Biomedical subjects

Yung-Zu Tseng

Publications and source records attributed to Yung-Zu Tseng.

At least 19 recordsLinked to original sources

PubMed2006

Renin-angiotensin system gene polymorphisms and coronary artery disease in a large angiographic cohort: detection of high order gene-gene interaction.

There have been many reports regarding the association between renin-angiotensin system (RAS) gene polymorphisms and coronary artery disease (CAD) or acute myocardial infarction (AMI), but the results are inconsistent. In the present study, we used several new approaches with multilocus data to reappraise this issue in a large and relatively homogeneous Taiwanese population. A total of 1254 consecutive patients who underwent cardiac catheterization (735 with documented coronary artery disease and 519 without) between 1996 and 2003 were recruited. Angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen gene; and A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In single-locus analyses, no locus was associated with CAD, history of AMI and three-vessel CAD, either with or without adjustment for conventional CAD risk factors. For multilocus analyses, we recreated a balanced population, with the controls individually matched to the cases regarding the conventional CAD risk factors. We found that the angiotensinogen gene haplotype profile was significantly different between the cases and controls (chi2=31.6, P=0.030) in haplotype analyses. Furthermore, significant three-locus (G-217A, M235T and I/D) gene-gene interactions were detected by multifactor-dimensionality reduction method (highest cross-validation consistency 10.0, lowest prediction error 40.56%, P=0.017) and many even higher order gene-gene interactions by multilocus genotype disequilibrium tests (16 genotype disequilibria exclusively found in the controls, all of which included at least two genes among AGT, ACE and AT1R genes). Our study is the first to demonstrate epistatic, high-order, gene-gene interactions between RAS gene polymorphisms and CAD. These results are compatible with the concept of multilocus and multi-gene effects in complex diseases that would be missed with conventional approaches.

Aged↗

PubMed2006

The association of human connexin 40 genetic polymorphisms with atrial fibrillation.

BACKGROUND: There is evidence showing that genetic factors contribute to the pathogenesis of atrial fibrillation (Af). We investigated the association between Af and polymorphisms of the connexin 40 (Cx40) gene, which is important in the electrical coupling between atrial myocytes. METHODS: We performed an association study between two Cx40 single nucleotide polymorphisms (SNPs) (Cx40 -44 and +71 allele) and Af. We enrolled 173 patients with Af, and the control group consisted of 232 patients without Af. The luciferase assay was performed to evaluate the promoter activities of different Cx40 haplotypes in cultured atrial myocytes. RESULTS: We found that the two SNPs were both significantly associated with Af. In pairwise linkage disequilibrium analysis, the two SNPs were completely linked (Cx40 -44G always associated with Cx40 +71A; Cx40 -44A associated with Cx40 +71G, P<0.001). In haplotype analysis, we demonstrated that the frequency of Cx40 (-44A,+71G) was significantly higher in the Af group than that in the control group (P<0.006, odds ratio=1.514, 95% confidence interval 1.13-2.04). We also performed genotype analysis using several genetic models, finding that the recessive model showed the lowest P value (P<0.004) and the largest odds ratio (2.53, 95% confidence interval 1.23-5.19). In promoter activity studies using luciferase as the reporter, Cx40 (-44A,+71G) had significantly lower promoter activity than that of the Cx40 (-44G,+71A) in atrial myocytes. CONCLUSIONS: The two SNPs in the promoter region of the Cx40 gene were significantly associated with Af. The Cx40 (-44A +71G) haplotype was associated with a higher risk for Af. This haplotype also had significantly lower promoter activity in atrial myocytes.

Aged↗

PubMed2006

Applications of 24-hour noninvasive ambulatory blood pressure monitoring.

