Reduction of blood pressure elevation by losartan in spontaneously hypertensive rats through suppression of LARG expression in vascular smooth muscle cells.

BACKGROUND/PURPOSE: This study sought to elucidate the mechanism by which losartan inhibits blood pressure (BP) elevation in spontaneously hypertensive rats (SHRs). METHODS: Four-week-old Wistar-Kyoto (WKY) rats and SHRs were either treated with losartan (20 mg/kg/day) for 8 weeks or served as untreated controls. BP was measured by the tail-cuff method. At 12 weeks, isometric contraction of the aortic rings of the rats was evaluated with a force transducer and recorder. The mRNA and protein levels of the target Rho guanine nucleotide exchange factors (RhoGEFs), and the extent of myosin phosphatase target subunit 1 (MYPT-1) phosphorylation in the aorta, were determined using quantitative real-time polymerase chain reaction (qPCR) assay and Western blot analysis. RESULTS: The BP of the four-week-old SHRs did not differ from that of the age-matched WKY rats, whereas the BP of the twelve-week-old control group SHRs was higher than that of the control group WKY rats. Losartan treatment, however, inhibited BP elevation in both rat strains, doing so to a greater extent in the treatment group SHRs. The contractile force in response to angiotensin II of the aortic rings from the SHRs treated with losartan was significantly lower than that of the aortic rings from the non-treated SHRs. The protein expression of leukemia-associated RhoGEF (LARG) was significantly higher in the non-treated SHRs compared to the non-treated WKY rats. CONCLUSION: The study results showed that the reduction of BP elevation by losartan in SHRs occurs through the suppression of LARG expression and MYPT-1 phosphorylation in vascular smooth muscle cells.

Coronary Artery Complications in Pediatric Patients with Kawasaki Disease: A 12-Year National Survey.

BACKGROUND: Coronary artery complications are the predominant causes of morbidity and mortality in childhood Kawasaki disease (KD). The aim of this study was to investigate the incidence of coronary artery complications and cardiac sequelae in pediatric patients with KD. METHODS: Using the Taiwan National Health Insurance (NHI) database from 1997 to 2008, records of patients with KD were reviewed retrospectively, utilizing the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 446.1 in pediatric patients aged 18 years or under. The ICD-9CM was also used to identify the outcomes for coronary artery complications (ICD-9-CM codes 410-414), including coronary artery aneurysm (CAA) (ICD-9-CM code 414.11). RESULTS: From the records of pediatric patients with KD admitted to hospitals between 1997 and 2004, 8148 patients without any history of coronary artery complications before KD were selected for study. Of those patients, 694 patients (8.5%) were followed-up until the end of 2008 to estimate the incidence of coronary artery complications. The ratio of boys to girls with coronary artery complications was 1.84, and the incidence of coronary artery complications was 11.53 per 1,000 person-years. Among the 8148 pediatric patients with KD, 12 patients (0.15%; 8 boys and 4 girls) had myocardial infarction, and 20 patients (0.25%; 12 boys and 8 girls) died during follow-up. CONCLUSIONS: This study is the first report regarding the incidence of coronary artery complications in KD children aged 18 years or younger. The incidence of coronary artery complications was higher as patients progressed in age, and increased by year. However, major complications such as death and myocardial infarction did not frequently occur. KEY WORDS: Cardiac sequelae; Coronary artery complications; Incidence; Kawasaki disease.

Differential baseline expression and angiotensin II-stimulation of leukemia-associated RhoGEF in vascular smooth muscle cells of spontaneously hypertensive rats.

