Right ventricular abnormalities assessed by myocardial single-photon emission computed tomography using technetium-99m sestamibi/tetrofosmin in right ventricle-originated ventricular tachyarrhythmias

AbstractOBJECTIVESWe sought to determine whether right ventricular (RV) perfusion imaging with technetium-99m (Tc-99m) sestamibi or tetrofosmin single-photon emission computed tomography has diagnostic benefit for RV-originated ventricular tachyarrhythmias (RVT).BACKGROUNDIdentification of RV abnormalities is clinically important to establish RVT etiology.METHODSForty-seven patients with RVT (23 with idiopathic and 24 with organic RVT due to arrhythmogenic RV or dilated cardiomyopathy, cardiac sarcoidosis or myocarditis) were compared to 25 control subjects. Right ventricular uptake score, as assessed by modified tomographic imaging, and regional RV count relative to peak left ventricular (LV) count (RV/LV count ratio) were compared with RV regional and global function.RESULTSRegional RV uptake score correlated well with the RV/LV count ratio, and segmental abnormality was more frequently (p = 0.001) detected in the organic RVT group (22 [92%] of 24 patients) than in the idiopathic RVT group (4 [17%] of 23 patients) or the control group (8 [32%] of 25 patients). The total RV score (8.4 ± 3.8) in the organic RVT group was significantly lower than that in the idiopathic RVT group (15.6 ± 1.6) or the control group (15.1 ± 1.8). The total RV score correlated with RV EF (r = 0.702, p < 0.001). A total RV score <12 differentiated the organic RVT group from the other two groups, with a sensitivity of 79% and a specificity of 100%. The asynergic RV regions had a significantly lower RV/LV count ratio and RV score as compared with the nonasynergic regions and were identified by RV assessment, with a sensitivity of 76.1% and a specificity of 76.6%.CONCLUSIONSRight ventricular perfusion tomography using a Tc-99m–labeled tracer is clinically useful for the noninvasive detection of RV myocardial damage in patients with RVT and for differentiating organic from idiopathic RVT

Inhibition of Plasma Kallikrein with Aprotinin in porcine endotoxin Shock

Activation of the contact phase of coagulation has been implicated in the pathogenesis of septic shock. We wanted to determine if inhibition of plasma kallikrein can prevent arterial hypotension and liberation of kinins from kininogen, induced by an infusion of bacterial lipopolysaccharide (LPS) in anesthetized, ventilated 20-kg pigs. The LPS was given IV in a dose of 5 [mu]g/kg/h for 8 hours. The plasma kallikrein inhibitor aprotinin, 537 [mu]mol, was given IV during 8 hours, resulting in plasma levels above 10 [mu]mol/L. Ten animals (SA) received LPS and aprotinin and ten randomized controls (SC) received LPS and saline. Kinin-containing kininogen was determined on the basis of the amount of kinin releasable in plasma samples by incubation with trypsin. Kininogen decreased to 58% +/- 4% of the baseline value without any difference between groups. This may indicate participation of other processes than degradation by plasma kallikrein in the decrease of kininogen. Arterial blood pressure was higher at 7 hours in the SA animals than in the SC group (101% +/- 11% vs. 68% +/- 8%; mean +/- SEM; p = 0.026). Fibrin monomer and C3adesArg plasma levels were attenuated by aprotinin treatment. These findings underscore the important role of the contact system in LPS shock

Mitochondrial ATP-sensitive K+channels play a role in cardioprotection by Na+-H+exchange inhibition against ischemia/reperfusion injury