Casual blood pressure (CBP) measurements using a standard sphygmomanometer have traditionally constituted the principal modality for the assessment and management of hypertension. However, CBP measurement has shortcomings. Ambulatory blood pressure monitoring (ABPM) provides abundant information on blood pressure (BP), including heart rate, all BP readings for test periods, BP average, BP variability, BP load, load index, distribution pattern of BP, reduction percentage of BP, trough/peak ratio, and summary statistics for overall 24-hour, daytime and nighttime periods. Over the last three decades, ABPM has evolved from a research device to an established and valuable clinical tool for assessment and management of hypertension. This technology has been proven to be useful in terms of the distribution pattern of BP, characterization of BP profiles in normotensive and hypertensive patients, evaluation of patients with mild or labile hypertension, physiologic and psychologic factors for fluctuation of BP, load index study, study of white coat hypertension, etiology of hypertension, prognosis of hypertension, and assessment of antihypertensive management. Nevertheless, the technology remains underused due to lack of insurance reimbursement in most countries. Accordingly, insurance reimbursement is crucial to promote increased utility of ABPM. Clinicians should be familiar with the role of this technology in the care of patients with abnormal BP. This review is an attempt to increase clinicians' understanding of ABPM and the appropriate use of this technology.

Blood Pressure Monitoring, Ambulatory↗

PubMed2006

Aminoguanidine prevents arterial stiffening and cardiac hypertrophy in streptozotocin-induced diabetes in rats.

The formation of advanced glycation endproducts (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study was to examine the role of aminoguanidine (AG), an inhibitor of AGEs formation, in the prevention of arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) induced diabetes in rats. Diabetes was induced in animals by a single tail vein injection with 65 mg kg(-1) STZ. After confirmation of the development of hyperglycemia (2 days later), rats were treated for 8 weeks with AG (daily peritoneal injections of 50 mg kg(-1)) and compared with the age-matched untreated diabetic controls. After exposure to AG, the STZ-diabetic rats showed no alterations in cardiac output, aortic pressure profiles, total peripheral resistance, and aortic characteristic impedance. By contrast, treatment of this experimental diabetes with AG resulted in a significant increase in wave transit time (tau), from 20.4+/-0.6 to 24.7+/-0.5 ms (P<0.05) and a decrease in wave reflection factor (R(f)), from 0.78+/-0.04 to 0.53+/-0.02 (P<0.05). The decreased R(f) associated with the increased tau suggest that AG may retard the diabetes-induced augmentation in systolic load of the left ventricle coupled to its arterial system. Meanwhile, the diminished ratio of left ventricular weight to body weight suggests that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening. Glycation-derived modification on aortic collagen was also found to be enhanced in rats with diabetes (+65.3%, P<0.05) and the advanced glycation process was retarded by AG treatment. We conclude that long-term administration of AG to the STZ-treated rats imparts significant protection against the diabetes-derived deterioration in vascular dynamics, at least partly through inhibition of the AGEs accumulation on collagen in the arterial wall.

Animals↗

PubMed2006

Using structural equation model to illustrate the relationship between metabolic risk factors and cardiovascular complications in Taiwan.

BACKGROUND: The objective of this study was to perform a population-based screening programme to determine the prevalence of the metabolic syndrome (MetS) and the relationship between metabolic risk factors and prevalent cardiovascular complications in Taiwan. DESIGN: A screening programme recruited residents aged 40 years and older in Sanchih, Taipei County, Taiwan, and collected demographic data, blood and urine samples. Fasting plasma glucose level, serum total cholesterol, high-density lipoprotein cholesterol, and triglyceride were measured. Atherosclerotic complications, including myocardial infarction, stress-positive angina, ischaemic stroke, and proteinuria were confirmed. METHODS: A structural equation model (SEM) was constructed to identify the association between metabolic abnormality and atherosclerosis. RESULTS: A total of 1494 subjects, 776 male and 718 female, were recruited in this study. The crude prevalence of the MetS was 19.3% for men [95% confidence interval (CI) 16.3-22.2%] and 18.7% for women (95% CI 15.6-22.0%). The presence of the MetS posed a substantial risk to microvascular complications in both sexes [odds ratio (OR) 3.29, P<0.001] and to macrovascular complications in men (OR 1.95, P=0.04) and also a trend in women (OR 2.24, P=0.089). There was a positive association between metabolic abnormality and atherosclerosis (B=0.55, P<0.001). CONCLUSIONS: This study has found the prevalence of the MetS and the association with atherosclerotic complications in Taiwan. The SEM approach has demonstrated a positive correlation between metabolic abnormality and atherosclerosis and can be used to explore new risk factors for cardiovascular diseases.

