Images in cardiology. Asymptomatic coronary artery aneurysm associated with paclitaxel eluting stent.
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Cardiovascular Agents↗
Biomedical subjects
J K Ko
Publications and source records attributed to J K Ko.
The role of exercise training for patients with heart failure.
Heart failure (HF) is characterized by dyspnea and fatigue leading to exercise intolerance. HF patients have been advised to avoid exercise because of concerns about detrimental cardiac effects. However, in many studies on the effects of exercise training HF patients have demonstrated beneficial outcomes. Furthermore, exercise training has been found to be safe. Recent studies have demonstrated that exercise training might reduce morbidity and mortality. Although these data are promising, confirmation is required from a large clinical trial powered to examine the effects of exercise training on mortality and morbidity. The "Heart Failure - A Controlled Trial Investigating Outcomes of Exercise TraiNing" (HF-ACTION) trial, a large randomized controlled clinical trial, will answer that question. Standardized guidelines for exercise training HF patients have not been established. Exercise training should be individualized according to the results of the exercise test. Ideally, the exercise program should be initiated in the setting of a supervised program followed by a home-based program. Each patient should have a tailored activity program based on a prescription for the frequency of each session, the intensity, duration of each session, and modalities to be used. Exercise training should involve aerobic exercise. Resistance exercise and interval training might be an acceptable method for HF patients; however, more studies are required for these types of exercise programs.
Exercise Therapy↗
Long-term efficacy of atenolol for atrioventricular reciprocating tachycardia in children less than 5 years old.
Atrioventricular reciprocating tachycardia (AVRT) using an accessory pathway is the most common supraventricular tachycardia observed in infancy and childhood. There is a general agreement to treat children older than 5 years who are on a potentially long-term antiarrhythmic agent with radiofrequency catheter ablation. Atenolol, a relatively long-acting and cardioselective beta-adrenoceptor blocker, has been used to control the various types of supraventricular tachycardia in children and adults. There are few reports on the use of atenolol in children <5 years old with AVRT. This retrospective study reports our experience in 22 children <5 years old (median age, 20 months) who received atenolol monotherapy between 1995 and 2001 for treatment of AVRT. AVRT was confirmed in 17 patients by transvenous or transesophageal electrophysiologic study and in 5 patients by documented preexcitation on electrocardiograms. In nine patients atenolol was the first antiarrhythmic drug given. In 15 of the 22 patients (68%) therapy with atenolol was considered successful. The average effective dose of atenolol in these 15 patients was 1.2 +/- 0.3 mg/kg/day. During a median follow-up of 41 months (8-74 months), atenolol had been discontinued in 10 patients and no further attacks of tachycardia occurred except in 1 patient. In no case did the drug have to be withdrawn for adverse effects. In conclusion, this retrospective study shows that atenolol as a monotherapy is efficient and relatively safe in the long-term treatment of AVRT in young children. Atenolol can be recommended as a first-line treatment option for the management of AVRT in infants and young children.
Adrenergic beta-Antagonists↗
Inducible RGS2 is a cross-talk regulator for parathyroid hormone signaling in rat osteoblast-like UMR106 cells.
Parathyroid hormone (PTH) activates dual signal transduction systems via Galphas and Galphaq proteins. We now report a novel mechanism by which "cross-talk" may occur between the Galphas and Galphaq signaling pathways. RGS2 (Regulator of G protein Signaling 2) mRNA was rapidly and transiently increased only by PTH analogs (PTH1-84, 1-34, 1-31, and PTHrP) that activated the Galphas-mediated cAMP/PKA signaling pathway, whereas activation of the Galphaq-mediated Ca(2+)/PKC signaling pathway by PTH3-34 had no effect on RGS2 expression. Treatment of UMR106 cells with nonPTH activators of the cAMP/PKA signaling pathway such as cholera toxin, forskolin, 8-Br-cAMP, and dibutyryl-cAMP also significantly elevated RGS2 mRNA levels, while activator of the Galphaq pathway PMA did not. Pretreatment using the Galphas signaling pathway inhibitors SQ22536 and H89 significantly blocked PTH-induced RGS2 expression, but the Galphaq signaling pathway inhibitor bisindolylmaleimide I had no effect. Therefore, RGS2 expression is governed solely by the Galphas signaling pathway. Additionally, we demonstrate for the first time that RGS2 binds to both Galphas and Galphaq subunits in their transition state (GDP/AlF(-4)-bound) forms, suggesting that RGS2 has the potential to act as a bridge between the cAMP/PKA and Ca(2+)/PKC pathways, and that it may act as a cross-talk regulator for these two PTH signaling pathways.