PURPOSE: Studies to explore angiotensin II (Ang II) and its downstream signaling pathways via Rho guanine nucleotide exchange factors (RhoGEFs) and RhoA signaling are crucial to understanding the mechanisms of smooth muscle contraction leading to hypertension. This study aimed to investigate the Ang II-induced expression of RhoGEFs in vascular smooth muscle cells (VSMCs) of spontaneously hypertensive rats (SHRs) and to identify the possible regulator associated with hypertension. METHODS: Cultured VSMCs of the aorta from SHRs and Wistar-Kyoto (WKY) rats were treated with or without Ang II or Ang II plus Ang II type 2 receptor antagonists. The expression levels of RhoGEF messenger RNA (mRNA) and protein were determined. To evaluate the changes of aortic ring contractile force in response to Ang II, a nonviral carrier system was adopted to deliver the leukemia-associated RhoGEF (LARG) small interfering RNA via nanoparticles into aortic rings. RESULTS: The baseline mRNA levels of three RhoGEFs in cultured VSMCs of WKY rats did not increase with age, but they were significantly higher in 12-week-old SHRs than in 5-week-old SHRs. Expression levels of LARG mRNA were higher in SHRs than in age-matched WKY rats. The baseline LAGR protein of 12-week-old SHRs was about four times higher than that of WKY rats of the same age. After Ang II-stimulation, LAGR protein expression was significantly increased in 12-week-old WKY rats but remained unchanged in 12-week-old SHRs. LARG small interfering RNA was successfully delivered into aortic rings using nanoparticles. LARG knockdown resulted in 12-week-old SHRs showing the greatest reduction in aortic ring contraction. CONCLUSION: There were differences in age-related RhoGEF expression at baseline and in response to Ang II-stimulation between SHRs and WKY rats in this study. Nanotechnology can assist in studying the silencing of LARG in tissue culture. The findings of this study indicate that LARG gene expression may be associated with the genesis of hypertension in SHRs.

Angiotensin II regulates the LARG/RhoA/MYPT1 axis in rat vascular smooth muscle in vitro.

AIM: To identify a key protein that binds monomeric G protein RhoA and activates the RhoA/Rho kinase/MYPT1 axis in vascular smooth muscle cells (VSMCs) upon angiotensin II (Ang II) stimulation. METHODS: Primary cultured VSMCs from Sprague-Dawley rats were transfected with siRNAs against leukemia-associated RhoGEF (LARG), and then treated with Ang II, losartan, PD123319, or Val(5)-Ang II. The target mRNA and protein levels were determined using qPCR and Western blot analysis, respectively. Rat aortic rings were isolated, and the isometric contraction was measured with a force transducer and recorder. RESULTS: Stimulation with Ang II (0.1 µmol/L) for 0.5 h significantly increased the level of LARG mRNA in VSMCs. At 3, 6, and 9 h after the treatment with Ang II (0.1 µmol/L) plus AT(2) antagonist PD123319 (1 µmol/L) or with AT(1) agonist Val(5)-Ang II (1 µmol/L), the LARG protein, RhoA activity, and phosphorylation level of myosin phosphatase target subunit 1 (MYPT1) in VSMCs were significantly increased. Knockdown of LARG with siRNA reduced these effects caused by AT(1) receptor activation. In rat aortic rings pretreated with LARG siRNA, Ang II-induced contraction was diminished. CONCLUSION: Ang II upregulates LARG gene expression and activates the LARG/RhoA/MYPT1 axis via AT(1), thereby maintaining vascular tone.

Brugada-type electrocardiogram in the Taiwanese population--is it a risk factor for sudden death?

BACKGROUND/PURPOSE: People receive electrocardiogram (ECG) examination for various reasons in a hospital setting. An important clinical practice issue may be that cardiologists need to be consulted for Brugada-type ECGs identified through routine screening. We investigated the prevalence and prognosis of patients with Brugada-type ECG in a hospital-based population in an attempt to improve the management of these patients. METHODS: In 20,562 patients seeking medical care for non-cardiovascular reasons, 74,955 ECGs were performed from December 1999 to February 2001. The diagnostic criteria for Brugada-like ECG from the European Society of Cardiology were used. International Statistical Classification of Diseases codes and city residents' records were documented to indicate the reasons for visiting clinics or hospitalization and mortality outcome. Medical records were reviewed and telephone interviews were conducted. RESULTS: Twenty-six (0.13%) of the 20,562 patients were confirmed to have Brugada-type ECGs. None of these patients had ever experienced syncope, near syncope or sudden cardiac death. After 57.1 ± 15.8 months of follow-up, there were four deaths out of the 26 patients with Brugada-type ECG (15.4%, 95% CI: 1.53-2.9%) compared with 2899 of those without (14.1%, 95% CI: 13.6-14.5%; p=0.89, log-rank test). Neither sudden cardiac death (p=0.61) nor hospitalized death (p=0.55) was different between patients with and without Brugada-type ECG. CONCLUSION: Patients with Brugada-type ECGs are not rare in a hospital-based population. The presence of Brugada-type ECGs in patients without syncope or sudden cardiac death was not associated with hospitalized mortality.