Adult↗

PubMed2005

Identification of good responders to rhythm control of paroxysmal and persistent atrial fibrillation by transthoracic and transesophageal echocardiography.

BACKGROUND: Identification of good responders to rhythm control in the management of atrial fibrillation (AF) is worthwhile in terms of increasing hemodynamic benefit and decreasing the likelihood of unstable anticoagulation even after the Atrial Fibrillation Follow-Up Investigation of Rhythm Management. METHODS: We tested the hypothesis that atrial substrate determines the risk of recurrence on rhythm control both in patients with paroxysmal AF (PAF) and in those with persistent or sustained AF (> or =1 week, SAF). There were 90 consecutive patients (mean age 63 +/- 12 years, 67 males and 23 females) with previous PAF (n = 66) or SAF (n = 24). They were maintained in sinus rhythm successfully for at least 1 month after conversion and then studied by transthoracic and transesophageal echocardiography. All of the patients were followed regularly by determination of symptoms, 12-lead ECG and intermittent Holter recording to determine recurrence of AF after echocardiographic study. RESULTS: After 9.1 +/- 3.8 (range 3-12) months of follow-up, 23 of the 90 (26%) patients had documented recurrence of AF (67 without recurrence). Univariate analysis of demographic characteristics, medications, ECG and echocardiographic parameters revealed that, compared with the group of patients without recurrent AF, the group of those with it included more members of the SAF group (11/27 vs. 13/67, p = 0.039), included more male subjects (22/23 vs. 45/67, p = 0.045), had a larger left atrial volume index (LAVI; 27 +/- 9 vs. 22 +/- 9 ml/m2, p = 0.024) and had lower LA appendage peak emptying velocity (LAAPEV; 42 +/- 15 vs. 55 +/- 22 cm/s, p = 0.01). Multivariate Cox proportional hazards regression analysis adjusted for age, gender and AF group revealed that patients with LAVI <30 ml/m2 and LAAPEV >46 cm/s had the least recurrence of AF (relative risk 0.18, 95% confidence interval 0.06-0.55, vs. with LAVI >30 ml/m2 or LAAPEV <46 cm/s, p = 0.002). Kaplan-Meier probability of freedom from AF recurrence was significantly better when LAVI <30 ml/m2 (log-rank p = 0.02), LAAPEV > 46 cm/s (p = 0.013) or both (p = 0.004). The superiority to predict the rate of sinus rhythm maintenance was the same in the PAF and SAF groups. CONCLUSIONS: Good responders to rhythm control in the PAF and SAF groups share the characteristics of smaller LA volume and better LAA contractile function, emphasizing the critical role of atrial substrate remodeling in recurrence of AF.

Adult↗

PubMed2005

Protection "outside the box" (skeletal remote preconditioning) in rat model is triggered by free radical pathway.

