Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032887.55215.5C
T. Nomoto, T. Nishina, S. Miwa, H. Tsuneyoshi, I. Maruyama, K. Nishimura, M. Komeda
BackgroundWe reported in a previous study that the initial effects of left ventricular (LV) repair (LVR) for LV aneurysm were not long lasting. Angiotensin-converting enzyme inhibitor (ACE-I) is known to attenuate remodeling after myocardial infarction, and could be effective after LVR. Methods and ResultsLeft ventricular aneurysms were developed in rats after left anterior descending artery ligation. Rats were divided into 3 groups: sham operation with ACE-I (lisinopril 10 mg/kg/d) (n=10; group A), LVR (by plicating the LV aneurysm) with placebo (n=8; group R), and LVR with ACE-I (n=10; group RA). LV function was evaluated by echocardiography and catheterization. Oxidative stress in the myocardium was estimated by immunohistochemistry for 8-hydroxy-2′-deoxyguanosine. One week after LVR, LV end-diastolic area was smaller and fractional area change was better in the 2 LVR groups. Four weeks after LVR, LV end-diastolic area, and fractional area change deteriorated in group R but not so much in group RA; E-max was higher in group RA (0.79±0.20 mm Hg/mL) than in groups A (0.25±0.03 mm Hg/mL;P <0.01) and group R (0.27±0.03 mm Hg/mL;P <0.01). Oxidative stress was much lower in the 2 ACE-I groups. ConclusionsLVR improved LV size and systolic function only in the early phase. Adjuvant use of ACE-I was useful for preventing redilation and maintaining LV systolic function, was associated with suppressed oxidative stress, and may make LVR a more effective surgical procedure for LV aneurysm.
我们在之前的一项研究中报道，左室(LV)修复(LVR)治疗左室动脉瘤的初始效果并不持久。已知血管紧张素转换酶抑制剂(ACE-I)可以减轻心肌梗死后的重构，并且可能在LVR后有效。方法与结果大鼠左前降支结扎术后发生左心室动脉瘤。大鼠分为3组:假手术给药ACE-I(赖诺普利10 mg/kg/d) (n=10;A组)，LVR(通过复制左室动脉瘤)与安慰剂(n=8;R组)，LVR组与ACE-I组(n=10;RA)。通过超声心动图和导管检查评估左室功能。8-羟基-2′-脱氧鸟苷免疫组化法测定心肌氧化应激。LVR术后1周，2个LVR组左室舒张末期面积较小，分数面积变化较好。LVR术后4周，R组左室舒张末期面积、分数区面积变化变差，RA组无明显变化;RA组E-max(0.79±0.20 mm Hg/mL)高于A组(0.25±0.03 mm Hg/mL, P <0.01)和R组(0.27±0.03 mm Hg/mL, P <0.01)。2个ACE-I组的氧化应激明显降低。结论slvr仅在早期改善左室大小和收缩功能。辅助使用ACE-I有助于预防再松弛和维持左室收缩功能，与抑制氧化应激有关，并可能使LVR成为左室动脉瘤更有效的手术方法。
{"title":"Angiotensin-Converting Enzyme Inhibitor Helps Prevent Late Remodeling After Left Ventricular Aneurysm Repair in Rats","authors":"T. Nomoto, T. Nishina, S. Miwa, H. Tsuneyoshi, I. Maruyama, K. Nishimura, M. Komeda","doi":"10.1161/01.CIR.0000032887.55215.5C","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032887.55215.5C","url":null,"abstract":"BackgroundWe reported in a previous study that the initial effects of left ventricular (LV) repair (LVR) for LV aneurysm were not long lasting. Angiotensin-converting enzyme inhibitor (ACE-I) is known to attenuate remodeling after myocardial infarction, and could be effective after LVR. Methods and ResultsLeft ventricular aneurysms were developed in rats after left anterior descending artery ligation. Rats were divided into 3 groups: sham operation with ACE-I (lisinopril 10 mg/kg/d) (n=10; group A), LVR (by plicating the LV aneurysm) with placebo (n=8; group R), and LVR with ACE-I (n=10; group RA). LV function was evaluated by echocardiography and catheterization. Oxidative stress in the myocardium was estimated by immunohistochemistry for 8-hydroxy-2′-deoxyguanosine. One week after LVR, LV end-diastolic area was smaller and fractional area change was better in the 2 LVR groups. Four weeks after LVR, LV end-diastolic area, and fractional area change deteriorated in group R but not so much in group RA; E-max was higher in group RA (0.79±0.20 mm Hg/mL) than in groups A (0.25±0.03 mm Hg/mL;P <0.01) and group R (0.27±0.03 mm Hg/mL;P <0.01). Oxidative stress was much lower in the 2 ACE-I groups. ConclusionsLVR improved LV size and systolic function only in the early phase. Adjuvant use of ACE-I was useful for preventing redilation and maintaining LV systolic function, was associated with suppressed oxidative stress, and may make LVR a more effective surgical procedure for LV aneurysm.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"240 1","pages":"I-115-I-119"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90503686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032908.33237.B1
W. Mahle, F. Tavani, R. Zimmerman, S. Nicolson, Kristin K. Galli, J. Gaynor, R. Clancy, L. Montenegro, T. Spray, R. Chiavacci, G. Wernovsky, C. Kurth