Enhanced activity and subcellular redistribution of myocardial hexokinase after acute myocardial infarction.

BACKGROUND: Hexokinase (HK) is known to possess both anti-oxidant and anti-apoptotic properties. This study investigated the behavior of myocardial HK in response to myocardial infarction (MI). METHODS: Adult male Wistar rats with various degrees of MI after coronary ligation were examined 4 weeks after operation and were divided dichotomously into small and large MI groups. The activity and subcellular distribution of HK in the non-infarcted myocardium were determined. In parallel, myocardial oxidative stress determined using aconitase activity and malondialdehyde content, and left ventricular function using echocardiography were studied. RESULTS: In the mitochondria and the cytosol, HK activity was enhanced after MI and paralleled the increases in oxidative stress and left ventricular end-diastolic dimension (LVEDD). The enhancement in HK activity varied between subcellular compartments and resulted in an increase in the ratio of cytosol to whole-cell HK activity, which was proportional to oxidative stress and LVEDD. CONCLUSIONS: The activities of HK in all subcellular fractions are enhanced in response to MI. However, enhanced proportion of cytosolic HK relative to whole-cell HK activity is associated with higher oxidative stress and LVEDD, suggesting that altered myocardial HK activity and subcellular redistribution might be involved in the pathogenesis of postinfarct heart failure.

Effect of physical activity on the prevalence of metabolic syndrome and left ventricular hypertrophy in apparently healthy adults.

BACKGROUND/PURPOSE: Metabolic syndrome and left ventricular hypertrophy (LVH) carry high cardiovascular risks. We performed a cross-sectional study to evaluate the effect of different amounts of physical activity (PA) on the prevalence of metabolic syndrome and LVH in our study population. METHODS: This study was a cross-sectional survey of 1494 apparently healthy subjects: 776 men with a mean age of 57.6 + 12.3 years, and 718 women with a mean age of 56.4+ 11.0 years. The metabolic syndrome was defined according to modified criteria of the National Cholesterol Education Program Adult Treatment Panel III. LVH was diagnosed by electrocardiography voltage criteria. The amount of PA was determined with a questionnaire and stratified into low, moderate or high levels. RESULTS: The prevalence of metabolic syndrome and its components was as follows: metabolic syndrome, 15.5%; obesity, 29.7%; high triglyceride level, 21.7%; low high-density lipoprotein-cholesterol level, 35.9%; high blood pressure, 56.9%; and impaired fasting glucose, 13.1%. A high amount of PA (> 14 km per week walking distance) was significantly associated with lower prevalence of metabolic syndrome [odds ratio (OR) = 0.53, p = 0.001], lower prevalence of obesity (OR = 0.56, p = 0.001), triglyceridemia (OR = 0.58, p = 0.007) and LVH (OR=0.37, p = 0.006). CONCLUSION: This study suggests that high amounts of PA are inversely correlated with the prevalence of metabolic syndrome and LVH in men and women.

Transcatheter embolization of a huge renal arteriovenous fistula with Amplatzer Vascular Plug.

A large renal arteriovenous fistula (RAF) may lead to heart failure, renal insufficiency, hematuria, and progressive increase in size of renal vessels. Here we present the case of a 67-year-old man with a huge left RAF, who suffered from exertional dyspnea, nocturnal orthopnea, and impaired renal function. The left renal vein and inferior vena cava were dilated to 4 cm. An Amplatzer Vascular Plug with the largest size of 30 mm in disk diameter was deployed to block the fistula, with balloons inflated at renal artery and vein in advance, to reduce the renal flow in order to prevent plug migration. The decrease of shunt flow after embolization was suboptimal. However, dyspnea ameliorated, which was associated with decreased cardiac murmur, subsided abdominal bruit, normalization of the lowered diastolic pressure, and better renal function. In addition, more microcoils can be applied, using the lodged plug as a framework, to achieve the best clinical improvement.