BACKGROUND: Remote preconditioning (RPC) for myocardial protection had been demonstrated in several organs, such as the kidney and mesentery artery. The aim of study was to investigate the effect of skeletal ischemia/reperfusion on coronary artery occlusion-induced myocardial infarction and to investigate the role of the free radicals. MATERIAL AND METHODS: RPC was performed in rats by a repeated four-cycle 10-min ischemia-reperfusion of femoral artery. Four experimental groups were included: I, sham group; II, RPC only; III, infarction only; and IV, which incorporated both RPC and infarction. A chemiluminescence study showed significant elevation of free radicals in groups with RPC, and pretreated mercaptopropionyl-glycine (MPG), a free radical scavenger, abolished the production of free radicals. RESULTS: The infarct size was significantly reduced for group IV (24.7 +/- 8.8%) compared with group III (51.4 +/- 9.1%; P < 0.001), and the effect was abolished by pretreatment with MPG (49.2 +/- 6.3% in MPG + III versus 50.1 +/- 8.2% in MPG + IV; P > 0.05). Cardiac enzymes also revealed significant decrease in the level for group IV compared with group III, and the protective effect could be abolished by MPG. Western blotting of heat shock protein (HSP) revealed that consistent elevation of HSP 25 and 70 in groups II, III, and IV, and the elevation can be abrogated by pretreatment with MPG. The expression of the antioxidant enzymes, Mn-superoxidase dismutase and glutathione peroxidase, in the area of risk were consistently elevated in groups II, III, and IV, similar to HSP. CONCLUSIONS: The skeletal RPC in rats can produce a protective effect in an infarction model that may be triggered through free radical pathway, and the protective effect was associated with HSP and antioxidant enzymes.

Animals↗

PubMed2005

Low frequency of target organ damage in Taiwanese with white coat hypertension.

BACKGROUND AND PURPOSE: The clinical importance of white coat hypertension (WCH) remains to be clarified. This study investigated the target organ damage in Taiwanese with WCH. METHODS: A total of 188 consecutive Taiwanese (88 men and 100 women), aged 26 to 75 years who had an abnormal office casual blood pressure (systolic blood pressure >/= 140 mm Hg or diastolic blood pressure >/= 90 mm Hg or both) and a normal ambulatory blood pressure (ABP) average (systolic ABP average < 140 mm Hg and diastolic ABP average < 90 mm Hg) at the outpatient clinic or from a mass survey were enrolled. Office casual blood pressure measurements were obtained by standard sphygmomanometric methods. Twenty-four-hour blood pressures were recorded by a commercial ambulatory pressure recorder (Del Mar Avionics, Model 1990 Pressurometer IV System). Hypertension-related target organ complications were assessed by electrocardiogram, chest X-ray, urinalysis and eye fundus examinations. RESULTS: Target organ damage was found in 6.4% of subjects with WCH. Roentgenographic left ventricular hypertrophy (LVH) was found in 1.1% of subjects and electrocardiographic LVH in 2.7%. Proteinuria was found in 1.6% of subjects and retinopathy in 1.1%. The frequencies of various target organ damage were not significantly associated with age, gender and the definition of normal ABP average as 135/85 mm Hg or 140/90 mm Hg. CONCLUSIONS: WCH represents a low-risk stratum for target organ damage in Taiwanese. These subjects should be identified and followed up regularly. The factors responsible for the low frequency of target organ damage in Taiwanese with WCH need further study.

Adult↗

PubMed2004

Aminoguanidine prevents age-related deterioration in left ventricular-arterial coupling in Fisher 344 rats.

In recent studies, aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that can prevent the age-related aortic stiffening and cardiac hypertrophy. The aim of this study was to determine whether AG had effects on the left ventricular (LV)-arterial coupling in aged Fisher 344 rats in terms of the ventricular and arterial chamber properties. Normotensive rats were treated from 18 to 24 months with AG (1 g l(-1) in drinking water) and compared with a control group. LV pressure and ascending aortic flow signals were recorded to construct the ventricular and arterial end-systolic pressure-stroke volume relationships to calculate LV end-systolic elastance (Ees) and effective arterial volume elastance (Ea), respectively. The optimal afterload (Qload) determined by the ratio of Ea to Ees was used to measure the efficiency of mechanical energy transferred from the left ventricle to the arterial system. In comparison with the 6-month-old rats, the 24-month-old animals had decreased Ees, at 567.4 +/- 26.7 vs 639.0 +/- 20.7 mmHg ml(-1), decreased Ea, at 411.5 +/- 18.6 vs 577.9 +/- 15.7 mmHg ml(-1), and decreased Q(load), at 0.9428 +/- 0.0024 vs 0.9962 +/- 0.0014. Treatment with AG for 6 months did not significantly affect Ees; however, when normalized to LV weight (i.e., Eesn = Ees/LV weight), Eesn showed a significant rise of 22.8%, suggesting that AG may retard the aging process on the intrinsic contractility of the left ventricle. On the other hand, the decrease in Ea in aging rats was prevented by AG, as reflected in the increase of 19.7% in this variable (P < 0.05). The 24-month-old treated rats also exhibited a significant rise of 21.6% in Ea/Ees, causing an increase of 5.2% in Qload (P < 0.05). We conclude that in healthy older Fisher 344 rats without diabetes, long-term treatment with AG may improve both the arterial and ventricular function and optimize the matching condition for the left ventricular-arterial coupling.