Animals↗
Protective role of cyclooxygenase inhibitors in the adverse action of passive cigarette smoking on the initiation of experimental colitis in rats.
Clinical and experimental findings had indicated that cigarette smoke exposure, and cyclooxygenase-2, are strongly associated with inflammatory bowel disease. The present study aimed to evaluate the role of cyclooxygenase-2 in the pathogenesis of experimental inflammatory bowel disease as well as in the adverse action of cigarette-smoke exposure. Rats were pretreated with different cyclooxygenase-2 inhibitors (indomethacin, nimesulide, or SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide)) along with cigarette-smoke exposure before 2,4,6-trinitrobenzenesulfonic acid-enema. Results indicated that pretreatment with cyclooxygenase-2 inhibitors not only protected against 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also attenuated the potentiating effect of cigarette-smoke exposure on colonic damage. Furthermore, the colonic cyclooxygenase-2 protein and mRNA expression was markedly induced by 2,4,6-trinitrobenzenesulfonic acid-enema, and it was potentiated further by cigarette-smoke exposure, while the cyclooxygenase-1 expression was not changed. The present study suggests that the highly induced cyclooxygenase-2 expression not only plays a pathogenic role in 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also contributes to the adverse action of cigarette-smoke exposure on this disorder.
Animals↗
Signal transduction of nitric oxide donor-induced protection in hydrogen peroxide-mediated apoptosis in H9C2 cardiomyoblasts.
Nitric oxide (NO) attenuates hydrogen peroxide (H2O2)-mediated injury to H9C2 cardiomyoblasts. To examine the role of nitric oxide, cultured H9C2 cardiomyoblasts were treated with H2O2 for 2 h in the presence or absence of the NO donor, diethylamine nitric oxide (DEANO). DEANO (30 microM) attenuated H2O2-induced apoptosis in H9C2 cells. H2O2-exposed H9C2 cells resulted in apoptosis in a time-dependent manner estimated by DNA fragmentation assay, nuclear morphology stained with fluorescent dye, Hoechst 33258 and Annexin V staining. Pretreatment with z-VAD-FMK, a pancaspase inhibitor, or z-DEVD-CHO, a specific caspase-3 inhibitor, completely suppressed the DNA ladder in response to H2O2. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. Treatment of H9C2 cells with 100 microM H2O2, resulted in a strong activation of JNK/SAPK. However, the activation of JNK/ SAPK was clearly attenuated by 30 microM DEANO. Furthermore, the dominant negative JNK and SEK1-expressing cells displayed a marked decrease in a number of apoptotic cells. This inhibition of JNK1 in the system is involved in the protection of H2O2-induced apoptosis in H9C2 cardiomyoblasts.
Animals↗
Aggravating effect of cigarette smoke exposure on experimental colitis is associated with leukotriene B(4) and reactive oxygen metabolites.
BACKGROUND/AIMS: Cigarette smoking is closely related to the development and recurrence of inflammatory bowel disease (IBD). The present study aimed to investigate the underlying mechanisms of the adverse action of cigarette smoke (CS) exposure on trinitrobenzene sulfonic acid (TNBS)-induced IBD. METHODS: Rats were preexposed to CS once daily for 4 days before receiving a TNBS enema, and they were killed 24 h afterwards. The colonic myeloperoxidase (MPO) and xanthine oxidase (XO) activities, leukotriene B(4) (LTB(4)) and glutathione (GSH) levels, as well as the production of reactive oxygen metabolites (ROMs) were measured. RESULTS: CS preexposure significantly augmented the adverse effects of the TNBS enema on colonic damage and increase in MPO activity, while it did not significantly alter the XO activity. Meanwhile, the elevation of ROM production and LTB(4) concentration in colonic tissues after the TNBS enema was also markedly enhanced by CS exposure. In contrast, the depressive action of the TNBS enema on cellular antioxidant GSH levels was reduced further by CS exposure. Pretreatment with a specific LTB(4) antagonist, ONO-4057, protected against colonic damage, particularly in the CS group. CONCLUSION: CS exposure aggravated experimental IBD. This adverse action could be due to the depletion of GSH together with overproduction of LTB(4), followed by the accumulation of neutrophils and ROMs in the colonic tissue.
