Background  Gene and stem cell therapies hold promise for the treatment of ischaemic cardiovascular disease. However, combined stem cell and angiogenic growth factor gene therapy for acute ischaemic myocardium has not been previously reported. This study hypothesized that combined stem cell and gene therapy would not only augment new vessels formation but also improve myocardial function in acute ischaemic myocardium.

Objectives: Myostatin, a negative regulator of muscle growth, is increased in hypertrophied and infarcted heart. However, the mechanism of regulation is not known. Mechanical stress is an important regulatory factor for cardiomyocyte growth. The aim of the study was to investigate the effect of cyclic stretch on the expression of myostatin gene in cardiomyocytes.Methods: Neonatal Wistar rat cardiomyocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation at 60 cycles/min. An in vivo model of aorta-caval shunt in adult rats was used to investigate the myostatin expression.Results: Cyclic stretch significantly increased myostatin protein and mRNA expression after 6 to 18 11 of stretch. Addition of the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580, insulin-like growth factor-1 (IGF-1) monoclonal antibody, and p38 siRNA 30 min before stretch inhibited the induction of myostatin protein. Cyclic stretch increased, while SB203580, IGF-1, and 1GF-1 receptor antibody abolished, the phosphorylated p38 protein. Gel shift assays showed significant increase of DNA-protein binding activity of myocyte enhancer factor 2 (MEF2) after stretch, and transfection with p38 siRNA abolished the DNA-protein binding activity induced by cyclic stretch. Cyclic stretch significantly increased the IGF-1 secretion from myocytes. Both conditioned media from stretched myocytes and exogenous administration of IGF-1 recombinant protein to the non-stretched myocytes increased myostatin protein expression similar to that seen after cyclic stretch. An in vivo model of aorta-caval shunt in adult rats also demonstrated the increased myostatin expression in the myocardium.Conclusions: Cyclic mechanical stretch enhances myostatin expression in cultured rat neonatal cardiomyocytes. The stretch-induced myostatin is mediated by IGF-1 at least in part through a p38 MAP kinase and MEF2 pathway. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

BACKGROUND:The use of beta-blockers has emerged as a beneficial treatment for congestive heart failure. Hypoxia-inducible factor-1alpha (HIF-1alpha) is tightly regulated in the ventricular myocardium. However, the expression of HIF-1alpha in chronic heart failure resulting from volume overload and after treatment with beta-blocker is little known.METHODS AND RESULTS:To test the hypothesis that HIF-1alpha plays a role in the failing myocardium because of volume overload, an aorta-caval shunt was created for 4 weeks in adult Sprague-Dawley rats to induce volume-overload heart failure. Carvedilol at 50 mg/kg body weight per day after surgery was given. The heart weight and body weight ratio increased from 2.6 +/- 0.3 in the sham group to 3.9 +/- 0.7 (P < .001) in the shunt group. Left ventricular end-diastolic dimension increased from 6.5 +/- 0.5 mm to 8.7 +/- 0.6 mm (P < .001). Treatment with carvedilol in the shunt group reversed the heart weight and ventricular dimension to the baseline values. Western blot showed that HIF-1alpha, vascular endothelial growth factor (VEGF), and brain natriuretic peptide (BNP) proteins were upregulated and nerve growth factor-beta (NGF-beta) downregulated in the shunt group. Real-time polymerase chain reaction showed that mRNA of HIF-1alpha, VEGF, and BNP increased and mRNA of NGF-beta decreased in the shunt group. Treatment with carvedilol reversed both protein and mRNA of HIF-1alpha, VEGF, BNP, and NGF-beta to the baseline values. Increased immunohistochemical labeling of HIF-1alpha, VEGF, and BNP in the ventricular myocardium was observed in the shunt group and carvedilol again normalized the labeling.CONCLUSION:HIF-1alpha and VEGF mRNA and protein expression were upregulated in the rat model of volume-overload heart failure. Treatment with carvedilol is associated with a reversal of abnormal regulation of HIF-1alpha and VEGF in the failing ventricular myocardium.