Aging↗

PubMed2004

Mitochondrial Na+ overload is caused by oxidative stress and leads to activation of the caspase 3- dependent apoptotic machinery.

Oxidative stress is one of the major causes of cell death. Using time-lapse confocal recording of live cardiomyocytes, we showed that H2O2 (OH*) caused a marked increase in Na+ and Ca2+ levels in both the cytosol ([Na]cyt, [Ca]cyt) and mitochondria ([Na]m, [Ca]m). The H2O2-induced intracellular Na+ ([Na]i) overload contributed to the H2O2-induced [Ca]cyt/[Ca]m overload via activation of the reverse mode of the Na-Ca exchanger. When myocytes were treated for 40 min with 100 microM H2O2 in normal medium, then returned to H2O2-free medium, the percentage of apoptotic cells increased from 4% at 0 h to 55 and 85% at 4.5 and 16 h, respectively. H2O2-induced apoptosis was completely prevented by using Na-free, but not Ca-free, medium. When a Na+ ionophore cocktail in Ca-free medium was used instead of H2O2 to increase the [Na]i by more than 30 mM without any change in the [Ca]i, cytochrome c release and caspase 3-dependent apoptosis occurred, showing that [Na]i overload per se induced apoptosis. We also showed that the increase in the mitochondrial, but not the cytosolic, Na+ levels resulted in the opening of the permeation transition pore, followed by cytochrome c release. Our findings therefore suggest that H2O2-induced [Na]m overload is an important upstream signal for the apoptotic machinery, and the prevention of [Na]m overload thus represents a particularly attractive target for strategies aimed at preventing oxidative stress-induced cell death.

Apoptosis↗

PubMed2004

Three single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension: single locus genotype vs. haplotype analysis.

Although some single polymorphism analyses of the angiotensinogen (AGT) gene have been found to be associated with hypertension, the results are still inconsistent. The objectives of this study are to evaluate the association of the genotype and haplotype distributions of three single-nucleotide polymorphisms (SNPs) (G-217A, A-6G, and M235T) in the AGT gene with hypertension. In a sample of 461 hypertensive and 327 normotensive patients in Taiwan, we found that -217AA and -6GG homozygotes conferred independently an increased risk to hypertension (P = 0.008 and P = 0.037, respectively), as illustrated by their significant associations with hypertension in both single SNP and pair-wise SNPs analyses. Meanwhile, a very weak linkage disequilibrium was found between the G-217A and the A-6G polymorphisms in terms of r2 (<0.05). On the basis of likelihood ratio test, only the set of haplotypes that constituted the A-6G and the M235T polymorphisms was associated with hypertension (chi2 = 20.91, P = 0.0008), which was mainly due to the increased frequency of the recombinant haplotypes (-6A identical with 235M and -6G identical with 235T), and a pathophysiological role in the predisposition to hypertension was hence indicated. In functional assays, the promoter activities of the haplotypes -217A identical with -6A and -217G identical with -6G were significantly higher than the most common haplotype -217G identical with -6A. These results highlight the necessity of a thorough analysis of all reported variants of a candidate gene in the elucidation of genetic susceptibility to a complex disease like hypertension, even when the variants are in the same haplotype block.