Analysis of Variance↗
Beneficial intervention of experimental colitis by passive cigarette smoking through the modulation of cytokines in rats.
BACKGROUND: Epidemiologic observations have indicated that cigarette smoking decreases the risk of ulcerative colitis, but the modes of action remain anonymous. The present study aimed to investigate the beneficial effects of passive cigarette smoking using an animal colitis model. We hypothesized that the underlying mechanisms may involve immunoregulation of cytokines. METHODS: Experimental colitis was induced in rats by enema administration of 2,4-dinitrobenzene sulfonic acid (DNBS). Passive cigarette smoking by rats was performed for 1 hour once daily, from 3 days before DNBS enema until they were sacrificed on day 8. Other groups of DNBS-treated rats received therapeutic treatment of cyclosporin A or pentoxifylline, a tumor necrosis factor (TNF)-alpha inhibitor. Macroscopic and histologic damage were graded, and the colonic levels of different cytokines and the levels/activities of parameters related to neutrophil activation were also measured. RESULTS: DNBS-induced colonic damage was improved in passive-cigarette-smoking rats. This was accompanied by attenuation of the elevated colonic myeloperoxidase and inducible nitric oxide synthase activities and leukotriene B4 level. Likewise, the augmentation in colonic levels of TNF-alpha, interleukin (IL)-1 beta, and IL-6 in colitis rats was also alleviated by passive cigarette smoking. In contrast, the deprivation of colonic IL-10 during colitis was preserved in cigarette-smoking rats. These effects were similarly accomplished by pentoxifylline and, to some degree, by cyclosporin A. CONCLUSIONS: The results support the idea that the beneficial effects of passive cigarette smoking in experimental colitis involved immunoregulation of cytokines in colonic tissues.
Animals↗
Coadministration of angiopoietin-1 and vascular endothelial growth factor enhances collateral vascularization.
Using growth factors to induce vasculogenesis is a promising approach in the treatment of ischemic legs and myocardium. Because the vasculogenesis requires a cascade of growth factors, their receptors, and intracellular signals, such therapies may require the application of more than a single growth factor. We examined the effect of 2 endothelial cell-specific growth factors, angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), on primary cultured porcine coronary artery endothelial cells. VEGF, but not Ang1, increased DNA synthesis and cell number. Ang1 or VEGF induced migration and sprouting activity, increased plasmin and matrix metalloproteinase-2 secretion, and decreased tissue inhibitors of metalloproteinase type 2 secretion. A combination of the submaximal doses of Ang1 and VEGF enhanced these effects and was more potent than the maximal dose of either alone. In a rabbit ischemic hindlimb model, a combination of Ang1 and VEGF gene delivery produced an enhanced effect on resting and maximal blood flow and capillary formation that was greater than that of either factor alone. Angiographic analyses revealed that larger blood vessels were formed after gene delivery of Ang1 or Ang1 plus VEGF than after VEGF gene delivery. These results suggest that combined treatment of Ang1 and VEGF could be used to produce therapeutic vascularization.
Angiopoietin-1↗
Alcohol drinking and cigarette smoking: a "partner" for gastric ulceration.