BACKGROUND AND PURPOSE Mechanical forces have profound effects on vascular smooth muscle cells (VSMCs). The mechanism by which mechanical stimuli regulate vascular endothelial growth factor (VEGF) expression and regulation has yet to be elucidated. We investigated the effect of cyclical mechanical stretching on regulation of the VEGF gene in VSMCs. MATERIALS AND METHODS Cultured rat VSMCs grown on a flexible membrane base were stretched by applying a vacuum at 60 cycles/minute. VEGF concentration in the cultured media was determined by enzyme-linked immunoassay. VEGF gene expression was determined by Western blot and Northern blot. The location of VEGF in the VSMC was studied immunohistochemically. Chimeric constructs of the VEGF promoter were deleted and the promoter activity was determined by luciferase activity. RESULTS VEGF concentration increased by 21 to 32% as early as 10 minutes after stretching and remained at this level for up to 12 hours. The concentration of VEGF reached a maximum of 2.8-fold over that in control cells by 2 hours after stretching and declined slightly thereafter. The amount of VEGF mRNA in stretched cells increased as early as 1 hour after stretching, reached a maximum of 3.2-fold over the amount in control cells by 2 hours, and remained at this level for up to 6 hours after stretching. Immunohistochemical study confirmed increased VEGF expression in VSMCs after stretching. Stretched cells transfected with a Sac-Nhe fragment showed only 46% of the luciferase activity of unstretched control cells. However, stretched cells transfected with chimeric plasmids containing a Spe-Nhe fragment showed 2.8-fold luciferase activity over that in control cells. CONCLUSIONS Cyclical mechanical stretching upregulates expression of the VEGF gene in VSMCs at the transcription level. The VEGF 5'-flanking region contains a negative stretch-response element located in the 0.4-kb Sac-Pst fragment and a positive stretch-response element located in the 0.6-kb Spe-Sac fragment.

Left main coronary artery (LMCA) disease is now uniformly treated with coronary artery bypass grafting (CABG). However, some patients with LMCA disease do not receive CABG because of high operative risks. The advent of stent implantation has permitted a non-operative improvement in myocardial blood flow in many patients with single- and multi-vessel coronary artery disease. However, the outcomes of stent implantation for unprotected LMCA disease are still unclear. Stent implantation was performed for unprotected LMCA disease in 13 patients; eight patients had high operative risk and five patients had refused CABG. The primary success rate was 100% (13/13 patients). One patient (8%) developed a non-Q-wave myocardial infarction after LMCA stenting. Repeat angiography was obtained in five patients (38%) with recurrent angina, and three patients (23%) received repeated percutaneous transluminal coronary angioplasty (PTCA) for LMCA restenosis. In the follow-up period of 18+/-3 months, 12 patients (92%) remained in satisfactory condition with no further need for surgical intervention. One patient (8%) ultimately required CABG, and she died after CABG at 3 months after LMCA stenting. In conclusion, although CABG remains the standard treatment for LMCA disease, the present study demonstrates that stent implantation is a safe and clinically beneficial revascularization procedure for unprotected LMCA disease in patients who have high operative risk as well as those who refuse CABG.

Twenty probe-holes were driven into Pit 9 by the OU 7-10 Staged Interim Action Project during November and December 1999. Active and passive neutron and gamma measurements were made during January and February 2000 using neutron gamma logging tools. The results of this logging were provided to the Project by Waste Management Technical Services (WMTS) of Richland, WA in April 2000. The apparent low soil moisture content in the waste zone triggered an evaluation of the significance of those readings. This report presents that evaluation along with the results of the findings and recommendations for future work.

BACKGROUND:Regional differences in recovery of tachycardia-induced changes of atrial electrophysiological properties have not been well studied.METHODS AND RESULTS:In the control group (5 dogs), atrial effective refractory period (AERP) and inducibility of atrial fibrillation (AF) were assessed before and every 4 hours for 48 hours after complete atrioventricular junction (AVJ) ablation with 8-week VVI pacing. In experimental group 1 (15 dogs), AERP and inducibility of AF were assessed before and after complete AVJ ablation with 8-week rapid right atrial (RA) pacing (780 bpm) and VVI pacing. In experimental group 2 (7 dogs), AERP and inducibility of AF were assessed before and after 8-week rapid left atrial (LA) pacing and VVI pacing. AERP and inducibility and duration of AF were obtained from 7 epicardial sites. In the control group, atrial electrophysiological properties obtained immediately and during 48-hour measurements after pacing did not show any change. In the 2 experimental groups, recovery of atrial electrophysiological properties included a progressive recovery of AERP shortening, recovery of AERP maladaptation, and decrease of duration and episodes of reinduced AF. However, recovery of shortening and maladaptation of AERP and inducibility of AF was slower at the LA than at the RA and Bachmann's bundle.CONCLUSIONS:The LA had a slower recovery of tachycardia-induced changes of atrial electrophysiological properties, and this might play a critical role in initiation of AF.