Angiotensinogen↗

PubMed2004

Renin-angiotensin system gene polymorphisms and atrial fibrillation.

BACKGROUND: The activated local atrial renin-angiotensin system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation (AF). We hypothesized that RAS genes might be among the susceptibility genes of nonfamilial structural AF and conducted a genetic case-control study to demonstrate this. METHODS AND RESULTS: A total of 250 patients with documented nonfamilial structural AF and 250 controls were selected. The controls were matched to cases on a 1-to-1 basis with regard to age, gender, presence of left ventricular dysfunction, and presence of significant valvular heart disease. The ACE gene insertion/deletion polymorphism, the T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen gene, and the A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In multilocus haplotype analysis, the angiotensinogen gene haplotype profile was significantly different between cases and controls (chi2=62.5, P=0.0002). In single-locus analysis, M235T, G-6A, and G-217A were significantly associated with AF. Frequencies of the M235, G-6, and G-217 alleles were significantly higher in cases than in controls (P=0.000, 0.005, and 0.002, respectively). The odds ratios for AF were 2.5 (95% CI 1.7 to 3.3) with M235/M235 plus M235/T235 genotype, 3.3 (95% CI 1.3 to 10.0) with G-6/G-6 genotype, and 2.0 (95% CI 1.3 to 2.5) with G-217/G-217 genotype. Furthermore, significant gene-gene interactions were detected by the multifactor-dimensionality reduction method and multilocus linkage disequilibrium tests. CONCLUSIONS: This study demonstrates the association of RAS gene polymorphisms with nonfamilial structural AF and may provide the rationale for clinical trials to investigate the use of ACE inhibitor or angiotensin II antagonist in the treatment of structural AF.

Aged↗

PubMed2004

Mechanism of oleic acid-induced gap junctional disassembly in rat cardiomyocytes.

This study investigated the mechanism of oleic acid (OA) on gap junctions and identified the protein kinase C (PKC) isoforms involved in OA-mediated gap junction disassembly in cardiomyocytes. Control cardiomyocytes showed continuous staining of the plasma membrane at cell-cell contact areas using antibodies reacting with connexin 43 (Cx43). The spontaneous contraction rate of cultured cardiomyocytes was reduced in a time-dependent manner by OA. In addition, Cx43 expression at cell-cell junction decreased, suggesting the disassembly of gap junction. Staining for PKC and PKCalpha, which were shown to colocalize with Cx43, also decreased with increased duration of OA treatment. The effects of OA on these distributional changes at cell junctions were reversed by 24 h incubation in fresh culture medium devoid of OA. Immunoprecipitation assays confirmed the biochemical binding between Cx43 and PKC/PKCalpha, and this protein interaction was not affected by OA. This may provide the basis for simultaneous detachment of Cx and PKC/PKCalpha from the cell-cell junction to the cytosol upon OA stimulation. Western blot analysis showed that OA-induced Cx43 Ser368 phosphorylation, and that this effect could be blocked by cotreatment with the general PKC inhibitor, calphostin C, the PKC inhibitor, eV1-2, or the Src kinase inhibitor, PP1, but not by the PKCalpha inhibitor, Gö6976. eV1-2 also prevented the OA-induced disassembly of gap junctions. Taken together, these data suggest that OA-induced Cx43 Ser368 phosphorylation is mediated by activation of PKC and Src kinase and might be responsible for OA-induced gap junctional disassembly.

Animals↗

PubMed2004

Restoration of heart rate turbulence by titrated beta-blocker therapy in patients with advanced congestive heart failure: positive correlation with enhanced vagal modulation of heart rate.