Alcohol consumption and cigarette smoking are two etiologic factors that have a close relationship with peptic ulcer diseases. Chronic active gastritis is reportedly associated with chronic alcohol ingestion. Nonetheless, the inflammatory changes are likely to be related to concurrent Helicobacter pylori infection that is common among alcoholics. Moreover, chronic alcoholism is also correlated with the presence of gastric metaplasia. Both clinically and experimentally, alcohol had been shown to affect the mucosal barrier and histology. These ulcerogenic effects play a crucial role in altering gastric mucosal defense mechanisms. Cigarette smoking is coupled with the initiation and prolongation of gastric ulcers. Epidemiologic data show that cigarette smoking increases both the incidence and relapse rate of peptic ulcer diseases and also delays ulcer healing in humans. Retrospective studies also indicate that cigarette smoking is a key factor in inducing ulcer diseases rather than a linked behavior. The general detrimental effects of cigarette smoking in the gastric mucosa include reduction of circulating epidermal growth factor, increase in tissue free radical production and the presence of free radicals in smoke, together with reduction of mucosal constitutive nitric oxide synthase activity. Furthermore, the alteration of normal gastric mucosal blood flow and angiogenesis and the suppression of cell proliferation contribute largely to the delay in ulcer healing in cigarette smokers. Concurrent consumption of alcohol and cigarette smoking significantly increases the risk of gastric ulcers. In animal experiments, cigarette smoking potentiated ethanol-induced gastric mucosal damage. The reduction of mucus secretion, increase in leukotriene B4 level, increased activities of inducible nitric oxide synthase, xanthine oxidase and myeloperoxidase, and the expression of adhesion molecules in the gastric mucosa accompanied such potentiating effects. Substances other than nicotine in cigarette smoke may also contribute to the above effects.
Alcohol Deterrents↗
Co-regulation of mucosal nitric oxide and prostaglandin in gastric adaptive cytoprotection.
OBJECTIVE: The correlation between mucosal generation of nitric oxide (NO) and prostaglandin E2 (PGE2) in gastric adaptive cytoprotection was investigated. MATERIALS AND TREATMENT: Male Sprague-Dawley rats were pretreated with either N(w)-nitro-L-arginine methyl ester (L-NAME, 12.5 mg/kg i.v.) or indomethacin (5 mg/kg s.c.). Following that, mild irritant 20% ethanol was administered, 15 min prior to 100% ethanol challenge. METHODS: Macroscopic gastric mucosal damage, NO synthase activity, mucosal PGE2 and leukotriene C4 (LTC4) levels were measured. RESULTS: Administration of L-NAME and indomethacin significantly reduced the protective action of 20% ethanol against 100% ethanol-induced gastric mucosal damage. Besides, mucosal activity of constitutive NO (cNO) synthase, but not of the inducible isozyme (iNO synthase), was elevated following 20% ethanol treatment. This was accompanied by a reduction in mucosal leukotriene C4 level. Indomethacin significantly inhibited mucosal PGE2 biosynthesis but increased cNO synthase activity. Nevertheless, L-NAME reduced both cNO and iNO formation and prevented the increase in cNO formation caused by 20% ethanol, while enhancing mucosal PGE2 production. Combined L-NAME and indomethacin treatment markedly potentiated ethanol-induced mucosal damage, and completely prevented the increase in cNO or PGE2 biosynthesis when either compound was given alone. CONCLUSIONS: These findings suggest a co-regulatory relationship between mucosal NO and PG in the gastric defense system, which will be released after activation by the mild irritants to induce cytoprotection.
Animals↗
Involvement of neutrophils and free radicals in the potentiating effects of passive cigarette smoking on inflammatory bowel disease in rats.
BACKGROUND & AIMS: Cigarette smoking is associated with inflammatory bowel diseases (IBDs), particularly Crohn's disease, in humans. The aim of this study was to examine whether passive cigarette smoking aggravates experimental IBD in rats and to clarify the underlying mechanisms. METHODS: Rats were exposed to cigarette smoke (CS) for 1 hour once daily for 4 days before induction of IBD by 2,4, 6-trinitrobenzene sulfonic acid (TNBS)-ethanol enema and were then killed at 2, 6, or 24 hours later. RESULTS: Preexposure to CS significantly potentiated colonic damage induced by TNBS. TNBS-ethanol enema caused a pronounced increase in colonic myeloperoxidase activity, leukotriene B(4) level, and also inducible nitric oxide synthase activity, its protein, and messenger RNA expression. These parameters were all significantly increased further by exposure to CS. In contrast, increased colonic superoxide dismutase activity after TNBS-ethanol enema was attenuated by CS exposure. The potentiating effects of CS exposure on TNBS-induced IBD were significantly alleviated after pretreatment with cyclosporin A (an immunosuppressant), N (G)-nitro-L-arginine methylester (a nitric oxide synthase inhibitor), and dimethyl sulfoxide (a hydroxyl radical scavenger). CONCLUSIONS: The results show that promotion of neutrophil infiltration and free radical production contributed significantly to the potentiating effect of passive cigarette smoking on experimental IBD.