Dimethylthiourea normalizes velocity-dependent, but not force-dependent, index of ventricular performance in diabetic rats: role of myosin heavy chain isozyme.

Hydroxyl radicals and hydrogen peroxide are involved in the pathogenesis of systolic dysfunction in diabetic rats, but the precise mechanisms and the effect of antioxidant therapy in diabetic subjects have not been elucidated. We aimed to evaluate the effects of dimethylthiourea (DMTU), a potent hydroxyl radical scavenger, on both force-dependent and velocity-dependent indexes of cardiac contractility in streptozotocin (STZ)-induced early and chronic diabetic rats. Seventy-two hours and 8 wk after STZ (55 mg/kg) injection, diabetic rats were randomized to either DMTU (50 mg x kg(-1) x day(-1) ip) or vehicle treatment for 6 and 12 wk, respectively. All rats were then subjected to invasive hemodynamic studies. Maximal systolic elastance (E(max)) and maximum theoretical flow (Q(max)) were assessed by curve-fitting techniques in terms of the elastance-resistance model. Both normalized E(max) (E(maxn)) and afterload-adjusted Q(max) (Q(maxad)) were depressed in diabetic rats, concomitant with altered myosin heavy chain (MHC) isoform composition and its upstream regulators, such as myocyte enhancer factor-2 (MEF-2) and heart autonomic nervous system and neural crest derivatives (HAND). In chronic diabetic rats, DMTU markedly attenuated the impairment in Q(maxad) and normalized the expression of MEF-2 and eHAND and MHC isoform composition but exerted an insignificant benefit on E(maxn). Regarding preventive treatment, DMTU significantly ameliorated both E(maxn) and Q(maxad) in early diabetic rats. In conclusion, our study shows that DMTU has disparate effects on Q(maxad) and E(maxn) in chronic diabetic rats. The advantage of DMTU in chronic diabetic rats might involve normalization of MEF-2 and eHAND, as well as reversal of MHC isoform switch.

Stent graft used to rescue coronary rupture during percutaneous coronary intervention for myocardial bridge.

Myocardial bridge (MB) is a congenital variation of the coronary arteries and the segment of the coronary artery through myocardium is compressed during systole. Although it is relatively asymptomatic, percutaneous coronary intervention (PCI) may be necessary to relieve symptoms. Perforation or frank rupture of coronary arteries occurs rarely in patients undergoing percutaneous coronary intervention. We report the coronary rupture in a case with myocardial bridge which occurred during percutaneous coronary intervention. We deployed a stent graft to successfully rescue the rupture of the distal segment of left anterior descending coronary artery (LAD-D) with myocardial bridge (MB).

Catastrophic complication of stent perforation in a uremic patient with acute myocardial infarction.

Catheter-induced coronary artery dissection is a rare but devastating complication of coronary angiography and percutaneous coronary intervention (PCI). Complications during PCI include coronary artery dissection, intramural hematoma, coronary artery perforation, and occlusion of branch vessels. Stent perforation is more unusual and potentially fatal. Here, we report a 68-year-old uremic woman who underwent primary PCI for her acute myocardial infarction. Unfortunately, dissection of the left proximal coronary artery by a guide catheter, followed by stent implantation, resulted in stent perforation through the middle left coronary artery and severe laceration of the left coronary orifice. Cardiogenic shock leading to cardiac arrest occurred. Emergency coronary artery bypass grafting and aortomy for left coronary orifice repair were conducted. The patient's postoperative course was uneventful, and she was discharged 15 days after surgery. From the successful outcome in this patient, we speculate that both better selection of patients and lesions for angioplasty and surgical standby may prove to be life-saving and effectively decrease subsequent mortality for patients experiencing devastating complications during PCI.

