It has been shown that infusion of L-arginine into the brachial artery augments endothelium-dependent forearm vasodilation and reverses the defective endothelium-dependent vasodilation associated with an elevated plas...
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It has been shown that infusion of L-arginine into the brachial artery augments endothelium-dependent forearm vasodilation and reverses the defective endothelium-dependent vasodilation associated with an elevated plasma low-density lipoprotein level or hypercholesterolemia.1–3 L-arginine administration improves the coronary blood flow response to acetylcholine in patients with normal coronary arteries and hypercholesterolemia.3 It enhances nitric oxide generation and inhibits lesion formation after balloon angioplasty.4,5 A recent study showed vasodilation of coronary stenoses with intracoronary L-arginine, and another demonstrated that L-arginine improves flow-mediated dilation in hypercholesterolemic subjects and smokers, but not in diabetic subjects.6–8 In this study we therefore have investigated the impact of smoking and hypercholesterolemia on the vasomotor effects of L-arginine in epicardial coronary arteries in patients with stable angina and coronary artery disease.
Several studies have been undertaken using myocardial perfusion imaging to detect myocardial ischemia in patients with mitral valve prolapse (MVP).1–9 Controversial results were obtained in patients with MVP without ...
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Several studies have been undertaken using myocardial perfusion imaging to detect myocardial ischemia in patients with mitral valve prolapse (MVP).1–9 Controversial results were obtained in patients with MVP without coronary artery disease.1–11 Moreover, these previous studies have been performed mostly in the 1970s using planar myocardial perfusion imaging with thallium-201 (Tl-201).1–8 Recently, it was shown that single-photon emission computed tomography has better ability to allow visual analysis of all coronary regions in the diagnosis of coronary artery disease than planar imaging.12–14 This study was designed to assess myocardial perfusion imaging using single-photon emission computed tomographic (SPECT) analysis and recently established echocardiographic criteria for MVP.
OBJECTIVES This study focused on 1) the determination of the optimal preconditioning (PC) duration, and 2) the protective effect of nicorandil (NC), a hybrid nitrate with a KATP channel opening effect, during a percut...
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OBJECTIVES This study focused on 1) the determination of the optimal preconditioning (PC) duration, and 2) the protective effect of nicorandil (NC), a hybrid nitrate with a KATP channel opening effect, during a percutaneous transluminal coronary angioplasty (PTCA) model in humans. BACKGROUND The ischemic PC effect is induced in 180 s ischemia, but not in 120 s ischemia in rabbit hearts. However, the duration of ischemia that induces PC effect and the role of the KATP channel in the PC effect in humans are still unclear. METHODS Forty-six patients with stable angina were randomly allocated to four groups: the duration of the first inflation as PC ischemia was 60 s in the PC60 group (n = 12), and 180 s in the PC180 group (n = 12). In the other groups, NC (80 mu g/kg) was intravenously given for 1 min in the NC group (n = 12), and isosorbide dinitrate (ISDN) (40 mu g/kg) was given in the ISDN group (n = 10). Five minutes after first inflation or drug administration, a second inflation was conducted for 120 s in each group. In the EGG, the lead with the largest shift in ST segment (deltaST max), and the sum of elevated ST levels in all leads (sigmaST) were determined. RESULTS In the PC60 group, no significant difference was observed in either deltaST max or sigmaST between the first and second inflation. However;the second inflation in the PC180 group showed significantly lower levels of deltaST max and sigmaST compared with those of the first inflation. In the NC group, both deltaST max and sigmaST measured at 30 s and 60 s after balloon inflation were significantly lower than those of the first inflation in the PC60 and PC180 control groups. In the ISDN group, no significant difference was observed in deltaST max or sigmaST. CONCLUSION In human PTCA models, a PC effect is observed in 180 s ischemia, but not in 60 s ischemia. A pharmacological PC effect is induced by NC, a KATP channel opener with a nitrate-like effect but not ISDN. This suggests that the Opening of KA
Background The purpose of this study was to assess whether pharmacologic preconditioning by exogenous or endogenous adenosine prevents the deterioration of hemodynamic function and left ventricular performance during ...