INTRODUCTION: Heart rate turbulence (HRT) is a powerful novel predictor for cardiovascular mortality. Chronic congestive heart failure is associated with abnormal HRT. Whether antiadrenergic beta-blocker therapy can restore control of HRT in patients with chronic congestive heart failure is unknown. METHODS AND RESULTS: A 24-hour Holter ECG recording was obtained before and 1 and 3 months after titrated addition of atenolol therapy in 10 consecutive patients with advanced congestive heart failure. Two parameters derived from HRT, turbulence slope (TS) and turbulence onset (TO), and time- and frequency-domain heart rate variability (HRV) parameters (SDNN, RMSSD, VLF, LF, HF) from 24-hour ECG were compared before and after beta-blocker therapy, together with the same parameters in age-matched normal control. Results showed that TS (3.1 +/- 2.2 vs 6.2 +/- 3.0; P = 0.001) and all HRV parameters were increased after 3 months of atenolol treatment. No changes in TO were evident (0.6 +/- 0.5 vs -0.2 +/- 1.3; P = 0.13). The improvement of TS and the vagally mediated parameters of mean R-R interval, RMSSD, and the HF component of HRV were positively correlated. CONCLUSION: Abnormal HRT caused by chronic congestive heart failure can be restored by beta-blocker therapy. The evolution of TS was positively correlated with measures of vagal modulation of heart rate.

Adrenergic beta-Antagonists↗

PubMed2004

Functional genomic study on atrial fibrillation using cDNA microarray and two-dimensional protein electrophoresis techniques and identification of the myosin regulatory light chain isoform reprogramming in atrial fibrillation.

INTRODUCTION: Functional and structural changes of atrial tissue occur during the natural course of atrial fibrillation (AF), and these changes may contribute to further AF. We investigated the changes in AF tissue using cDNA microarray and two-dimensional protein electrophoresis techniques. METHODS AND RESULTS: We established a porcine model of AF by rapid right atrial appendage pacing at a rate of 600/min. Atrial tissue was obtained after rapid atrial depolarization for 6 weeks. Microarrays containing 6,035 cDNA clones were used to evaluate the alterations of mRNA. Two-dimensional protein electrophoresis was performed to compare protein patterns. In cDNA microarray studies, we identified 387 genes with significant change in the left atrium and 81 genes in the right atrium. Among the genes, the ventricular isoform of the myosin regulatory light chain (MLC-2V) showed the greatest fold of change (9.4 and 7.3 in the left and right atrium, respectively). In protein electrophoresis, the expression levels of three protein spots spanning from 18 to 20 kDa in the acidic region (PI 4.5-5.0) were specifically elevated in the AF group. Interestingly, through tandem mass spectrometric analysis, these three spots were identified as MLC-2V. Thus, MLC-2V expression at the mRNA and protein levels corresponded well, and both indicated a significant increase in AF. CONCLUSION: Both cDNA microarray and two-dimensional polyacrylamide protein electrophoresis studies revealed characteristic changes in AF tissue. We demonstrated the reprogramming of myosin regulatory light chain isoform composition, with a significant increase of its ventricular isoform (MLC-2V).

Animals↗

PubMed2004

Use of double-potential barrier to identify functional isthmus at the cavotricuspid isthmus for facilitating catheter ablation of isthmus-dependent atrial flutter.

INTRODUCTION: The aim of the study was to identify an alternative target for more effective radiofrequency catheter ablation (RFCA) of isthmus-dependent atrial flutter (AFL). METHODS AND RESULTS: We hypothesized that a functional isthmus formed by preexisting double potential barrier at the cavotricuspid isthmus (CTI) could serve as a new target site for facilitating RFCA of AFL. Forty-three consecutive patients with recurrent isthmus-dependent AFL were studied using three-dimensional navigated magnetic mapping and ablation technique. Twenty patients (47%, group A) were shown to have a narrower functional channel at the CTI (functional isthmus). The remaining 23 patients did not have this feature (53%, group B). In group A, double potentials were clustered near the border of the inferior vena cava (IVC) of the CTI and served as a functional channel along the tricuspid annulus (TA). The interspike interval of double potentials was 87 +/- 26 ms near the IVC border and 45 +/- 17 ms (P < 0.0001) near the TA border of CTI. RFCA targeting at the functional isthmus in group A resulted in interruption of bidirectional transisthmus conduction with fewer radiofrequency pulses (6.7 +/- 4.7 in group A vs 21.1 +/- 17.1 pulses in group B, P < 0.001), shorter ablation line (11.6 +/- 4.0 mm vs 37.8 +/- 7.2 mm, P < 0.0001) with no arrhythmia recurrence. These functional isthmuses were found to be located at the lateral third of CTI in 12 patients, middle third in 7, and medial third in 1. This finding is different from that obtained by the conventional method in group B (lateral in 5, middle in 16, medial in 2, P < 0.038). CONCLUSION: In our study, a functional, rather than anatomic, isthmus formed by preexisting double-potential barrier at the CTI was identified in 47% of patients with isthmus-dependent AFL. It is a useful guide to facilitate RFCA of isthmus-dependent AFL.