BackgroundNeuorological deficits are observed in patients with congenital heart disease (CHD) before and after neonatal surgery, the etiology being multifactorial. To understand the impact of preoperative events and to characterize the evaluation of neurological injury, we performed serial magnetic resonance imaging (MRI) studies of the brain in a cohort of neonates undergoing open-heart surgery. Methods and ResultsTwenty-four term neonates with CHD were studied prospectively with brain MRI: before surgery, within 2 weeks of surgery, and several months after surgery. Preoperative MRI examinations showed periventricular leukomalacia (PVL) in 4 patients (16%) and infarct in 2 subjects (8%). MR spectroscopy was performed in 19 subjects preoperatively and revealed elevated brain lactate in 53%. An early postoperative MRI (n=21) identified new PVL in 48%, new infarct in 19%, and new parenchymal hemorrhage in 33%. New lesions or worsening of preoperative lesions occurred in 67% of subjects. No patient- or procedure-related factors for the development of early postoperative lesions were identified. A late postoperative MRI (n=17) demonstrated resolution of early lesions in 8 and mild cerebral atrophy in 2. ConclusionsMild ischemic lesions, primarily in the form of PVL, occur in a number of neonates with CHD before surgery and >50% of patients postoperatively. Resolution of these lesions is common 4 to 6 months after surgery. Longer-term follow-up is needed to determine the significance of perioperative ischemic lesions on functional outcome.
{"title":"An MRI Study of Neurological Injury Before and After Congenital Heart Surgery","authors":"W. Mahle, F. Tavani, R. Zimmerman, S. Nicolson, Kristin K. Galli, J. Gaynor, R. Clancy, L. Montenegro, T. Spray, R. Chiavacci, G. Wernovsky, C. Kurth","doi":"10.1161/01.CIR.0000032908.33237.B1","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032908.33237.B1","url":null,"abstract":"BackgroundNeuorological deficits are observed in patients with congenital heart disease (CHD) before and after neonatal surgery, the etiology being multifactorial. To understand the impact of preoperative events and to characterize the evaluation of neurological injury, we performed serial magnetic resonance imaging (MRI) studies of the brain in a cohort of neonates undergoing open-heart surgery. Methods and ResultsTwenty-four term neonates with CHD were studied prospectively with brain MRI: before surgery, within 2 weeks of surgery, and several months after surgery. Preoperative MRI examinations showed periventricular leukomalacia (PVL) in 4 patients (16%) and infarct in 2 subjects (8%). MR spectroscopy was performed in 19 subjects preoperatively and revealed elevated brain lactate in 53%. An early postoperative MRI (n=21) identified new PVL in 48%, new infarct in 19%, and new parenchymal hemorrhage in 33%. New lesions or worsening of preoperative lesions occurred in 67% of subjects. No patient- or procedure-related factors for the development of early postoperative lesions were identified. A late postoperative MRI (n=17) demonstrated resolution of early lesions in 8 and mild cerebral atrophy in 2. ConclusionsMild ischemic lesions, primarily in the form of PVL, occur in a number of neonates with CHD before surgery and >50% of patients postoperatively. Resolution of these lesions is common 4 to 6 months after surgery. Longer-term follow-up is needed to determine the significance of perioperative ischemic lesions on functional outcome.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"28 1","pages":"I-109-I-114"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86462307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-24DOI: 10.1161/01.CIR.0000032907.33237.55
S. Chatterjee, A. S. Stewart, L. Bish, V. Jayasankar, Elizabeth M. Kim, T. Pirolli, J. Burdick, Y. Woo, T. Gardner, H. Sweeney
BackgroundApoptosis secondary to acute ischemia and chronic remodeling is implicated as a mediator of heart failure. This study was designed to assess the effect of in vivo viral gene transfer of the anti-apoptotic factor Bcl-2 to block apoptosis and preserve ventricular geometry and function. Methods and ResultsIn a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adeno-Bcl-2 was compared with a control group receiving empty vector adeno-null. Function was assessed by echocardiography, and sonomicrometry of the border zone was compared with the normal left ventricle (LV). Animals were killed at 6 weeks, and an additional group was killed after 3 days to see whether virus administration conferred an immediate effect. Animals that were administered Bcl-2 maintained higher ejection fractions at 2, 4, and 6 weeks compared with controls. Sonomicrocrystals demonstrated greater protection of border zone fractional shortening at 6 weeks. The Bcl-2 group had superior preservation of LV geometry with less ventricular dilatation and wall thinning. There was also reduced apoptosis compared with the controls. Finally, in the animals killed at 3 days, no functional difference was observed between the Bcl-2 and control groups. ConclusionsGene transfer of Bcl-2 preserves LV function after ischemia despite the absence of an observed acute protective effect. The benefit at 6 weeks is postulated to result from a Bcl-2–mediated reduction in apoptosis and ventricular remodeling. Adeno–Bcl-2 administration offers a potential strategy to protect the heart from late postischemic heart failure.
