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ABSTRACT: BACKGROUND: IKs channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The drug-induced KCNQ1 splice alteration remains unknown. OBJECTIVE: We study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs currents and action potentials (AP) in ventricular myocytes. METHODS: We study the modulation of KCNQ1 splicing by amiloride and the consequent changes in IKs currents and action potentials (AP) in ventricular myocytes. Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by RT-PCR and Western blot. The impact of amiloride-induced alterations in KCNQ1b ratio on AP was measured using whole-cell patch clamp with and without isoproterenol. RESULTS: With 50 μmol/L amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increases in midmyocardial but decreases in endo- and epicardial myocytes. Likewise, changes of splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortens APD and decreases isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects are demonstrated by using human ventricular model for action potentials simulations under β-adrenergic stimulation. Moreover, amiloride reduces the transmural dispersion of repolarization in pseudo-ECG. CONCLUSIONS: Amiloride regulates IKs currents and action potentials with transmural differences and reduces arrhythmogenecity through modulating KCNQ1 splicing. We suggested that modulation of KCNQ1 splicing may prevent arrhythmia.
Heart rhythm: the official journal of the Heart Rhythm Society 04/2013; · 4.56 Impact Factor
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ABSTRACT: The best pharmaceutical prevention of contrast-medium-induced nephropathy for emergency procedures remains unknown. The aim of this study was to examine the impact of short-duration antioxidant pretreatment on contrast-medium-induced cytotoxicity.
Human embryonic kidney cells were treated with three different contrast media: ionic ioxitalamate, non-ionic low-osmolar iopromide, and iso-osmolar iodixanol. The doses and durations of pretreatment with antioxidants were 2 mM/L N-acetylcysteine for 15 minutes, 40 µM/L probucol for 30 minutes, and 30 µM/L ascorbic acid for 30 minutes. A supplementary dose of 2 mM/L N-acetylcysteine was administered 12 hours after contrast medium treatment. Cell viability was determined by tetrazolium MTT assay.
All three contrast media caused significant reduction of cell viability at 24 hours (p<0.001). In the groups receiving iopromide or iodixanol, N-acetylcysteine pretreatment significantly improved cell viability compared with no N-acetylcysteine pretreatment (p<0.001). In the group receiving ioxitalamate, N-acetylcysteine pretreatment followed by a supplementary dose of N-acetylcysteine at 12 hours rather than N-acetylcysteine pretreatment alone significantly improved cell viability compared with no N-acetylcysteine pretreatment (p=0.038). Probucol or ascorbic acid pretreatment was unable to reduce cell death caused by the three contrast media.
Short-duration pretreatment with N-acetylcysteine significantly reduced contrast-medium-induced cytotoxicity. These findings provide new insight into the prevention of contrast-medium-induced nephropathy in clinical emergency scenarios.
Journal of nephrology 04/2011; 25(1):56-62. · 1.65 Impact Factor
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ABSTRACT: Contrast-induced nephropathy is a major cause of hospital-acquired acute renal failure, and its risk is significantly increased in patients with diabetes mellitus. This study aimed to examine both the role of apoptosis in low-osmolar contrast media-induced kidney injury in normal and diabetic rats and the difference in the induced kidney injury between ionic and nonionic contrast media.
Normal and streptozotocin-induced diabetic Wistar rats were administered with ionic low-osmolar ioxaglate, nonionic low-osmolar iopromide or normal saline injection. Apoptosis in kidney tubular cells was determined by the presence of positive terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end-labeling (TUNEL) stain.
At 24 hours after administration, both ioxaglate and iopromide injections induced more apoptosis in diabetic (49.7% vs. 25.3% for ioxaglate; 37.7% vs. 25.3% for iopromide; both p<0.001) and normal (36.2% vs. 27.4%, p=0.002, for ioxaglate; 33.6% vs. 27.4%, p=0.029, for iopromide) kidney tubular cells than normal saline injections. Additionally, ioxaglate induced more apoptotic tubular cells in diabetic kidneys than in normal kidneys (p<0.001). Moreover, ioxaglate significantly induced more apoptotic cells than iopromide in diabetic kidneys, but not in normal kidneys (p<0.001, for diabetic rats; p=0.345, for normal rats).
Ionic low-osmolar contrast media induced more apoptosis in tubular cells in diabetic kidneys than in normal kidneys. Notably, ionic contrast media induced more apoptosis than nonionic contrast media in diabetic kidneys.