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Background The purpose of this study was to assess whether pharmacologic preconditioning by exogenous or endogenous adenosine prevents the deterioration of hemodynamic function and left ventricular performance during percutaneous transluminal coronary angioplasty (PTCA). Ischemic preconditioning renders the heart more resistant to subsequent ischemia. Adenosine plays a key role in its pathogenesis. Coronary angioplasty is a suitable model for the induction of myocardial ischemia. Methods and Results We investigated 30 patients receiving PTCA of the left anterior descending coronary. Patients were randomly allocated to either dipyridamole, leading to the liberation of endogenous adenosine (0.5 mg/kg body weight, intracoronary), exogenous adenosine (20 mg intracoronary), or an equal amount of saline. Chest pain, tolerated inflation time, and ST-segment shift were registered. Left ventricular hemodynamics, isovolumetric phase indexes, indexes of volume, election fraction, and indexes of diastolic dysfunction were analyzed. Patients receiving endogenous or exogenous adenosine tolerated longer balloon inflation times (dipyridamole, 208 +/- 23 seconds;adenosine, 188 +/- 41 seconds;control, 153 +/- 36 seconds;P < .05). Deterioration of left ventricular ejection fraction was less severe after adenosine (72% +/- 5% before PTCA vs 64% +/- 6% during angioplasty;P = .11) and could be prevented by intracoronary dipyridamole (69% +/- 12% before PTCA vs 68% +/- 11% after PTCA;P < .01) compared with the control group (71% +/- 7% before PTCA vs 60% +/- 7% during angioplasty). Conclusions Intracoronary application of exogenous adenosine and liberation of endogenous adenosine increase the tolerance to ischemia and prevent deterioration of left ventricular function during ischemia. These findings can be attributed to ischemic preconditioning. However, endogenous adenosine exceeds the protective effects of exogenous adenosine.
OBJECTIVES The study evaluated whether heavy exposure to environmental tobacco smoke (passive smoking) might damage arterial function in modernized Chinese. BACKGROUND Heavy passive smoking is associated With arterial...
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OBJECTIVES The study evaluated whether heavy exposure to environmental tobacco smoke (passive smoking) might damage arterial function in modernized Chinese. BACKGROUND Heavy passive smoking is associated With arterial endothelial dysfunction in Caucasian, but not rural Chinese, subjects. METHODS We studied 20 young (mean age 36.6 +/- 7.0 years) nonsmoking asymptomatic casino workers (9 men) in Macau who were exposed to environmental tobacco smoke for over 8 h/day for at least two years and 20 normal subjects (control subjects). These two groups were carefully matched for age, gender, body mass index (BMI), blood pressure, vessel diameter, cholesterol and glucose levels. Brachial artery diameter was measured by high-resolution B-mode ultrasound at rest, after flow increase (causing flow-mediated endothelium-dependent dilation) and after sublingual nitroglycerin tan endothelium-independent dilator). RESULTS Flow-mediated dilation (mean +/- SD% of diameter changes) was significantly lower in passive smokers (6.6 +/- 3.4%) compared with the controls (10.6 +/- 2.3%) (p < 0.0001). Nitroglycerin-induced dilation of the two groups were similar. Upon multivariate analysis, passive smoking exposure was the strongest independent predictor (beta = -0.59;p = 0.0001) for impaired flow-mediated endothelium-dependent dilation (model R-2 = 0.75, F value = 6.1, p = 0.0001). CONCLUSIONS In modernized Chinese, as in Caucasians, exposure to heavy environmental tobacco smoke causes arterial endothelial dysfunction, a key early event in atherosclerosis. This may have serious implications for cardiovascular health in China, currently in a process of rapid modernization. CT Am Cell Cardiol 2000;36:1228-32) (C) 2000 by the American College of Cardiology.
Background. Diltiazem is widely used to prevent radial artery spasm after coronary bypass grafting (CABG). However, recent in vitro and in vivo studies have shown that nitroglycerin is a superior conduit vasodilator c...