{"title":"Viral Gene Transfer of the Antiapoptotic Factor Bcl-2 Protects Against Chronic Postischemic Heart Failure","authors":"S. Chatterjee, A. S. Stewart, L. Bish, V. Jayasankar, Elizabeth M. Kim, T. Pirolli, J. Burdick, Y. Woo, T. Gardner, H. Sweeney","doi":"10.1161/01.CIR.0000032907.33237.55","DOIUrl":"https://doi.org/10.1161/01.CIR.0000032907.33237.55","url":null,"abstract":"BackgroundApoptosis secondary to acute ischemia and chronic remodeling is implicated as a mediator of heart failure. This study was designed to assess the effect of in vivo viral gene transfer of the anti-apoptotic factor Bcl-2 to block apoptosis and preserve ventricular geometry and function. Methods and ResultsIn a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adeno-Bcl-2 was compared with a control group receiving empty vector adeno-null. Function was assessed by echocardiography, and sonomicrometry of the border zone was compared with the normal left ventricle (LV). Animals were killed at 6 weeks, and an additional group was killed after 3 days to see whether virus administration conferred an immediate effect. Animals that were administered Bcl-2 maintained higher ejection fractions at 2, 4, and 6 weeks compared with controls. Sonomicrocrystals demonstrated greater protection of border zone fractional shortening at 6 weeks. The Bcl-2 group had superior preservation of LV geometry with less ventricular dilatation and wall thinning. There was also reduced apoptosis compared with the controls. Finally, in the animals killed at 3 days, no functional difference was observed between the Bcl-2 and control groups. ConclusionsGene transfer of Bcl-2 preserves LV function after ischemia despite the absence of an observed acute protective effect. The benefit at 6 weeks is postulated to result from a Bcl-2–mediated reduction in apoptosis and ventricular remodeling. Adeno–Bcl-2 administration offers a potential strategy to protect the heart from late postischemic heart failure.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"2 1","pages":"I-212-I-217"},"PeriodicalIF":0.0,"publicationDate":"2002-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86620485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-03DOI: 10.1161/01.CIR.0000027820.66786.CF
Adam F.M. Stone, Michael A. Mendall, J. Kaski, Tracey M. Edger, P. Risley, J. Poloniecki, A. Camm, T. Northfield
Background—Infection with Helicobacter pylori and Chlamydia pneumoniae is associated with coronary heart disease. We conducted an intervention study using antibiotics against these bacteria in patients with acute coronary syndromes to determine whether antibiotics reduce inflammatory markers and adverse cardiac events. Methods and Results—Patients (n=325) admitted with acute myocardial infarction or unstable angina (acute coronary syndromes) were randomized to receive a 1-week course of 1 of 3 treatment regimens: (1) placebo; (2) amoxicillin (500 mg twice daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily); or (3) azithromycin (500 mg once daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily). Serum fibrinogen, white cell count, and high-sensitivity C-reactive protein were measured at study entry and at 1, 3, and 12 months during follow-up. Cardiac death and readmission with acute coronary syndrome were considered clinical end points. Patients were followed for 1 year. C-reactive protein levels were reduced (P =0.03) in unstable angina patients receiving amoxicillin, and fibrinogen was reduced in both patient groups receiving antibiotics (P =0.06). There were 17 cardiac deaths and 71 readmissions with acute coronary syndrome. No difference in frequency or timing of end points was observed between the 2 antibiotic groups. At 12 weeks, there was a 36% reduction in all end points in patients receiving antibiotics compared with placebo (P =0.02). This reduction persisted during the 1-year follow-up. Neither C pneumoniae nor H pylori antibody status was significantly related to response to treatment. Conclusions—Antibiotic treatment significantly reduced adverse cardiac events in patients with acute coronary syndromes, but the effect was independent of H pylori or C pneumoniae seropositivity.