Journal of nephrology 10/2010; 24(3):376-80. · 1.65 Impact Factor
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ABSTRACT: Previous studies which included patients with preserved left ventricular (LV) systolic function demonstrated that arterial stiffness progressively increased as LV diastolic function decreased. However, it was unknown whether this correlation was still present in a heterogeneous study population involving patients with a wide range of LV systolic function. Seventy-five patients with depressed LV systolic function were consecutively included and 192 patients with preserved LV systolic function were randomly selected from subjects arranged for echocardiography examination. Brachial-ankle pulse wave velocity (baPWV) was measured using an ABI-form device. Of the 267 subjects (mean age 58 ± 14 years) included in the study, 105 had normal diastolic function, 74 had impaired relaxation, and 60 had pseudonormal and 28 restrictive diastolic dysfunction. BaPWV was only lower in patients with normal diastolic function than in those with abnormal diastolic function (p ≤ 0.001). It did not gradually rise as diastolic dysfunction grade increased. Multivariate analysis showed that increased age and systolic blood pressure and decreased LV ejection fraction, transmitral A velocity, and left atrial volume index (p ≤ 0.039) were correlated with increased baPWV. Our study showed that there were no positive correlation between echocardiographic LV diastolic parameters and baPWV. BaPWV did not progressively rise with increasing LV diastolic dysfunction grade. Therefore, patients with advanced LV diastolic dysfunction may not have increased arterial stiffness.
Heart and Vessels 10/2010; 25(6):485-92. · 2.05 Impact Factor
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ABSTRACT: Acute carbon monoxide (CO) poisoning with cardiac complications is well documented in the literature. However, ST segment elevation is a rare presentation, and most of these cases with ST elevation have revealed non-occlusive or normal coronary arteries. We report a case of CO poisoning complicated with ST elevation myocardial infarction. Emergency coronary angiography revealed total occlusion of the left anterior descending artery and primary percutaneous coronary intervention was performed. This report of a rare case should remind physicians that cardiovascular investigations, including electrocardiography, must be performed in cases with CO poisoning because mortality might increase if reperfusion therapy or appropriate medical treatments are not performed in patients with acute coronary artery occlusion.
The Kaohsiung journal of medical sciences 05/2010; 26(5):271-5. · 0.61 Impact Factor
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ABSTRACT: Notably, activating transcriptional factor 2 (ATF2), a histone-modification gene, is involved in oxidative stress-induced apoptosis. The aim of this study was to clarify the role of ATF2 in contrast media-induced nephropathy.
Human embryonic kidney 293T cells were treated with four different contrast media:ionic high-osmolar diatrizoate; ionic low-osmolar iothalamate; non-ionic low-osmolar iohexol, and non-ionic iso-osmolar iodixanol. The mRNA expression of ATF2 was determined by real-time PCR. Short interfering RNA was used to knock down ATF2 mRNA expression. Phosphorylation of ATF2 was measured by Western blotting. Wistar rats were administered either diatrizoate or a normal saline injection. Apoptosis in kidney tubular cells was determined by the presence of positive TUNEL stain.
Diatrizoate, iodixanol and iothalamate, but not iohexol, induced the expression of ATF2 mRNA and phosphorylation of ATF2 in 293T cells in a time-dependent manner. More apoptotic cells were in diatrizoate-treated kidney cells than in the saline injection group (p < 0.00001). Cell death was significantly increased by knockdown ATF2 expression in the presence of diatrizoate, indicating a protective role of ATF2 in contrast media-induced apoptosis.
Differential activation of ATF2 by different contrast media provides a new insight into the mechanism and prevention of contrast-induced nephropathy.
American Journal of Nephrology 11/2009; 31(2):125-33. · 2.54 Impact Factor
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ABSTRACT: Background Right brachial pre-ejection period (rbPEP), brachial–ankle pulse wave velocity (baPWV), and right brachial ejection time (rbET) can be automatically determined from an ABI-form device. The aims of this study are to test the applicability of baPWV-derived myocardial performance index (MPI) (defined as the ratio of rbPEP divided by its own s.d. + baPWV divided by its own s.d. to rbET divided by its own s.d.) as an indicator of combined left ventricular (LV) systolic and diastolic functions.
American Journal of Hypertension 05/2009; 22(8):871-876. · 3.18 Impact Factor
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ABSTRACT: Right brachial pre-ejection period (rbPEP), brachial-ankle pulse wave velocity (baPWV), and right brachial ejection time (rbET) can be automatically determined from an ABI-form device. The aims of this study are to test the applicability of baPWV-derived myocardial performance index (MPI) (defined as the ratio of rbPEP divided by its own s.d. + baPWV divided by its own s.d. to rbET divided by its own s.d.) as an indicator of combined left ventricular (LV) systolic and diastolic functions.
A sum of 215 patients were consecutively included. The rbPEP, baPWV, and rbET were measured using an ABI-form device and LV function was determined by echocardiography.
