression group (n = 124). RESULTS There were more cases of diabetes mellitus (36% versus 20%; P = 0.024) and more men (92% versus 81%; P = 0.040) in the CAD progression group than in the nonprogression group, respectively. The progression group also had poorer lipid profiles than the nonprogression group, including higher total cholesterol (188+/-42 mg/dL versus 173+/-39 mg/dL, respectively; P = 0.014) and low density lipoprotein cholesterol (122+/-38 mg/dL versus 112+/-36 mg/dL, respectively; P = 0.025). In terms of inflammatory markers, progression patients had higher baseline high-sensitivity C-reactive protein (hs-CRP) concentrations (P = 0.018), which was also related to the subsequent angiographic severity score changes; however, sCD40L (6182+/-4352 pg/mL versus 6244+/-4602 pg/mL; P = 0.961), MCP-1 (427+/-540 pg/mL versus 341+/-128 pg/mL; P = 0.580) and adhesion molecules concentrations were indifferent between the progression group and the nonprogression group, respectively. Using a multivariate logistical regression model, the ORs for predicting progression were 2.19 for diabetes mellitus, 2.04 for hypercholesterolemia and 1.52 for hs-CRP (P < 0.05). CONCLUSION In the present study, only conventional risk factors, and particularly hs-CRP, were markers for predicting CAD progression. Novel risk factors, such as concentrations of sCD40L, MCP-1 and adhesion molecules, did not play significant roles.