{"title":"Effect of Treatment for Chlamydia pneumoniae and Helicobacter pylori on Markers of Inflammation and Cardiac Events in Patients With Acute Coronary Syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA)","authors":"Adam F.M. Stone, Michael A. Mendall, J. Kaski, Tracey M. Edger, P. Risley, J. Poloniecki, A. Camm, T. Northfield","doi":"10.1161/01.CIR.0000027820.66786.CF","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027820.66786.CF","url":null,"abstract":"Background—Infection with Helicobacter pylori and Chlamydia pneumoniae is associated with coronary heart disease. We conducted an intervention study using antibiotics against these bacteria in patients with acute coronary syndromes to determine whether antibiotics reduce inflammatory markers and adverse cardiac events. Methods and Results—Patients (n=325) admitted with acute myocardial infarction or unstable angina (acute coronary syndromes) were randomized to receive a 1-week course of 1 of 3 treatment regimens: (1) placebo; (2) amoxicillin (500 mg twice daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily); or (3) azithromycin (500 mg once daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily). Serum fibrinogen, white cell count, and high-sensitivity C-reactive protein were measured at study entry and at 1, 3, and 12 months during follow-up. Cardiac death and readmission with acute coronary syndrome were considered clinical end points. Patients were followed for 1 year. C-reactive protein levels were reduced (P =0.03) in unstable angina patients receiving amoxicillin, and fibrinogen was reduced in both patient groups receiving antibiotics (P =0.06). There were 17 cardiac deaths and 71 readmissions with acute coronary syndrome. No difference in frequency or timing of end points was observed between the 2 antibiotic groups. At 12 weeks, there was a 36% reduction in all end points in patients receiving antibiotics compared with placebo (P =0.02). This reduction persisted during the 1-year follow-up. Neither C pneumoniae nor H pylori antibody status was significantly related to response to treatment. Conclusions—Antibiotic treatment significantly reduced adverse cardiac events in patients with acute coronary syndromes, but the effect was independent of H pylori or C pneumoniae seropositivity.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"8 1","pages":"1219-1223"},"PeriodicalIF":0.0,"publicationDate":"2002-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78750186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-03DOI: 10.1161/01.CIR.0000027569.76671.A8
A. Ceriello, C. Taboga, L. Tonutti, L. Quagliaro, L. Piconi, B. Bais, R. da Ros, E. Motz
Background—Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction through oxidative stress; however, the distinct role of these two factors is a matter of debate. Methods and Results—Thirty type 2 diabetic patients and 20 normal subjects ate 3 different meals: a high-fat meal; 75 g glucose alone; and high-fat meal plus glucose. Glycemia, triglyceridemia, nitrotyrosine, and endothelial function were assayed during the tests. Subsequently, diabetics took 40 mg/d simvastatin or placebo for 12 weeks. The 3 tests were performed again at baseline, between 3 to 6 days after the start, and at the end of each study. High-fat load and glucose alone produced a decrease of endothelial function and an increase of nitrotyrosine in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters but reduced the effect on endothelial function and nitrotyrosine observed during each different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations of endothelial function and nitrotyrosine during the tests. Conclusions—This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function, suggesting oxidative stress as common mediator of such effect. Simvastatin shows a beneficial effect on oxidative stress and endothelial dysfunction, which may be ascribed to a direct effect as well as the lipid-lowering action of the drug.
{"title":"Evidence for an Independent and Cumulative Effect of Postprandial Hypertriglyceridemia and Hyperglycemia on Endothelial Dysfunction and Oxidative Stress Generation: Effects of Short- and Long-Term Simvastatin Treatment","authors":"A. Ceriello, C. Taboga, L. Tonutti, L. Quagliaro, L. Piconi, B. Bais, R. da Ros, E. Motz","doi":"10.1161/01.CIR.0000027569.76671.A8","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027569.76671.A8","url":null,"abstract":"Background—Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction through oxidative stress; however, the distinct role of these two factors is a matter of debate. Methods and Results—Thirty type 2 diabetic patients and 20 normal subjects ate 3 different meals: a high-fat meal; 75 g glucose alone; and high-fat meal plus glucose. Glycemia, triglyceridemia, nitrotyrosine, and endothelial function were assayed during the tests. Subsequently, diabetics took 40 mg/d simvastatin or placebo for 12 weeks. The 3 tests were performed again at baseline, between 3 to 6 days after the start, and at the end of each study. High-fat load and glucose alone produced a decrease of endothelial function and an increase of nitrotyrosine in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters but reduced the effect on endothelial function and nitrotyrosine observed during each different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations of endothelial function and nitrotyrosine during the tests. Conclusions—This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function, suggesting oxidative stress as common mediator of such effect. Simvastatin shows a beneficial effect on oxidative stress and endothelial dysfunction, which may be ascribed to a direct effect as well as the lipid-lowering action of the drug.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"39 1","pages":"1211-1218"},"PeriodicalIF":0.0,"publicationDate":"2002-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74081103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-03DOI: 10.1161/01.CIR.0000027139.42087.B6
N. Makita, M. Horie, Takeshi Nakamura, Tomohiko Ai, K. Sasaki, Hisataka Yokoi, M. Sakurai, I. Sakuma, H. Otani, H. Sawa, A. Kitabatake
Background—Subclinical mutations in genes associated with the congenital long-QT syndromes (LQTS) have been suggested as a risk factor for drug-induced LQTS and accompanying life-threatening arrhythmias. Recent studies have identified genetic variants of the cardiac K+ channel genes predisposing affected individuals to acquired LQTS. We have identified a novel Na+ channel mutation in an individual who exhibited drug-induced LQTS. Methods and Results—An elderly Japanese woman with documented QT prolongation and torsade de pointes during treatment with the prokinetic drug cisapride underwent mutational analysis of LQTS-related genes. A novel missense mutation (L1825P) was identified within the C-terminus region of the cardiac Na+ channel (SCN5A). The L1825P channel heterologously expressed in tsA-201 cells showed Na+ current with slow decay and a prominent tetrodotoxin-sensitive noninactivating component, similar to the gain-of-function phenotype most commonly observed for SCN5A-associated congenital LQTS (LQT3). In addition, L1825P exhibited loss of function Na+ channel features characteristic of Brugada syndrome. Peak Na+ current density observed in cells expressing L1825P was significantly diminished, and the voltage dependence of activation and inactivation was shifted toward more positive and negative potentials, respectively. Conclusions—This study demonstrates that subclinical mutations in the LQTS-related gene SCN5A may predispose certain individuals to drug-induced cardiac arrhythmias.