BACKGROUNDVarious clinical manifestations of cardiovascular diseases have a pattern of circadian variation. In this study, we investigated whether the onset and duration of paroxysmal supraventricular tachycardia (PSVT) has a circadian variation.METHODS AND RESULTSIn our analysis, we included 105 patients with 498 PSVT episodes. In this study, the onset of PSVT did not have a uniform distribution throughout the 24-h period. There were nearly equal peaks in the time periods from 8:00 to 9:00 AM, 12:00 to 1:00 PM, and 5:00 to 6:00 PM, with a trough at night. The duration of PSVT also did not show a uniform distribution throughout the 24-h period; it increased significantly during the daytime, with a peak between 1:00 and 2:00 PM, another peak between 6:00 and 7:00 PM, and a significant reduction at night.CONCLUSIONSThe onset and duration of PSVT showed a circadian variation. However, the time-oriented antiarrhythmic therapy for preventing PSVT needs further study.

Atrial fibrillation (AF) is a common arrhythmia after coronary artery bypass surgery (CABG). The purpose of this study was to determine the role of P wave duration, amplitude and dispersion in the prediction of AF after CABG. This study included 120 patients undergoing elective CABG. Clinical characteristics, 12-lead electrocardiogram (ECG), echocardiogram and coronary angiogram were obtained in all patients. We measured P wave duration, amplitude and dispersion from 12-lead ECG in each patient. After CABG, all patients were continuously monitored for AF attacks in the intensive care unit and ordinary ward. Our results showed that age greater than 60 years was the strongest predictor of postoperative AF (p<0.01), with a 3.7-fold greater likelihood of developing postoperative AF compared to ages less than 60 years. Gender was another independent predictor of postoperative AF, with men being 3.0 times more likely to develop postoperative AF compared to women (p=0.03). The presence of prolonged P wave duration (≥100 ms in lead II) was also an independent predictor (p=0.04), with 2.9-fold greater risk of developing postoperative AF compared to a P wave duration of less than 100 ms. The P wave dispersion was similar between patients with and without postoperative AF (29±15 vs. 33±15 mm, p=NS). In conclusion, old age, male gender and prolonged P wave duration were independent predictors of AF after CABG. However, P wave dispersion and amplitude did not provide significant information in the prediction of postoperative AF.

We present here, the case of a 22-year-old male suffering from persistent tachycardia for the past 3 years. His resting pulse rate was rarely below 100 beats/min, and it frequently increased to as high as 150 beats/min even after a minimal of activity. Associated symptoms included palpitation, chest tightness, dyspnea and presyncope, either during rest or with exercise. Propranolol and verapamil could not control the tachycardia. The application of radiofrequency energy to an area in the superior right atrium that demonstrated a discrete electrogram with earliest endocardial activation during tachycardia resulted in a decrease in sinus rate from 120 beats/min to 70 beats/min. Follow-up on Holter monitor, performed one month later, demonstrated an average heart rate of 84 beats/min (range 60-125). In exercise tolerance test, the patient exercised for 9 minutes, achieving a maximum heart rate of 140 beats/min. This patient remained asymptomatic without any antiarrhythmic drug during the 3-month follow-up period. Medical management in case of patients showing disabling inappropriate sinus tachycardia refractory, sinus node modification could be considered as an suitable alternative to complete atrioventricular junctional ablation.

Recent genotype-phenotype correlation studies in familial hypertrophic cardiomyopathy (FHC) have revealed that some mutations in the beta- myosin heavy chain (BMHC) gene may be associated with a high incidence of sudden death and a poor prognosis. Coexistence of sudden death and end-stage heart failure in several families with FHC has recently being reported; however, the genetic basis of such families has not been clearly demonstrated. A three-generation Chinese familial hypertrophic cardiomyopathy (FHC) family (family HLI) with two cases of end-stage heart failure and three cases of sudden death was analyzed. The average age of death in the affected members in this family was 34 years old. Genetic linkage analysis using polymorphisms in the (alpha- and beta-myosin heavy chain genes revealed that FHC in this family is significantly linked to the BMHC gene without recombinations. Single-strand conformation polymorphism analysis of exons 8, 9 and 13 to 23 in the BMHC gene showed a polymorphic band on exon 14 that is in complete linkage with the disease status in this family. DNA sequencing analysis in the affected members revealed an 453Arg-->Cys mutation in the BMHC gene. To our knowledge this is the first reported mutation of FHC in Chinese. Our data suggest that the 453Arg-->Cys mutation is associated with a malignant clinical course in FHC due not only to sudden death but also to end-stage heart failure.