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Background. Diltiazem is widely used to prevent radial artery spasm after coronary bypass grafting (CABG). However, recent in vitro and in vivo studies have shown that nitroglycerin is a superior conduit vasodilator compared to diltiazem. A clinical comparison of these agents in patients undergoing CABG has not been previously performed. Methods. One hundred sixty-one consecutive patients undergoing isolated CABG with the radial artery were prospectively randomized to 24-hour intravenous infusion of nitroglycerin or diltiazem followed by 6-month treatment with a daily dose of isosorbide mononitrate (n = 84) or diltiazem CD (n = 77). Analyses were performed on "intention-to-treat" basis. Results. Crossovers because of low cardiac output, complete heart block, or sinus bradycardia occurred in 5 patients in the diltiazem group and none in the nitroglycerin group (p = 0.05). Operative mortality (nitroglycerin, 1.2% versus diltiazem, 1.3%), major morbidity (14% versus 16%), perioperative myocardial infarction (1.2% versus 0%), peak serum creatinine phosphokinase MB fraction levels (27 versus 21 U), intensive care unit stay (34 +/- 19 versus 38 +/- 30 hours) and total hospital length of stay (4.7 +/- 1.4 versus 4.7 +/- 1.3 days) were similar (p = not significant for all). Cardiac pacing was required more often in the diltiazem group (28% versus 13%, p = 0.01). Follow-up longer than 2 months was available in 145 patients (90%). Follow-up mortality (nitroglycerin, 1.2%;diltiazem, 1.3%), myocardial infarction (6%, versus 5%), and reintervention (8% versus 6%) rates and average angina class (1.3 +/- 0.7 versus 1.1 +/- 0.4) were similar (p = not significant for all). Thallium stress test obtained in 117 patients showed abnormal perfusion in the radial artery territory in only 4 patients (3%), 2 in each group (P = not significant). Treatment with diltiazem was more costly ($16,340 versus $1,096). Conclusions. Nitroglycerin is preferable to diltiazem for prevention of conduit sp
PURPOSE: We performed a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the relative efficacy and safety of cilostazol and pentoxifylline. PATIENTS AND METHODS: We enrolled patients with mo...
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PURPOSE: We performed a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the relative efficacy and safety of cilostazol and pentoxifylline. PATIENTS AND METHODS: We enrolled patients with moderate-to-severe claudication from 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university medical centers in the United States. Of 922 consenting patients, 698 met the inclusion criteria and were randomly assigned to blinded treatment with either cilostazol (100 mg orally twice a day), pentoxifylline (400 mg orally 3 times a day), or placebo. We measured maximal walking distance with constant-speed, variable-grade treadmill testing at baseline and at 4, 8, 12, 16, 20, and 24 weeks. RESULTS: Mean maximal walking distance of cilostazol-treated patients (n = 227) was significantly greater at every postbaseline visit compared with patients who received pentoxifylline (n = 232) or placebo (n = 239). After 24 weeks of treatment, mean maximal walking distance increased by a mean of 107 m (a mean percent increase of 54% from baseline) in the cilostazol group, significantly more than the 64-m improvement (a 30% mean percent increase) with pentoxifylline (P <0.001). The improvement with pentoxifylline was similar (P = 0.82) to that in the placebo group (65 m, a 34% mean percent increase). Deaths and serious adverse event rates were similar in each group. Side effects (including headache, palpitations, and diarrhea) were more common in the cilostazol-treated patients, but withdrawal rates were similar in the cilostazol (16%) and pentoxifylline (19%) groups. CONCLUSION: Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances in patients with intermittent claudication, but was associated with a greater frequency of minor side effects. Pentoxifylline and placebo had similar effects. Am J Med. 2000;109:523-530. (C) 2000 by Excerpta Medica, Inc.
OBJECTIVES The present study evaluates the impact of total cholesterol (TC) and its subfractions on coronary flow reserve (CFR), an index of the integrated function of the coronary circulation, in asymptomatic subject...
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OBJECTIVES The present study evaluates the impact of total cholesterol (TC) and its subfractions on coronary flow reserve (CFR), an index of the integrated function of the coronary circulation, in asymptomatic subjects. BACKGROUND Endothelial dysfunction of the coronary microcirculation has been reported in asymptomatic subjects with hypercholesterolemia. METHODS Using oxygen-15-labeled water and positron emission tomography, myocardial blood flow (MBF, in ml/min per g) was measured at rest and during intravenous adenosine (140 mu g/kg body weight per min) in 80 asymptomatic nonsmoking men: group 1 (n = 61;age 45 +/- 7 years) had normal TC (less than or equal to 6.5 mmol/liter or less than or equal to 250 mg/dl) and group 2 (n = 19;age 48 +/- 10 years) had elevated TC. RESULTS Total cholesterol were 5.1 +/- 0.8 and 7.2 +/- 0.7 mmol/liter in groups 1 and 2 (p < 0.0005), respectively;low density lipoprotein (LDL) cholesterol levels were 3.2 +/- 0.8 and 4.9 +/- 0.7 mmol/liter (p < 0.0005);high density lipoprotein (HDL) cholesterol levels were 1.1 +/- 0.3 and 1.0 +/- 0.4 mmol/liter (p = NS);and triglyceride levels were 1.8 +/- 1.3 and 3.0 +/- 1.8 mmol/liter (p < 0.005). Groups 1 and 2 did not differ with regard to MBF at rest (0.87 +/- 0.14 vs. 0.84 +/- 0.14), MBF during adenosine (3.63 +/- 1.02 vs. 3.30 +/- 0.86) or CFR (4.23 +/- 1.29 vs. 3.95 +/- 0.93). A significant but weak correlation was found between CFR and HDL in group 1 (r = 0.29, p < 0.05), but not in group 2. In contrast, a significant inverse correlation between LDL and CFR was found in group 2 (r = -0.61, p < 0.05), but not in group 1. CONCLUSION Low density lipoprotein cholesterol but not TC correlated inversely with CFR in hypercholesterolemic subjects. Thus, LDL-induced coronary microvascular dysfunction could play an important role in the pathogenesis of coronary artery disease and its complications. (J Am Coil Cardiol 2000;36:103-9) (C) 2000 by the American College of Cardiology.