AbstractOBJECTIVESThe possible role of the ATP-sensitive potassium (KATP) channel in cardioprotection by Na+-H+exchange (NHE) inhibition was examined.BACKGROUNDThe KATPchannel is suggested to be involved not only in ischemic preconditioning but also in some pharmacological cardioprotection.METHODSInfarction was induced by 30-min coronary occlusion in rabbit hearts in situ or by 30-min global ischemia in isolated hearts. Myocardial stunning was induced by five episodes of 5-min ischemia/5-min reperfusion in situ. In these models, the effects of NHE inhibitors (cariporide and ethylisopropyl-amiloride [EIPA]) and the changes caused by KATPchannel blockers were assessed. In another series of experiments, the effects of EIPA on mitochondrial KATP(mito-KATP) and sarcolemmal KATP(sarc-KATP) channels were examined in isolated cardiomyocytes.RESULTSCariporide (0.6 mg/kg) reduced infarct size in situ by 40%, and this effect was abolished by glibenclamide (0.3 mg/kg), a nonselective KATPchannel blocker. In vitro, 1 μM cariporide limited infarct size by 90%, and this effect was blocked by 5-hydroxydecanoate (5-HD), a mito-KATPchannel blocker but not by HMR1098, a sarc-KATPchannel blocker. Infarct size limitation by 1 μM EIPA was also prevented by 5-HD. Cariporide attenuated regional contractile dysfunction by stunning, and this protection was abolished by glibenclamide and 5-HD. Ethylisopropyl amiloride neither activated the mito-KATPchannel nor enhanced activation of this channel by diazoxide, a KATPchannel opener.CONCLUSIONSOpening of the mito-KATPchannel contributes to cardioprotection by NHE inhibition, though the interaction between NHE and this KATPchannel remains unclear

Protease inhibitors extracted from caesalpinia echinata lam. Affect kinin release during lung inflammation

Inflammation is an essential process in many pulmonary diseases in which kinins are generated by protease action on kininogen, a phenomenon that is blocked by protease inhibitors. We evaluated kinin release in an in vivo lung inflammation model in rats, in the presence or absence of CeKI (C. echinata kallikrein inhibitor), a plasma kallikrein, cathepsin G, and proteinase-3 inhibitor, and rCeEI (recombinant C. echinata elastase inhibitor), which inhibits these proteases and also neutrophil elastase. Wistar rats were intravenously treated with buffer (negative control) or inhibitors and, subsequently, lipopolysaccharide was injected into their lungs. Blood, bronchoalveolar lavage fluid (BALF), and lung tissue were collected. In plasma, kinin release was higher in the LPS-treated animals in comparison to CeKI or rCeEI groups. rCeEI-treated animals presented less kinin than CeKI-treated group. Our data suggest that kinins play a pivotal role in lung inflammation and may be generated by different enzymeshowever, neutrophil elastase seems to be the most important in the lung tissue context. These results open perspectives for a better understanding of biological process where neutrophil enzymes participate and indicate these plant inhibitors and their recombinant correlates for therapeutic trials involving pulmonary diseases.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [04/11015-0, 07/55496-0, 01/02457-0]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [304923/2006-0, 304719/2009-9]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/Ministerio da Educacao Superior de Cuba (CAPES/MES), Brazil [011/06, 077/09]Department of Biochemistry, Universidade Federal de S˜ao Paulo, Rua Trˆes de Maio, No. 100, 04044-020 S˜ao Paulo, SP, BrazilSchool of Arts, Sciences and Humanities, Universidade de São Paulo, Avenida Arlindo Bettio, No. 1000, 03828-000 São Paulo, SP, BrazilDepartment of Marine Sciences, Universidade Federal de São Paulo, Rua Doutor Carvalho de Mendonça, No. 144, 11070-100 Santos, SP, BrazilJapan Health Care College, Sinei 434-1, Kiyota-ku, Sapporo, JapanDepartment of Marine Sciences, Universidade Federal de São Paulo, Rua Doutor Carvalho de Mendonça, No. 144, 11070-100 Santos, SP, BrazilFAPESP: 04/11015-0FAPESP: 07/55496-0FAPESP: 01/02457-0CNPq: 304923/2006-0CNPq: 304719/2009-9CAPES/MES: 011/06 and 077/09Web of Scienc

Serum Fatty Acid-Binding Protein 4 Is a Predictor of Cardiovascular Events in End-Stage Renal Disease