{"title":"Drug-Induced Long-QT Syndrome Associated With a Subclinical SCN5A Mutation","authors":"N. Makita, M. Horie, Takeshi Nakamura, Tomohiko Ai, K. Sasaki, Hisataka Yokoi, M. Sakurai, I. Sakuma, H. Otani, H. Sawa, A. Kitabatake","doi":"10.1161/01.CIR.0000027139.42087.B6","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027139.42087.B6","url":null,"abstract":"Background—Subclinical mutations in genes associated with the congenital long-QT syndromes (LQTS) have been suggested as a risk factor for drug-induced LQTS and accompanying life-threatening arrhythmias. Recent studies have identified genetic variants of the cardiac K+ channel genes predisposing affected individuals to acquired LQTS. We have identified a novel Na+ channel mutation in an individual who exhibited drug-induced LQTS. Methods and Results—An elderly Japanese woman with documented QT prolongation and torsade de pointes during treatment with the prokinetic drug cisapride underwent mutational analysis of LQTS-related genes. A novel missense mutation (L1825P) was identified within the C-terminus region of the cardiac Na+ channel (SCN5A). The L1825P channel heterologously expressed in tsA-201 cells showed Na+ current with slow decay and a prominent tetrodotoxin-sensitive noninactivating component, similar to the gain-of-function phenotype most commonly observed for SCN5A-associated congenital LQTS (LQT3). In addition, L1825P exhibited loss of function Na+ channel features characteristic of Brugada syndrome. Peak Na+ current density observed in cells expressing L1825P was significantly diminished, and the voltage dependence of activation and inactivation was shifted toward more positive and negative potentials, respectively. Conclusions—This study demonstrates that subclinical mutations in the LQTS-related gene SCN5A may predispose certain individuals to drug-induced cardiac arrhythmias.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"50 1","pages":"1269-1274"},"PeriodicalIF":0.0,"publicationDate":"2002-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78845630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-03DOI: 10.1161/01.CIR.0000028336.95629.B0
A. Michaels, M. Accad, T. Ports, W. Grossman
Background—Enhanced external counterpulsation (EECP) is a noninvasive, pneumatic technique that provides beneficial effects for patients with chronic, symptomatic angina pectoris. However, the physiological effects of EECP have not been studied directly. We examined intracoronary and left ventricular hemodynamics in the cardiac catheterization laboratory during EECP. Methods and Results—Ten patients referred for diagnostic evaluation underwent left heart catheterization and coronary angiography from the radial artery. At baseline and then during EECP, central aortic pressure, intracoronary pressure, and intracoronary Doppler flow velocity were measured using a coronary catheter, a sensor-tipped high-fidelity pressure guidewire, and a Doppler flow guidewire, respectively. Similar to changes in aortic pressure, EECP resulted in a dramatic increase in diastolic (71±10 mm Hg at baseline to 137±21 mm Hg during EECP; +93%;P <0.0001) and mean intracoronary pressures (88±9 to 102±16 mm Hg; +16%;P =0.006) with a decrease in systolic pressure (116±20 to 99±26 mm Hg; −15%;P =0.002). The intracoronary Doppler measure of average peak velocity increased from 11±5 cm/s at baseline to 23±5 cm/s during EECP (+109%;P =0.001). The TIMI frame count, a quantitative angiographic measure of coronary flow, showed a 28% increase in coronary flow during EECP compared with baseline (P =0.001). Conclusions—EECP unequivocally and significantly increases diastolic and mean pressures and reduces systolic pressure in the central aorta and the coronary artery. Coronary artery flow, determined by both Doppler and angiographic techniques, is increased during EECP. The combined effects of systolic unloading and increased coronary perfusion pressure provide evidence that EECP may serve as a potential mechanical assist device.