Human parvovirus b19 infection in patients with coronary atherosclerosis.

BACKGROUND AND AIMS: The identification of possible pathogens for an infectious etiology of atherosclerotic coronary artery disease (CAD) is an expanding field. The present study was undertaken to explore the role of parvovirus B19, a potent infectious agent. METHODS: A total of 565 patients were analyzed (90 patients with CAD, and 475 controls). Serologic analysis for human paravovirus B19 (B19) specific IgM and IgG was carried out in all patients. In addition, tissue specimens were obtained from five patients who received heart transplants. Direct in situ polymerase chain reaction (PCR) and immunocytochemistry were performed in the samples to localize B19 DNA. RESULTS: Enzyme immunoassay showed that the seropositive rate of anti-B19 IgG in patients with CAD was 1.5- to 2.7-fold more frequent than in healthy controls. Clinical characteristics did not affect the prevalence of seropositivity for B19. However, anti-B19 IgM and B19-specific DNA were not detected in healthy or individuals with CAD. Furthermore, nonradioactive in situ PCR found that the majority of B19-specific DNA was located in the endothelial cells of the thickened intima. CONCLUSIONS: Our results first demonstrate a seroepidemiological and histopathological association between chronic B19 infection and CAD, suggesting that B19 infection may have a potential role in the pathogenesis of coronary atherosclerosis.

Joint effects of N-terminal pro-B-type-natriuretic peptide and C-reactive protein vs angiographic severity in predicting major adverse cardiovascular events and clinical restenosis after coronary angioplasty in patients with stable coronary artery disease.

BACKGROUND: This study was designed to evaluate the joint effects of plasma C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) vs coronary angiographic severity on cardiovascular risk stratification. METHODS AND RESULTS: A total of 345 patients with stable coronary artery disease (CAD) were recruited after successful percutaneous coronary intervention (PCI). Endpoints were major adverse cardiovascular events (MACE) and cumulative clinical restenosis rate after 18-36-month follow-up. Plasma NT-proBNP and CRP levels were among the strongest predictors of MACE. Adjusted hazard ratios of MACE according to combined biomarkers were 2.4 (p=0.05) for elevated CRP only, 5.22 (p<0.001) for elevated NT-proBNP only, and 7.04 (p<0.001) for elevation of both. The differential capacity using both plasma CRP and NT-proBNP in a receiver-operating-characteristics curve analysis (area under curve, AUC: 0.82) was significantly higher than using either biomarker alone or conventional risk factors (AUC: 0.67). Significant predictors of clinical restenosis were plasma NT-proBNP and the Gensini score. The combination of NT-proBNP and the Gensini score was the strongest predictor (AUC: 0.77) for clinical restenosis. CONCLUSIONS: Plasma NT-proBNP, CRP, and the Gensini score are complementary in risk stratification. Combined use of these biomarkers has provided substantial extra information to conventional risk factors in stable CAD patients.

Renin-angiotensin system gene polymorphisms and atrial fibrillation: a regression approach for the detection of gene-gene interactions in a large hospitalized population.

OBJECTIVES: To test the association between renin-angiotensin system gene variants and atrial fibrillation (AF) using a regression approach. METHODS: A total of 1,236 consecutive patients (227 with AF and 1,009 with normal sinus rhythm as controls) were recruited. Angiotensin-converting enzyme (ACE) gene I/D polymorphism; T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen (AGT) gene, and A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects and to detect gene-gene interactions by incorporating interaction terms in the model. RESULTS: In single-locus analyses, no locus was associated with AF. After adjustment for AF risk factors, we found significant differences in the global AGT gene haplotype profile (the global score statistic = 30.364, p = 0.001) and individual haplotype frequencies between AF patients and controls. Furthermore, significant 2-way gene-gene interactions between ACE I/D polymorphism and AGT gene haplotypes and between AT1R A1166C polymorphism and AGT gene haplotypes, and 3-way interaction between ACE I/D, AT1R A1166C and AGT gene haplotypes were detected. CONCLUSIONS: These results are compatible with the concept of multilocus and multigene effects in determining the risk of complex diseases such as AF, which would be missed with conventional single-locus approaches.

