Hsiang-Chun Lee

JNK/ATF2 pathway is involved in iodinated contrast media-induced apoptosis.

Background/Aims: 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. Methods: 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. Results: 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. Conclusions: Differential activation of ATF2 by different contrast media provides a new insight into the mechanism and prevention of contrast-induced nephropathy.

Impact of short-duration administration of N-acetylcysteine, probucol and ascorbic acid on contrast-induced cytotoxicity.

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Acute Carbon Monoxide Poisoning Resulting in ST Elevation Myocardial Infarction: A Rare Case Report

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.

Myocardial performance index derived from brachial-ankle pulse wave velocity: a novel and feasible parameter in evaluation of cardiac performance.

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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Ionic contrast media induced more apoptosis in diabetic kidney than nonionic contrast media

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSION 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.

Terlipressin-related Acute Myocardial Infarction: A Case Report and Literature Review

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.

Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization.

BACKGROUND Slow delayed-rectifier potassium current (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 consequences of drug-induced KCNQ1 splice alteration remain unknown. OBJECTIVE To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes. METHODS 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 using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol. RESULTS With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram. CONCLUSIONS Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia.

Coronary Collateral Circulation in Patients of Coronary Ectasia with Significant Coronary Artery Disease

Objectives Patients with coronary ectasia (CE) usually have coexisting coronary stenosis resulting in myoischemia. Coronary collateral plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. However, limited studies investigate the role of CE in coronary collaterals development. Methods We evaluated 1020 consecutive patients undergoing coronary angiography and 552 patients with significant coronary artery disease (SCAD), defined as diameter stenosis more than 70%, were finally analyzed. CE is defined as the ectatic diameter 1.5 times larger than adjacent reference segment. Rentrop collateral score was used to classify patients into poor (grades 0 and 1) or good (grades 2 and 3) collateral group. Results 73 patients (13.2%) had CE lesions which were most located in the right coronary artery (53.4%). Patients with CE had a lower incidence of diabetes (43.8% vs 30.1%, p = 0.03), higher body mass index (25.4±3.5 vs 26.7±4.6, p = 0.027) and poorer coronary collateral (58.2% vs 71.2%, p = 0.040). Patients with poor collateral (n = 331) had a higher incidence of CE (15.7% vs 9.5%, p = 0.040) and fewer diseased vessels numbers (1.96±0.84 vs 2.48±0.69, p<0.001). Multivariate analysis showed diabetes (odd ratio (OR) 0.630, p = 0.026), CE (OR = 0.544, p = 0.048), and number of diseased vessels (OR = 2.488, p<0.001) were significant predictors of coronary collaterals development. Conclusion The presence of CE was associated with poorer coronary collateral development in patients with SCAD.

A CASE OF SUBARACHNOID HEMORRHAGE WITH PERSISTENT SHOCK AND TRANSIENT ST ELEVATION SIMULATING ACUTE MYOCARDIAL INFARCTION

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.

VLDL from Metabolic Syndrome Individuals Enhanced Lipid Accumulation in Atria with Association of Susceptibility to Atrial Fibrillation.

Metabolic syndrome (MetS) represents a cluster of metabolic derangements. Dyslipidemia is an important factor in MetS and is related to atrial fibrillation (AF). We hypothesized that very low density lipoproteins (VLDL) in MetS (MetS-VLDL) may induce atrial dilatation and vulnerability to AF. VLDL was therefore separated from normal (normal-VLDL) and MetS individuals. Wild type C57BL/6 male mice were divided into control, normal-VLDL (nVLDL), and MetS-VLDL (msVLDL) groups. VLDL (15 µg/g) and equivalent volumes of saline were injected via tail vein three times a week for six consecutive weeks. Cardiac chamber size and function were measured by echocardiography. MetS-VLDL significantly caused left atrial dilation (control, n = 10, 1.64 ± 0.23 mm; nVLDL, n = 7, 1.84 ± 0.13 mm; msVLDL, n = 10, 2.18 ± 0.24 mm; p < 0.0001) at week 6, associated with decreased ejection fraction (control, n = 10, 62.5% ± 7.7%, vs. msVLDL, n = 10, 52.9% ± 9.6%; p < 0.05). Isoproterenol-challenge experiment resulted in AF in young msVLDL mice. Unprovoked AF occurred only in elderly msVLDL mice. Immunohistochemistry showed excess lipid accumulation and apoptosis in msVLDL mice atria. These findings suggest a pivotal role of VLDL in AF pathogenesis for MetS individuals.