BACKGROUND: Fatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown that FABP4 is secreted from adipocytes and that FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the impact of FABP4 concentrations on prognosis. We tested the hypothesis that FABP4 level predicts prognosis of patients with end-stage renal disease (ESRD), a group at high risk for atherosclerosis-associated morbidity and mortality. METHODS AND RESULTS: Biochemical markers including FABP4 were determined in 61 ESRD patients on chronic hemodialysis (HD). Serum FABP4 level in females (404.2±30.5 ng/ml) was significantly higher than that in males (315.8±30.0 ng/ml), and the levels in ESRD patients were about 20-times higher than those in age-, gender- and body mass index (BMI)-matched control subjects with normal renal function. FABP4 level was decreased by 57.2% after HD and was positively correlated with blood pressure, BMI, and levels of lipids and insulin. Multiple regression analysis indicated that HD duration, BMI, and triglycerides level were independent determinants for FABP4 level. ESRD patients with high FABP4 levels had higher cardiovascular mortality during the 7-year follow-up period. Cox proportional hazard regression analysis showed that logarithmically transformed FABP4 level was an independent predictor of cardiovascular death adjusted for age, gender, HD duration, BMI, and triglycerides level (hazard ratio, 7.75; 95% CI, 1.05-25.31). CONCLUSION: These findings suggest that FABP4 level, being related to adiposity and metabolic disorders, is a novel predictor of cardiovascular mortality in ESRD

Cardiovascular events in Japanese asymptomatic patients with type 2 diabetes: a 1-year interim report of a J-ACCESS 2 investigation using myocardial perfusion imaging

金沢大学医薬保健研究域医学系Purpose Diabetic patients have a high risk for cardiovascular events. The role of myocardial perfusion imaging was investigated in asymptomatic diabetic patients to evaluate short-term prognosis in a Japanese population. Methods A total of 506 asymptomatic patients ≥50 years of age who had carotid artery maximum intima-media thickness ≥1.1 mm, urinary albumin excretion of ≥30 mg/g creatinine, with additional criteria of abdominal obesity, low HDL cholesterol, high triglyceride level, and hypertension were enrolled and followed up over a 3-year period. Gated SPECT with stress-rest protocol was performed and analyzed by summed defect scores and QGS software. One-year cardiovascular events were analyzed. Results Myocardial ischemia was observed in 17% of patients, and abnormal perfusion findings of ischemia and/or scar were observed in 32% of patients. By the end of the 1-year follow-up, 33 (6.5%) cardiovascular events occurred including 6 all-cause deaths. Patients with summed stress score (SSS) >8 had a higher incidence of either death or cardiovascular events. Event-free survival rates for SSS 0–3, 4–8, 9–13, and ≥14 were 0.96, 0.95, 0.82, and 0.76, respectively. Multivariate Cox regression analysis showed that significant variables were SSS, history of cerebrovascular accident, and electrocardiographic abnormality at rest. Conclusion The 1-year interim summary showed that cardiovascular events were significantly higher in patients with SPECT abnormality, although hard cardiac event rate was relatively low. Targeted treatment strategy is required for asymptomatic but potentially high-risk diabetic patients

Large-scale cohort study on the relationship between serum lipid concentrations and risk of cerebrovascular disease under low-dose simvastatin in Japanese patients with hypercholesterolemia: Sub-analysis of the Japan Lipid Intervention Trial (J-LIT)

金沢大学大学院医学系研究科　Background: The Japan Lipid Intervention Trial was a nationwide cohort study of 52,421 hypercholesterolemic patients treated with open-labeled simvastatin for 6 years under standard clinical practices. Cerebrovascular disease (CVD) is one of the leading causes of death in Japan, but the effect of hypercholesterolemia on CVD has not been well established in Japanese patients. This study aimed to determine the relationship between the risk of CVD and serum lipid concentrations during treatment in Japan. Methods and Results: Patients were treated with 5-10 mg/day of simvastatin and all, including those who discontinued simvastatin for any reason, had their lipid concentrations and incidence of CVD monitored for 6 years. Data of 41,088 patients were analyzed in this study, excluding those who had a history of coronary heart disease or CVD. The risk of cerebral infarction was higher in patients whose mean total cholesterol concentrations during treatment were ≥240 mg/dl, low-density lipoprotein cholesterol concentrations ≥160 mg/dl, triglycerides ≥150 mg/dl and high-density lipoprotein cholesterol concentrations <40 mg/dl. There was no obvious correlation between cerebral hemorrhage and serum lipid concentrations. Conclusion: Improvement of serum lipid concentrations is important for reducing the incidence of cerebral infarction