Negative sequence voltages in spontaneous atrial fibrillation or flutter.

BACKGROUND: The patho-physiology of initiation of atrial fibrillation (af) or flutter (AF) is not known. Would it be possible that the real explanation is hidden in physics territory but not in medicine? Could it be possible that the heart behaves like a biological generator in physics? Can an abnormal inscription direction (AID) or an abnormal slow conduction (ASC) of the P loop explain the genesis of af or AF? METHODS: A total of 160 emergency Frank vectorcardiographic tracings was recorded by one physician from 55 patients with acute myocardial infarction. RESULTS: Thirty (54%) patients had abnormal inscription direction of the P loop. Seven (13%) among 55 patients developed af or AF. Six of the seven had AID of the P loop. All seven had right or left atrial enlargement. They were among 50 patients (91%) with abnormal atrium enlargement. Four among the seven had ASC of the P loop. There were 27 patients (49%) among the total 55 with ASC of the P loop. CONCLUSIONS: The heart is a biological generator, which has also inherited the same problems as generators. The types of figure-of-eight or clockwise rotation of the P loop, which are linked with the partial or complete negative sequence in physics have been documented. Based on negative sequence voltages in physics, a new theory of af, AF, or atrial premature contraction has been proposed.

Renin-angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation.

OBJECTIVES: Local atrial tissue angiotensin II (AngII) level is elevated in atrial fibrillation (AF), but the mechanism is unknown. We hypothesized that atrial myocytes express all components of the renin-angiotensin system (RAS) and investigated whether rapid depolarization alone is sufficient to increase paracrine AngII production by up-regulating RAS component expression. METHODS: In the HL-1 atrial cell line, rapid depolarization was induced by rapid field electrical stimulation (RES) at 1.0 V/cm and 600/min (10 Hz) in atrial HL-1 cells. In a pig model of AF, AF was induced by atrial pacing at 600/min in 10 adult pigs and 10 sham-operated pigs for comparison. RESULTS: In atrial myocytes, RES induced a sustained elevation of intracellular calcium, and up-regulation of angiotensin-converting enzyme (ACE), chymase and angiotensinogen, resulting in increased AngII production. RES-induced AngII production was attenuated by enalapril [ACE inhibitor (ACEI)] and chymostatin (chymase inhibitor). Conditioned medium from RES-stimulated atrial myocytes increased [3H]leucine uptake and atrial natriuretic peptide expression in atrial myocytes, and [3H]proline uptake and collagen type 1 alpha 1 expression in atrial fibroblasts. Both were attenuated by co-incubation with the AngII type 1 receptor blocker (ARB) losartan. In the porcine model, significant structural changes and a similar pattern of changes of RAS components were noted in AF pigs. CONCLUSIONS: Atrial cells expressed all components of RAS and rapid depolarization alone was sufficient to up-regulate RAS components, increase paracrine AngII production and induce atrial structural changes, which are attenuated by ACEI, ARB and chymase inhibitor.

Angiotensin II activates signal transducer and activators of transcription 3 via Rac1 in atrial myocytes and fibroblasts: implication for the therapeutic effect of statin in atrial structural remodeling.

BACKGROUND: Recently, activation of the local renin-angiotensin system and mitogen-activated protein kinase pathways in atrial myocardium has been found to play an important role in atrial structural remodeling related to atrial fibrillation. Another important mediator of the angiotensin II (Ang II) effect is the Janus kinase/signal transducers and activators of transcription (STAT) pathway, which has never been characterized in the atrium. METHODS AND RESULTS: In cultured atrial myocytes and fibroblasts, Ang II induced tyrosine phosphorylation of STAT3 through a Rac1-dependent mechanism, which was inhibited by dominant-negative Rac1, losartan, and simvastatin. In atrial myocytes, activation of STAT3 by Rac1 was mediated by direct association of Rac1 with STAT3; however, in atrial fibroblasts, it was mediated by an indirect paracrine effect. Constitutively active STAT3 increased protein synthesis, and dominant-negative STAT3 abrogated Ang II-induced protein synthesis in atrial myocytes and fibroblasts. Rats infused long term with Ang II exhibited higher levels of activated Rac1, phospho-STAT3, collagen synthesis, and atrial fibrosis in the atria, all of which were attenuated by oral losartan and simvastatin. In human atrial tissues from patients with atrial fibrillation, Ang II and phospho-STAT3 levels were also elevated. CONCLUSIONS: The Ang II/Rac1/STAT3 pathway is an important signaling pathway in the atrial myocardium to mediate atrial structural remodeling, and losartan and statin may be able to reverse Ang II-induced atrial structural remodeling in atrial fibrillation.