Atrial Flutter↗

PubMed2004

P wave separation after atrial compartment operation for atrial fibrillation.

Surgically induced abnormalities in atrial conduction could result in unusual P wave changes. A 31-year-old woman underwent concomitant mitral valve surgery and atrial compartment operation for mitral stenosis and atrial fibrillation (AF). After operation, the AF was successfully converted to sinus rhythm, whereas an unusual electrocardiogram (ECG) with a discrete negative deflection before the T wave in V1 was noted. Electrophysiological study showed a marked conduction delay from the high right atrium (HRA) to the right atrial appendage (RAA) compartment, which resulted in a separation of P waves. The P wave preceding the QRS complex represented the activation of sinus node and the left atrial compartments, and the P at the vicinity of T wave represented the activation of RAA compartment. The conduction from HRA to RAA was worsened on HRA pacing at a faster rate, and improved after isoproterenol infusion. This report demonstrated that conduction across a surgically created isthmus in the atrium could be severely impaired and result in unusual P wave separation.

Adult↗

PubMed2004

Aminoguanidine prevents fructose-induced arterial stiffening in Wistar rats: aortic impedance analysis.

Fructose has been reported as a potent agent in forming advanced glycation end products (AGEs) and, thus, may play a significant role in the pathogenesis of diabetic complications. Herein, we determined the effects of aminoguanidine (AG), an inhibitor of AGEs, on the mechanical properties of the arterial system in fructose-fed (FF) rats, using aortic impedance analysis. Rats at 2 months were given 10% fructose in drinking water for 2 weeks and compared with untreated age-matched controls. Meanwhile, FF rats were treated for 2 weeks with AG (daily peritoneal injections of 50 mg kg(-1)) and compared with the untreated FF group. Neither fructose nor AG affects body weight, blood glucose level, and basal heart rate. In comparison with controls, FF rats showed a decrease in cardiac output in the absence of any significant changes in mean aortic pressure, having increased total peripheral resistance (R(p)), at 51.1 +/- 2.9 versus 66.2 +/- 1.9 mm Hg sec ml(-1) (P < 0.05). Fructose also contributed to an increase in aortic characteristic impedance (Z(c)), from 1.528 +/- 0.094 to 1.933 +/- 0.084 mm Hg sec ml (-1) (P < 0.05) and a decrease in wave transit time (tau), from 22.6 +/- 0.6 to 19.2 +/- 0.7 msec (P < 0.05). The elevated Z(c) and the reduced tau suggest that fructose may cause a detriment to the aortic distensibility in animals. After exposure to AG, FF rats exhibited a significant improvement in physical properties of the resistance vessels, as evidenced by the reduction of 21.3% in R(p). Meanwhile, AG retarded the fructose-induced decline in aortic distensibility, as reflected in the decrease of 16.0% in Z(c) (P < 0.05) and the increase of 18.1% in tau (P < 0.05). By contrast, AG exerted no effects on the mechanical properties of Windkessel vessels, as well as resistance vessels, in normal diet controls. We conclude that AG may prevent the fructose-derived changes in arterial stiffening, possibly through inhibition of the fructose-derived advanced glycation end product formation in Wistar rats.

Animals↗