Animals↗
The correlation of the weakening effect on gastric mucosal integrity by 5-HT with neutrophil activation.
The effects of 5-hydroxytryptamine (5-HT) on ethanol-induced gastric mucosal damage and on epithelial and vascular integrity were investigated. Male Sprague-Dawley rats were administered with 5-HT (5 or 10 mg/kg, IP) 30 min prior to the challenge with ethanol (40% v/v, 10 ml/kg, PO). 5-HT dose dependently aggravated ethanol-induced injury in the gastric mucosa. Both xanthine oxidase (XO) and myeloperoxidase (MPO) activities in the mucosa were significantly increased with the high dose of 5-HT, which also potentiated the elevation of these enzyme activities by ethanol. However, the mucosal superoxide dismutase activity was left unaltered. In neutropenic (antineutrophil serum-treated) animals, the ethanol-induced gastric mucosal injury was significantly ameliorated, with or without the pretreatment of 5-HT (10 mg/kg). In addition, the effect of 5-HT on the activity of MPO, but not of XO, was also attenuated in these animals. In the ex vivo gastric chamber study on pentobarbital-anesthetized animals, volume of gastric secretion was significantly decreased in the 5-HT-treated groups, with further reduction after ethanol incubation. Transmucosal potential difference (PD) was significantly reduced in 5-HT-treated rats, which also potentiated the ethanol-induced drop in PD. Nevertheless, 5-HT dose dependently increased mucosal vascular permeability and further enhanced during ethanol incubation. These findings suggest that 5-HT adversely affects the defense mechanisms of the gastric mucosa by reducing the secretory function of the mucosal cells and to weaken the epithelial and vascular integrity. Neutrophil activation appears to be responsible for the detrimental effects of 5-HT partly through the elevation in MPO activity. The increase in mucosal XO activity by 5-HT may induce free radical production and possibly modulate the ulcerogenic processes.
Animals↗
Histological study of mechanisms of adaptive cytoprotection on ethanol-induced mucosal damage in rat stomachs.
Adaptive cytoprotection in the gastric mucosa could be induced by exposure to low concentrations of noxious agents. However, experimental results reported so far were based on macroscopic studies. We aimed to investigate the phenomenon of gastric adaptive cytoprotection of mild irritants and its correlation with intramucosal mucus at the histological level. It was found that histological damage induced by ethanol had a negative correlation with the length of the mucus-secreting layer in the gastric mucosa. Mild irritants such as 20% ethanol and 5% NaCl preserved the 100% ethanol-induced intramucosal mucus depletion, but only the former agent demonstrated a cytoprotective effect against the histological damage, indicating that preservation of intramucosal mucus may not necessarily play a permissive role in adaptive cytoprotection. The capsaicin-sensitive sensory afferent neurons, sensory chemoreceptors, muscarinic receptors, alpha2-adrenoceptors and peripheral dopamine D2-receptors were found to be the components of the autonomic nervous system involved in the cytoprotective processes of 20% ethanol. Endogenous mediators including nitric oxide, prostaglandins, and possibly nonprotein sulfhydryl compounds also seemed to participate in such protection. Nevertheless, 0.3 M HCl did not show any effect either on mucosal damage or depletion of intramucosal mucus induced by absolute ethanol. These findings suggest that only 20% ethanol shows histological cytoprotection, which would involve various components of the autonomic nervous system and endogenous mediators. Furthermore, this investigation also implies a new perspective: that in order to study a true adaptive cytoprotection, histological examination of the gastric mucosa should be performed.
Adaptation, Physiological↗
MR imaging of non-visualized pulmonary arteries at angiography in patients with congenital heart disease.