背景:增强体外反搏(EECP)是一种无创的气动技术，可为慢性症状性心绞痛患者提供有益的效果。然而，EECP的生理作用尚未得到直接研究。在EECP期间，我们在心导管实验室检查冠状动脉内和左心室血流动力学。方法与结果:10例确诊患者均行左心导管穿刺及桡动脉冠状动脉造影。在基线和EECP期间，分别使用冠状动脉导管、传感器尖端的高保真压力导丝和多普勒血流导丝测量中心主动脉压、冠状动脉内压和冠状动脉内多普勒血流速度。与主动脉压变化相似，EECP导致舒张压急剧升高(基线时71±10 mm Hg)至137±21 mm Hg;+93%， P <0.0001)，平均冠状动脉内压(88±9 ~ 102±16 mm Hg);+16%， P =0.006)，收缩压下降(116±20 ~ 99±26 mm Hg);−15%;P = 0.002)。冠状动脉内多普勒测量的平均峰值速度从基线时的11±5 cm/s增加到EECP期间的23±5 cm/s (+109%， P =0.001)。TIMI框架计数，冠状动脉血流的定量血管造影测量，显示与基线相比，EECP期间冠状动脉血流增加28% (P =0.001)。结论:eecp明确且显著地增加了中央主动脉和冠状动脉的舒张压和平均压，降低了收缩压。冠状动脉血流，由多普勒和血管造影技术确定，在EECP期间增加。收缩期卸荷和冠脉灌注压升高的联合作用证明EECP可能作为一种潜在的机械辅助装置。
{"title":"Left Ventricular Systolic Unloading and Augmentation of Intracoronary Pressure and Doppler Flow During Enhanced External Counterpulsation","authors":"A. Michaels, M. Accad, T. Ports, W. Grossman","doi":"10.1161/01.CIR.0000028336.95629.B0","DOIUrl":"https://doi.org/10.1161/01.CIR.0000028336.95629.B0","url":null,"abstract":"Background—Enhanced external counterpulsation (EECP) is a noninvasive, pneumatic technique that provides beneficial effects for patients with chronic, symptomatic angina pectoris. However, the physiological effects of EECP have not been studied directly. We examined intracoronary and left ventricular hemodynamics in the cardiac catheterization laboratory during EECP. Methods and Results—Ten patients referred for diagnostic evaluation underwent left heart catheterization and coronary angiography from the radial artery. At baseline and then during EECP, central aortic pressure, intracoronary pressure, and intracoronary Doppler flow velocity were measured using a coronary catheter, a sensor-tipped high-fidelity pressure guidewire, and a Doppler flow guidewire, respectively. Similar to changes in aortic pressure, EECP resulted in a dramatic increase in diastolic (71±10 mm Hg at baseline to 137±21 mm Hg during EECP; +93%;P <0.0001) and mean intracoronary pressures (88±9 to 102±16 mm Hg; +16%;P =0.006) with a decrease in systolic pressure (116±20 to 99±26 mm Hg; −15%;P =0.002). The intracoronary Doppler measure of average peak velocity increased from 11±5 cm/s at baseline to 23±5 cm/s during EECP (+109%;P =0.001). The TIMI frame count, a quantitative angiographic measure of coronary flow, showed a 28% increase in coronary flow during EECP compared with baseline (P =0.001). Conclusions—EECP unequivocally and significantly increases diastolic and mean pressures and reduces systolic pressure in the central aorta and the coronary artery. Coronary artery flow, determined by both Doppler and angiographic techniques, is increased during EECP. The combined effects of systolic unloading and increased coronary perfusion pressure provide evidence that EECP may serve as a potential mechanical assist device.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"27 1","pages":"1237-1242"},"PeriodicalIF":0.0,"publicationDate":"2002-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90779154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-03DOI: 10.1161/01.CIR.0000028463.74880.EA
A. Decensi, U. Omodei, C. Robertson, B. Bonanni, A. Guerrieri-Gonzaga, F. Ramazzotto, H. Johansson, S. Mora, M. Sandri, M. Cazzaniga, M. Franchi, S. Pecorelli
Background—The increase in C-reactive protein (CRP) during oral conjugated equine estrogen (CEE) may explain the initial excess of cardiovascular disease observed in clinical studies. Because the effect of transdermal estradiol (E2) on CRP is unclear, we compared CRP changes after 6 and 12 months of transdermal E2 and oral CEE in a randomized 2×2 retinoid-placebo trial. Methods and Results—A total of 189 postmenopausal women were randomized to 50 &mgr;g/d transdermal E2 and 100 mg BID of the retinoid fenretinide (n=45), 50 &mgr;g/d transdermal E2 and placebo (n=49), 0.625 mg/d oral CEE and 100 mg BID fenretinide (n=46), or 0.625 mg/d oral CEE and placebo (n=49) for 1 year. Sequential medroxyprogesterone acetate was added in each group. Relative to baseline, CRP increased by 10% (95% CI −9% to 33%) and by 48% (95% CI 22% to 78%) after 6 months of transdermal E2 and oral CEE, respectively. The corresponding figures at 12 months were 3% (95% CI −14% to 23%) for transdermal E2 and 64% (95% CI 38% to 96%) for oral CEE. Fenretinide did not change CRP levels at 6 and 12 months relative to placebo. Relative to oral CEE, the mean change in CRP after 12 months of transdermal E2 was −48% (95% CI −85% to −7%, P =0.012), whereas fenretinide was associated with a mean change of −1% (95% CI −34% to 40%, P =0.79) compared with placebo. Conclusions—In contrast to oral CEE, transdermal E2 does not elevate CRP levels up to 12 months of treatment. The implications for early risk of coronary heart disease require further studies.