Vegetation on patent foramen ovale presenting as a cryptogenic brain abscess.

This paper describes a case of 51-year-old man with a vegetation on his patent foramen ovale presenting with a cryptogenic brain abscess. He received surgical evacuation and was successfully managed with septal occlusion. This is the first reported case of cryptogenic brain abscess caused by a vegetation on a patent foramen ovale directly documented with transesophageal echocardiography.

Temporal changes in cardiac force- and flow-generation capacity, loading conditions, and mechanical efficiency in streptozotocin-induced diabetic rats.

Diabetes mellitus may result in impaired cardiac contractility, but the underlying mechanisms remain unclear. We aimed to investigate the temporal alterations in cardiac force- and flow-generation capacity and loading conditions as well as mechanical efficiency in the evolution of systolic dysfunction in streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats were randomized into control and STZ-induced diabetic groups. Invasive hemodynamic studies were done at 8, 16, and 22 wk post-STZ injection. Maximal systolic elastance (E(max)) and maximum theoretical flow (Q(max)) were assessed by curve-fitting techniques, and ventriculoarterial coupling and mechanical efficiency were assessed by a single-beat estimation technique. In contrast to early occurring and persistently depressed E(max), Q(max) progressively increased with time but was decreased at 22 wk post-STZ injection, which temporally correlated with the changes in cardiac output. The favorable loading conditions enhanced stroke volume and Q(max), whereas ventriculoarterial uncoupling attenuated the cardiac mechanical efficiency in diabetic animals. The changes in E(max) and Q(max) are discordant during the progression of contractile dysfunction in the diabetic heart. In conclusion, our study showed that depressed Q(max) and cardiac mechanical efficiency, occurring preceding overt systolic heart failure, are two major determinants of deteriorating cardiac performance in diabetic rats.

Human C-reactive protein (CRP) gene 1059G>C polymorphism is associated with plasma CRP concentration in patients receiving coronary angiography.

BACKGROUND/PURPOSE: Elevation of C-reactive protein (CRP) level is associated with increased risk of cardiovascular events. The 1059 G>C polymorphism in exon 2 of the CRP gene has been shown to affect plasma concentration of CRP. We want to elucidate the effect of this polymorphism on the development of coronary artery disease (CAD) among the Chinese population in Taiwan. METHODS: We scrutinized 536 patients undergoing coronary angiography (365 patients with CAD and 171 controls with patent coronaries) and evaluated the association of CRP gene 1059 G>C polymorphism with CAD. Genotyping of the polymorphism was performed by polymerase chain reaction and MaeIII restriction enzyme digestion. RESULTS: The CC genotype was associated with lower plasma CRP concentration (GG, 6.5+/-5.8; GC, 3.3+/-4.4; CC, 2.3+/-3.1 mg/L; p=0.02). Subjects with CAD or myocardial infarction (MI) had significantly higher plasma CRP concentration than that in controls (CAD vs. controls, 8.9+/-18.9 vs. 3.3+/-7.2 mg/L; p<0.001), while patients with MI showed higher CRP when compared to those with chronic stable angina (13.5+/-22.9 vs. 5.2+/-14.1 mg/L; p<0.001). However, this polymorphism was not associated with CAD in our population. CONCLUSION: Our data suggest that human CRP gene 1059 G>C polymorphism is associated with plasma CRP concentration among Chinese in Taiwan receiving coronary angiography.