After a multivariate analysis, diastolic blood pressure (beta = 0.220, P < 0.001), LV ejection fraction (LVEF) (beta = -0.291, P < 0.001), transmitral E wave velocity (E) (beta = -0.106, P = 0.032), early diastolic mitral annular velocity (Ea) (beta = -0.142, P = 0.009), and ET obtained by tissue Doppler echocardiography (beta = -0.397, P < 0.001) were the major determinants of baPWV-derived MPI. The area under the curve for rbPEP, baPWV, rbET, rbPEP/rbET, and baPWV-derived MPI in prediction of Ea <8 cm/s, E/Ea >10, or LVEF <50% were 0.69, 0.76, 0.67, 0.73, and 0.83, respectively.
BaPWV-derived MPI had a significant correlation with echocardiographic LV diastolic and systolic function. It may be a novel and feasible indicator in assessment of global LV function.
American Journal of Hypertension 05/2009; 22(8):871-6. · 3.18 Impact Factor
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ABSTRACT: Mid-diastolic mitral annular motion may be driven by strain energy, an energy for myocardial recoil, stored during the previous systole. Hence, various patterns of mid-diastolic mitral annular motion may imply different left ventricular (LV) diastolic function. The purpose of this study is to compare LV diastolic properties among different types of mid-diastolic mitral annular motion. Two-hundred and three consecutive subjects underwent an echocardiographic examination at our outpatient clinic. Study subjects were classified into three groups according to mid-diastolic mitral annular motion patterns. Upward and downward La waves were defined, respectively, as a clear apically and atrially directed mid-diastolic annular motion on at least three consecutive beats with the average peak velocity > or =2 cm/s. Subjects with upward La wave, with downward but without upward La wave and without La wave were categorized as groups 1, 2 and 3, respectively. Early diastolic mitral annular velocity (Ea) was higher and the ratio of transmitral E wave velocity to Ea was lower in group 1 than in groups 2 and 3 (all p < 0.001). The diagnostic accuracy of upward La wave in prediction of normal diastolic function fell between 75% and 88%. In conclusion, patients with upward La wave had better LV diastolic function and lower LV filling pressure than patients without it. Upward La wave is useful in prediction of normal diastolic function. Therefore, analysis of mid-diastolic mitral annular motion may be complementary to other measures of LV diastolic function. (
Ultrasound in Medicine & Biology 06/2008; 34(5):753-9. · 2.29 Impact Factor
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ABSTRACT: Antioxidants such as N-acetylcysteine and probucol have been used to protect patients from contrast media-induced nephrotoxicity. The mechanisms underlying these protective effects are not well understood. We hypothesized that acetylcysteine and probucol alter the activity of endogenous antioxidant enzyme activity.
Four weeks after induction of diabetes with streptozotocin, diabetic and nondiabetic rats were divided into three groups. Group 1 rats did not receive any antioxidant agents. Group 2 rats were treated with acetylcysteine and group 3 rats with probucol for 1 week before injection of the contrast medium diatrizoate (DTZ).
We found that diabetic rats had higher renal glutathione peroxidase (GPx) activity than normal rats. DTZ suppressed renal GPx activity significantly in both group 1 diabetic and normal rats. Interestingly, renal GPx activity in both diabetic and normal rats pretreated with acetylcysteine or probucol was not inhibited by DTZ. Renal superoxide dismutase (SOD) increased significantly in normal rats after DTZ injection, but not in diabetic rats. Finally, acetylcysteine or probucol did not significantly influence renal SOD.
These findings suggest that the renal protective effects of acetylcysteine and probucol against contrast-induced oxidative stress and nephrotoxicity may be mediated by altering endogenous GPx activity.
Archives of Medical Research 05/2007; 38(3):291-6. · 1.88 Impact Factor
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ABSTRACT: We report a case of a 51-year-old diabetic male who presented with a complaint of intermittent chills and fever that he had experienced for 10 days. No obvious respiratory tract, genitourinary tract, gastrointestinal tract, or skin lesions were observed. Blood culture data were positive for group B beta-streptococcus. Transthoracic and transesophageal echocardiography revealed vegetation in the anterior leaflet of the mitral valve. The patient was diagnosed with infective endocarditis (IE) and prescribed a parenteral antibiotic. Three days after admission, the patient complained of progressively blurred vision. Slit lamp examination found fine keratic precipitates and aqueous cells in the anterior chambers in both eyes, implying that the patient had uveitis. He was then prescribed a topical steroid for 4 months, and his vision improved gradually. This case is an important reminder that uveitis, not only endophthalmitis, can occur with IE. Treatment for one condition, if misapplied, may worsen the other.
The Kaohsiung journal of medical sciences 02/2007; 23(1):40-4. · 0.61 Impact Factor
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ABSTRACT: Hemodynamic changes and contrast nephropathy are well known complications of contrast media injection. However, the mechanisms of toxicity leading to these complications remain unclear. We hypothesized that contrast media toxicity would manifest as a change in antioxidant enzyme activity, thus leading to tissue damage.