OBJECTIVES The aim of this study was to assess whether endogenous accumulation of adenosine, induced by low-dose dipyridamole infusion, protects from exercise-induced ischemia. BACKGROUND Adenosine is a recognized med...
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OBJECTIVES The aim of this study was to assess whether endogenous accumulation of adenosine, induced by low-dose dipyridamole infusion, protects from exercise-induced ischemia. BACKGROUND Adenosine is a recognized mediator of ischemic preconditioning in experimental settings. METHODS Ten patients (all men: mean age 63.4 +/- 7.3 years) with chronic stable angina, angiographically assessed coronary artery disease (n = 7) or previous myocardial infarction (n = 3) and exercise-induced ischemia underwent on different days two exercise-stress echo tests after premedication with placebo or dipyridamole (15 mg in 30 min, stopped 5 min before testing) in a double-blind, placebo controlled, randomized crossover design. RESULTS In comparison with placebo, dipyridamole less frequently induced chest pain (20% vs. 100%, p = 0.001) and >0.1 mV ST segment depression (50% vs. 100%, p < 0.05). Wall motion abnormalities during exercise-stress test were less frequent (placebo = 100% vs. dipyridamole = 70%, p = ns) and significantly less severe (wall motion score index at peak stress: placebo = 1.55 +/- 0.17 vs, dipyridamole = 1.27 +/- 0.2, p < 0.01) following dipyridamole, which also determined an increase in exercise time up to echocardiographic positivity (placebo = 385.9 +/- 51.4 vs. dipyridamole = 594.4 +/- 156.9 s, p < 0.01). CONCLUSIONS Low-dose dipyridamole infusion increases exercise tolerance in chronic stable angina, possibly by endogenous adenosine accumulation acting on high affinity Al myocardial receptors involved in preconditioning or positively modulating coronary flow through collaterals. (C) 1999 by the American College of Cardiology.
OBJECTIVES The aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium dependent vasodilation in patients with chronic heart failure (...
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OBJECTIVES The aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium dependent vasodilation in patients with chronic heart failure (CHF). BACKGROUND Endothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg. and regular physical exercise. METHODS Forty patients with severe CHF (left ventricular ejection fraction 19 +/- 9%) were randomized to an L-arg. group (8 g/day), a training group (T) with daily handgrip training, L-arg, and T (L-arg. + T) or an inactive control group (C). The mean internal radial artery diameter was determined at the beginning and after four weeks in response to brachial arterial administration of acetylcholine (ACh) (7.5, 15, 30 mu g/min) and nitroglycerin (0.2 mg/min) with a transcutaneous high-resolution 10 MHz A-mode echo tracking system coupled with a Doppler device. The power of the study to detect clinically significant differences in endothelium-dependent vasodilation was 96.6%. RESULTS At the beginning, the mean endothelium-dependent vasodilation in response to ACh, 30 mu g/min was 2.54 +/- 0.09% (p = NS between groups). After four weeks, internal radial artery diameter increased by 8.8 +/- 0.9% after ACh 30 mu g/min in L-arg. (p < 0.001 vs. C), by 8.6 +/- 0.9% in T (p < 0.001 vs. C) and by 12.0 +/- 0.3% in L-arg, + T (p < 0.005 vs. C, L-arg. and T). Endothelium independent vasodilation as assessed by infusion of nitroglycerin was similar in all groups at the beginning and at the end of the study. CONCLUSIONS Dietary supplementation of L-arg. as well as regular physical exercise improved agonist-mediated, endothelium-dependent vasodilation to a similar extent. Both interventions together seem to produce additive effects with respect to endothelium-dependent vasodilation. (C) 2000 by the American College of Cardiology.
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