The aim of this study was to evaluate whether MR could depict pulmonary arterial anatomy in more detail than routine angiography in patients with congenital interruption or acquired occlusion of the left pulmonary artery or pulmonary atresia. This study included 10 patients with tetralogy of Fallot (n=6) or pulmonary atresia with ventricular septal defect (n=3) or aorticopulmonary window (n=1) diagnosed by cardiac angiography and MR. Surgical confirmation was made in seven patients. Interruption of the proximal left pulmonary artery, diagnosed at the time of evaluation, was found in seven patients and acquired obstruction of the hilar pulmonary artery (PA) was found in two at cardiac angiography. In the remaining one patient with pulmonary atresia and an occluded palliative shunt, the central PA was not visualized at angiography. MR showed 3-6 mm-sized hilar PAs in five and a central PA in a patient with pulmonary atresia. In 4 of 6 (67%) surgically-proven patients with congenital or acquired left PA obstruction, the status of the PA distal to the obstruction was correctly diagnosed with MR. In conclusion, MR is an effective modality in depicting sizable PAs when routine angiography fails to visualize the PA anatomy.
Adolescent↗
Two cases of atrial flutter with fetal hydrops: successful fetal drug therapy.
We describe two cases of fetal atrial flutter associated with severe fetal hydrops which were unresponsive to digoxin but were successfully treated with flecainide acetate. Two cases of fetal atrial flutter were identified in fetuses with severe fetal hydrops on 3rd trimester ultrasonogram(28 weeks' gestation and 30 weeks' gestation). Following failed digoxin monotherapy, flecainide acetate was added to digoxin. On the 7th day and 13th day after combined therapy, fetal heart rate converted to normal sinus rhythm without recurrence. Our cases showed that the combined therapy of digoxin and flecainide acetate can effectively treat fetal atrial flutter associated with fetal hydrops unresponsive to digoxin monotherapy.
Adult↗
Cell cycle regulators during human atrial development.
OBJECTIVES: The molecular mechanisms that regulate cardiomyocyte cell cycle and terminal differentiation in humans remain largely unknown. To determine which cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) are important for cardiomyocyte proliferation, we have examined protein levels of cyclins, CDKs and CKIs during normal atrial development in humans. METHODS: Atrial tissues were obtained in the fetus from inevitable abortion and in the adult during surgery. Cyclin and CDK proteins were determined by Western blot analysis. CDK activities were determined by phosphorylation amount using specific substrate. RESULTS: Most cyclins and CDKs were high during the fetal period and their levels decreased at different rates during the adult period. While the protein levels of cyclin D1, cyclin D3, CDK4, CDK6 and CDK2 were still detectable in adult atria, the protein levels of cyclin E, cyclin A, cyclin B, cdc2 and PCNA were not detectable. Interestingly, p27KIP1 protein increased markedly in the adult period, while p21CIP1 protein in atria was detectable only in the fetal period. While the activities of CDK6, CDK2 and cdc2 decreased markedly, the activity of CDK4 did not change from the fetal period to the adult period. CONCLUSION: These findings indicate that marked reduction of protein levels and activities of cyclins and CDKs, and marked induction of p27KIP1 in atria, are associated with the withdrawal of cardiac cell cycle in adult humans.
Adult↗
Rare variants of divided right ventricle with sequestered apical trabecular component.
The right ventricle may be divided into two or more compartments by various structures in various ways. Rarely, the apical trabecular component may be sequestered from the rest of the right ventricle. We report 4 cases with different underlying lesions that share a common pathology of apical sequestration of the right ventricle resulting in diverse hemodynamic consequences. Case 1 had pulmonary valve stenosis. The apical sequestration of the right ventricle resulted in no significant hemodynamic consequence. Case 2 had multiple defects in the muscular ventricular septum. The volume of left-to-right shunt seemed to be reduced because of the commitment of some of the defects to the sequestered cavity. Case 3 had a large defect in the trabecular septum. As the defect involved the whole septum that was related to the sequestered right ventricular apex, the left ventricle together with the sequestered right ventricle formed a boot-shaped chamber. Hemodynamically, the muscular shelf was an interventricular septum. Case 4 had a coronary artery fistula to an isolated cavity that occupied the apical region of the right ventricle. The pathology was similar to the case that was reported as a five-chambered heart. The abnormal cavity was, in fact, the sequestered right ventricular apex.
Adolescent↗