Apical segmental dysfunction is an unusual finding in hypertrophic cardiomyopathy (HCM). It is characterized by a poor clinical course and a high incidence of malignant ventricular tachyarrhythmias. Long-term prognosis of patients with HCM and apical segmental dysfunction is still unclear. We report 2 cases of apical segmental dysfunction in HCM in whom progressive apical dilatation and congestive heart failure developed. Both patients died suddenly, and intractable ventricular tachyarrhythmias were documented in 1 case during resuscitation. This report provides further evidence that apical segmental dysfunction might predict a subgroup of patients with HCM who are likely to develop end-stage heart failure and are at high risk of sudden cardiac death.

This report evaluates both the positive and negative consequences of adding water to a degraded reactor core during a severe accident. The evaluation discusses the earliest possible stage at which an accident can be terminated and how plant personnel can best respond to undesired results. Specifically discussed are (a) the potential for plant personnel to add water for a range of severe accidents, (b) the time available for plant personnel to act, (c) possible plant responses to water added during the various stages of core degradation, (d) plant instrumentation available to understand the core condition and (e) the expected response of the instrumentation during the various stages of severe accidents.

The mechanisms leading to formation of spontaneous echo contrast (SEC), a smoke-like echo on echocardiography, are still controversial. To further explore the clinical implications and factors related to SEC formation, the correlation among echocardiographic variables, hematologic parameters or platelet aggregability, and the occurrence of SEC was studied in 119 patients with chronic nonvalvular atrial fibrillation. There were 75 men and 44 women with a mean age of 65 +/- 10 years (range 38-88). Left atrial SEC was detected in 39 patients (33%) by transesophageal echocardiography. Patients with history of systemic embolism were more frequently found to have left atrial SEC and left atrial thrombus by univariate analysis. Multivariate analysis showed that left atrial SEC (p < 0.001) was the only independent predictor of history of systemic embolism. Age, sex, left atrial or left ventricular dimension, left ventricular ejection fraction, antiplatelet or anticoagulant therapy and the percentage of lone atrial fibrillation were not significantly different between patients with and without left atrial SEC. Among the hematologic parameters, higher hematocrit was found in patients with left atrial SEC, while white blood cell and platelet counts were comparable in both groups. Platelet aggregability with different concentrations of inducers, adenosine diphosphate and collagen, was evaluated by the turbidimetric method in 15 patients with left atrial SEC and in 42 patients without left atrial SEC who were not receiving antiplatelet or anticoagulant therapy. No significant difference was found in platelet aggregability using four inducer concentrations between two groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Left atrial thrombi have been considered to be the major source of systemic arterial embolization in patients with rheumatic mitral valve disease. Almost half of the left atrial thrombi are found in the left atrial appendage (LAA). To investigate LAA size and LAA contractile function in patients with rheumatic mitral valve disease, transesophageal echocardiographic and Doppler studies were performed in 61 patients. Among them, 46 patients were in atrial fibrillation (group 1), while the other 15 were in sinus rhythm (group 2). Thirty-six patients with nonrheumatic atrial fibrillation were chosen as control to group 1. Another 22 patients with various cardiovascular diseases and sinus rhythm served as control to group 2. When compared to the patients with nonrheumatic atrial fibrillation (control group), group 1 patients tended to have a larger LAA maximal area (9.7 +/- 5.2 vs. 5.9 +/- 2.8 cm2; p < 0.001). LAA ejection fraction and LAA peak emptying velocity were also lower. A significantly higher incidence of LAA spontaneous echo contrast (SEC) and thrombus formation was also found in these patients. Group 2 patients were also found to have a larger LAA maximal area when compared to the control group (8.8 +/- 3.7 vs. 5.2 +/- 3.0 cm2; p < 0.001). LAA ejection fraction and LAA peak emptying velocity were lower in this group, too. A higher incidence of LAA SEC formation was found in these patients with rheumatic mitral valve disease (4/15 vs. 0/22; p = 0.021). There was no significant difference, however, in LAA thrombus formation between group 2 and its control group (1/15 vs. 1/22; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