背景:口服结合马雌激素(CEE)期间c反应蛋白(CRP)的增加可能解释了临床研究中观察到的心血管疾病的初始过量。由于透皮雌二醇(E2)对CRP的影响尚不清楚，我们在一项随机2×2类视黄酮-安慰剂试验中比较了透皮E2和口服CEE在6个月和12个月后CRP的变化。方法与结果:共有189名绝经后妇女被随机分为50 g/d透皮E2和100 mg BID的类维生素a芬维甲酸组(n=45)， 50 g/d透皮E2和安慰剂组(n=49)， 0.625 mg/d口服CEE和100 mg BID的芬维甲酸组(n=46)，或0.625 mg/d口服CEE和安慰剂组(n=49)，为期1年。各组依次添加醋酸甲孕酮。相对于基线，经皮E2和口服CEE 6个月后，CRP分别增加了10% (95% CI - 9%至33%)和48% (95% CI 22%至78%)。12个月时的相应数据为透皮E2为3% (95% CI - 14% - 23%)，口服CEE为64% (95% CI 38% - 96%)。与安慰剂相比，芬维啶在6个月和12个月时没有改变CRP水平。相对于口服CEE，经皮E2治疗12个月后CRP的平均变化为- 48% (95% CI - 85%至- 7%，P =0.012)，而与安慰剂相比，芬维啶的平均变化为- 1% (95% CI - 34%至40%，P =0.79)。结论:与口服CEE相比，透皮E2在治疗12个月后不会升高CRP水平。对冠心病早期风险的影响需要进一步研究。
{"title":"Effect of Transdermal Estradiol and Oral Conjugated Estrogen on C-Reactive Protein in Retinoid-Placebo Trial in Healthy Women","authors":"A. Decensi, U. Omodei, C. Robertson, B. Bonanni, A. Guerrieri-Gonzaga, F. Ramazzotto, H. Johansson, S. Mora, M. Sandri, M. Cazzaniga, M. Franchi, S. Pecorelli","doi":"10.1161/01.CIR.0000028463.74880.EA","DOIUrl":"https://doi.org/10.1161/01.CIR.0000028463.74880.EA","url":null,"abstract":"Background—The increase in C-reactive protein (CRP) during oral conjugated equine estrogen (CEE) may explain the initial excess of cardiovascular disease observed in clinical studies. Because the effect of transdermal estradiol (E2) on CRP is unclear, we compared CRP changes after 6 and 12 months of transdermal E2 and oral CEE in a randomized 2×2 retinoid-placebo trial. Methods and Results—A total of 189 postmenopausal women were randomized to 50 &mgr;g/d transdermal E2 and 100 mg BID of the retinoid fenretinide (n=45), 50 &mgr;g/d transdermal E2 and placebo (n=49), 0.625 mg/d oral CEE and 100 mg BID fenretinide (n=46), or 0.625 mg/d oral CEE and placebo (n=49) for 1 year. Sequential medroxyprogesterone acetate was added in each group. Relative to baseline, CRP increased by 10% (95% CI −9% to 33%) and by 48% (95% CI 22% to 78%) after 6 months of transdermal E2 and oral CEE, respectively. The corresponding figures at 12 months were 3% (95% CI −14% to 23%) for transdermal E2 and 64% (95% CI 38% to 96%) for oral CEE. Fenretinide did not change CRP levels at 6 and 12 months relative to placebo. Relative to oral CEE, the mean change in CRP after 12 months of transdermal E2 was −48% (95% CI −85% to −7%, P =0.012), whereas fenretinide was associated with a mean change of −1% (95% CI −34% to 40%, P =0.79) compared with placebo. Conclusions—In contrast to oral CEE, transdermal E2 does not elevate CRP levels up to 12 months of treatment. The implications for early risk of coronary heart disease require further studies.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"102 1","pages":"1224-1228"},"PeriodicalIF":0.0,"publicationDate":"2002-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90556889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-03DOI: 10.1161/01.CIR.0000027816.54430.96
T. Cyrus, Syuan Sung, Lei Zhao, C. Funk, Syun Tang, D. Praticò
Background—Atherosclerosis is a complex vascular inflammatory disease. Low-dose aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. We wished to determine the effect of low-dose aspirin on vascular inflammation, plaque composition, and atherogenesis in LDL receptor–deficient mice fed a high fat diet. Methods and Results—In LDL receptor–deficient mice fed a high fat diet compared with control mice, low-dose aspirin induced a significant decrease in circulating levels and vascular formation of soluble intercellular molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-&agr;, interleukin-12p 40, without affecting lipid levels. This was associated with significant reduction of the nuclear factor &kgr;B activity in the aorta. Low-dose aspirin also significantly reduced the extent of atherosclerosis. Finally, aortic vascular lesions of the aspirin-treated animals showed 57% reduction (P <0.05) in the amount of macrophage cells, 77% increase in smooth muscle cells (P <0.05), and 23% increase in collagen (P <0.05). Conclusions—Our results suggest that in murine atherosclerosis, low-dose aspirin suppresses vascular inflammation and increases the stability of atherosclerotic plaques, both of which, together with its antiplatelet activity, contribute to its antiatherogenic effect. We conclude that low-dose aspirin might be rationally evaluated in the progression and evolution of human atherosclerotic plaque.