This study investigated the effects of injection of ionic high-osmolar diatrizoate, ionic low-osmolar ioxaglate, and nonionic low-osmolar iopromide on the activities of two antioxidant enzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), in the heart and kidney tissue of normal male Wistar rats (n = 51) and streptozotocin (STZ)-induced diabetic rats (n = 54). Activities of GPX and SOD were assayed spectrophotometrically.
Renal GPX activities were significantly decreased in both normal (458.3 +/- 64.6 to 385.5 +/- 63.4 mU/mg, p = 0.005) and diabetic rats (669.0 +/- 98.1 vs. 564.0 +/- 153.3 mU/mg, p = 0.035) at 1 hour after diatrizoate injection. Renal SOD activities were not affected after contrast injection. Ioxaglate and iopromide injection did not cause any change in renal antioxidant enzyme activity. In contrast to kidney tissue, there was no significant change in GPX and SOD activities in heart tissue at 1 hour after injection of different contrast media.
Intravenous injection of ionic high-osmolar diatrizoate reduced renal GPX activity during the first hour in both normal and STZ-induced diabetic rats. Heart tissue was not prone to antioxidant enzyme activity changes after intravenous contrast media injection. GPX activity reduction can be an important mechanism of nephrotoxicity after contrast media injection.
Journal of the Formosan Medical Association 08/2006; 105(7):530-5. · 1.13 Impact Factor
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ABSTRACT: Cardiac troponin I (cTnI) has been found to be a sensitive and reliable marker of myocardial damage, and elevated levels of cTnI can indicate high risk for acute coronary syndrome. To determine how to intervene in possible cases of acute coronary syndrome, cTnI levels must be measured by immunoassay. However, cTnI immunoassay results are prone to interference from many substances such as heparin and common drugs. The contrast media used in the coronary angiography might also interfere with results. To explore this possibility, we performed two in vivo and two in vitro studies. In the first in vivo study, we evaluated the effects of contrast media on cTnI immunoassays by collecting blood samples from 45 patients undergoing coronary angiography before and after the procedure. We used the Opus Magnum immunoassay system to measure cTnI levels. In the second in vivo study, we collected 25 blood samples from another group of patients also undergoing angiography at various times before and after the procedure to determine cTnI values by both the Opus Magnum and ACCESS systems. In the first in vitro study, 12 different contrast media were treated as samples to disclose the potential interference of measurement in the two assay systems. In the second in vitro study, we made sequential dilutions of iopromide (Ultravist; Schering) with serum to explore their potential for interfering with the detection of cTnI by the Opus Magnum and ACCESS assays. In the first in vivo study using the Opus Magnum assay, cTnI concentrations in samples taken after angiography were significantly higher at 5 minutes than at 30 minutes, and, at 60 minutes, all cTnI concentrations had dropped below the cutoff point. In the second in vivo study, we found a substantial difference in detection of cTnI by the Opus Magnum and ACCESS assays. All cTnI concentrations checked by ACCESS assay were below the cutoff value. In our first in vitro study, the Opus Magnum assay gave false positive results for all 12 contrast media; the ACCESS assay gave a positive result for only one contrast medium, poppy-seed oil (Lipiodol; Guebert). In our second in vitro study, we found that, in the Opus Magnum assay, the more concentrated the contrast medium, the higher the cTnI value, but not in the ACCESS assay. We conclude that contrast media may cause false-positive results in cTnI assays and that, when contrast media are being used for angiography, cTnI results, especially those based on samples taken within the first hour of the procedure, should be interpreted carefully.
The Kaohsiung journal of medical sciences 04/2006; 22(3):107-13. · 0.61 Impact Factor
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ABSTRACT: Acute ST-segment elevation myocardial infarction after the administration of terlipressin in patients with hemorrhagic esophageal varices is a rare but life-threatening complication. We report the case of a 73-year-old female patient with esophageal variceal bleeding complicated with acute ST-segment elevation myocardial infarction after intravenous injection of terlipressin. We discuss the underlying mechanisms of terlipressin-related acute myocardial infarction and review the literature.
The Kaohsiung journal of medical sciences 01/2005; 20(12):604-8. · 0.61 Impact Factor
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ABSTRACT: Electrocardiographic changes in neurovascular disease are not rare. Patients with subarachnoid hemorrhage have electrocardiographic (ECG) abnormalities that may mimic ischemic heart disease and acute myocardial infarction. Outflow of catecholamines in the early stage of subarachnoid hemorrhage contributes to elevated blood pressure in most patients. Hypotension is a rare presentation in subarachnoid hemorrhage. We report a case of subarachnoid hemorrhage with transient ST elevation and intractable shock simulating acute myocardial infarction, and review the mechanism of ECG changes in subarachnoid hemorrhage.
The Kaohsiung journal of medical sciences 10/2004; 20(9):452-6. · 0.61 Impact Factor