This study evaluated the relation between left atrial appendage (LAA) function and LAA spontaneous echo contrast (SEC) or thrombus formation. Seventy-five patients (45 men and 30 women, aged 14-79 years) referred for transesophageal echocardiography (TEE) were examined for LAA area (maximal and minimal), LAA ejection fraction ([LAA maximal area--LAA minimal area]/LAA maximal area), LAA peak emptying velocity, and these patients were classified into three groups by different LAA blood flow patterns: Group 1--25 patients with well-defined biphasic configuration of LAA flow; Group 2--28 patients with multiphasic configuration of LAA flow; Group 3--22 patients with very low LAA blood flow and, sometimes, barely detected Doppler signal. All the 25 patients in Group 1 had a sinus rhythm during TEE study, while the other 50 patients in Groups 2 and 3 were in atrial fibrillation. The patients in Group 3 had the lowest LAA ejection fraction and the lowest peak emptying velocity of these three groups. LAA SEC was present in five of 28 patients in Group 2 and 14 of 22 patients in Group 3, but in none of 25 patients in Group 1 (P < 0.001). LAA thrombus was present in one of 25 patients in Group 1, two of 28 patients in Group 2, and seven of 22 patients in Group 3 (P < 0.05). In conclusion, this study found that patients with poor LAA function, which was represented by lower LAA ejection fraction and lower peak emptying velocity, had higher incidence of LAA SEC or thrombus formation.

The presence of a left atrial thrombus is considered to be a relative contraindication to percutaneous transvenous mitral commissurotomy (PTMC) in patients with rheumatic mitral stenosis. However, resolution of left atrial thrombus after anticoagulant therapy with warfarin makes PTMC possible. From July 1989 to June 1991, a total of 70 patients with rheumatic mitral stenosis received PTMC at National Taiwan University Hospital. Of these, four patients underwent PTMC uneventfully after resolution of left atrial thrombi with anticoagulant therapy. The prothrombin time was kept at around 1.5 times that for the normal controls and transesophageal echocardiography (TEE) was used for follow-up. The time for resolution of left atrial thrombi was 1.5, 11, 12, and 2 months. In all four patients with chronic atrial fibrillation, TEE revealed the presence of left atrial thrombi; in only two of these cases was there a suspicion of left atrial thrombi on transthoracic echocardiography. It is concluded that: (1) left atrial thrombi may be resolved after anticoagulant therapy with warfarin, but the time required varies for different patients; and (2) TEE is better than conventional transthoracic echocardiography for detecting a left atrial thrombus and is recommended as the tool of choice for observing the response of a left atrial thrombus to anticoagulant therapy.

Neutronics evaluations show that fuel recycled by the atomic international reduction and oxidation. (AIROX) method has comparable neutronics performance over an extended fuel cycle. In this paper, results of ORIGEN2 calculations to determine the decay heat and radioisotope loadings of AIROX-recycled fuel are presented. In the AIROX process, the spent fuel is oxidized from UO[sub 2] to U[sub 3]O[sub 8] by oxygen and then reduced back to UO[sub 2] by hydrogen. The process reduces the fuel to a fine powder to which fissile uranium or plutonium can be added to make new fuel. In the process, some volatile fission products are liberated from the spent fuel, but the actinides are retained.

The presence of a valve ring abscess in patients with infective endocarditis adds appreciably to the expected rates of morbidity and mortality. From January 1989 to October 1991, a total of 43 consecutive patients with infective endocarditis seen at National Taiwan University Hospital were enrolled in this study. There were 30 men and 13 women, ranging in age from 14 to 75 years (mean +/- SD 38.5 +/- 15.0 years). The presence of infective endocarditis was documented by surgery in 26 patients and was based on a clinical diagnosis in the remaining 17 patients. A valve ring abscess was detected in five patients, either by transthoracic or transesophageal echocardiography, and all were confirmed at surgery. Aortic valve endocarditis was more frequently found in patients with valve ring abscesses (100% vs 31.6%, p < 0.01), and the infecting organism was most often Staphylococcus aureus (60.0% vs 15.8%, p < 0.05). The proportion of urgent operations was also higher in the group with abscesses (80.0% vs 23.7%, p < 0.05). The hospital mortality was 40.0% in patients with abscesses and 5.3% in patients without abscesses, but the difference did not reach significance (p = 0.056). Transthoracic echocardiography identified valve ring abscesses in the first three patients, but transesophageal echocardiography was more useful in detecting abscesses located in the posterior aspect of the aortic root in the other two patients, in which the lesion was overlooked or only suspected by the transthoracic approach.(ABSTRACT TRUNCATED AT 250 WORDS)