{"title":"Effect of Low-Dose Aspirin on Vascular Inflammation, Plaque Stability, and Atherogenesis in Low-Density Lipoprotein Receptor–Deficient Mice","authors":"T. Cyrus, Syuan Sung, Lei Zhao, C. Funk, Syun Tang, D. Praticò","doi":"10.1161/01.CIR.0000027816.54430.96","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027816.54430.96","url":null,"abstract":"Background—Atherosclerosis is a complex vascular inflammatory disease. Low-dose aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. We wished to determine the effect of low-dose aspirin on vascular inflammation, plaque composition, and atherogenesis in LDL receptor–deficient mice fed a high fat diet. Methods and Results—In LDL receptor–deficient mice fed a high fat diet compared with control mice, low-dose aspirin induced a significant decrease in circulating levels and vascular formation of soluble intercellular molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-&agr;, interleukin-12p 40, without affecting lipid levels. This was associated with significant reduction of the nuclear factor &kgr;B activity in the aorta. Low-dose aspirin also significantly reduced the extent of atherosclerosis. Finally, aortic vascular lesions of the aspirin-treated animals showed 57% reduction (P <0.05) in the amount of macrophage cells, 77% increase in smooth muscle cells (P <0.05), and 23% increase in collagen (P <0.05). Conclusions—Our results suggest that in murine atherosclerosis, low-dose aspirin suppresses vascular inflammation and increases the stability of atherosclerotic plaques, both of which, together with its antiplatelet activity, contribute to its antiatherogenic effect. We conclude that low-dose aspirin might be rationally evaluated in the progression and evolution of human atherosclerotic plaque.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"88 1","pages":"1282-1287"},"PeriodicalIF":0.0,"publicationDate":"2002-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79601861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-09-03DOI: 10.1161/01.CIR.0000027821.55835.00
H. Oral, B. Knight, Mehmet Özaydın, A. Chugh, S. Lai, C. Scharf, S. Hassan, R. Greenstein, Jihn Han, F. Pelosi, S. Strickberger, F. Morady
Background—The purpose of this study was to determine the feasibility and mechanistic implications of segmental pulmonary vein (PV) ostial ablation during atrial fibrillation (AF). Methods and Results—Forty consecutive patients underwent PV isolation for AF. Among 125 PVs targeted for isolation, ablation was performed during AF in 70 veins and during sinus rhythm in 55 veins. A decapolar Lasso catheter was positioned near the ostium. During AF, ostial ablation was performed near the Lasso catheter electrodes that recorded a tachycardia with a cycle length shorter than in the adjacent left atrium. During sinus rhythm, ostial ablation was guided by PV potentials. Complete PV isolation was achieved in 70 PVs (100%) ablated during AF and in 53 PVs (96%) ablated during sinus rhythm (P =0.4). The mean durations of radiofrequency energy needed for isolation were 7.4±4.4 and 5.2±3.9 minutes during AF and sinus rhythm, respectively (P <0.01). Before ablation, an immediate recurrence of AF (IRAF), occurred after cardioversion in 18 of 40 patients, and IRAF was consistently abolished by PV isolation. The probability of AF termination during isolation of a PV was directly related to the extent of tachycardia in that vein. As more PVs were isolated, induction of persistent AF by rapid pacing became less likely. Conclusions—Segmental ostial ablation guided by PV tachycardia during AF is feasible and as efficacious as during sinus rhythm. The responses to cardioversion, ablation, and rapid pacing observed in this study imply that IRAF is triggered by the PVs and that PV tachycardias may play an important role in the perpetuation of AF.
{"title":"Segmental Ostial Ablation to Isolate the Pulmonary Veins During Atrial Fibrillation: Feasibility and Mechanistic Insights","authors":"H. Oral, B. Knight, Mehmet Özaydın, A. Chugh, S. Lai, C. Scharf, S. Hassan, R. Greenstein, Jihn Han, F. Pelosi, S. Strickberger, F. Morady","doi":"10.1161/01.CIR.0000027821.55835.00","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027821.55835.00","url":null,"abstract":"Background—The purpose of this study was to determine the feasibility and mechanistic implications of segmental pulmonary vein (PV) ostial ablation during atrial fibrillation (AF). Methods and Results—Forty consecutive patients underwent PV isolation for AF. Among 125 PVs targeted for isolation, ablation was performed during AF in 70 veins and during sinus rhythm in 55 veins. A decapolar Lasso catheter was positioned near the ostium. During AF, ostial ablation was performed near the Lasso catheter electrodes that recorded a tachycardia with a cycle length shorter than in the adjacent left atrium. During sinus rhythm, ostial ablation was guided by PV potentials. Complete PV isolation was achieved in 70 PVs (100%) ablated during AF and in 53 PVs (96%) ablated during sinus rhythm (P =0.4). The mean durations of radiofrequency energy needed for isolation were 7.4±4.4 and 5.2±3.9 minutes during AF and sinus rhythm, respectively (P <0.01). Before ablation, an immediate recurrence of AF (IRAF), occurred after cardioversion in 18 of 40 patients, and IRAF was consistently abolished by PV isolation. The probability of AF termination during isolation of a PV was directly related to the extent of tachycardia in that vein. As more PVs were isolated, induction of persistent AF by rapid pacing became less likely. Conclusions—Segmental ostial ablation guided by PV tachycardia during AF is feasible and as efficacious as during sinus rhythm. The responses to cardioversion, ablation, and rapid pacing observed in this study imply that IRAF is triggered by the PVs and that PV tachycardias may play an important role in the perpetuation of AF.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"36 1","pages":"1256-1262"},"PeriodicalIF":0.0,"publicationDate":"2002-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74472499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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