Effects of oral L-arginine supplementation on exercise-induced QT dispersion and exercise tolerance in stable angina pectoris

We assessed the effects of L-arginine (an endogenous precursor of nitric oxide) on the magnitude of exercise-induced QT dispersion in patients with coronary artery disease. The study had a randomized double-blind cross-over design. Twenty-five patients with stable coronary artery disease underwent two separate exercise tests: after oral administration of L-arginine (6 g/24 h for 3 days) or placebo. Indications for cessation of exercise included: pulse limit, exhaustion, chest pain, ST segment depression >2 mm. We found that arginine significantly increased exercise duration from 604+/-146 to 647+/-159 s (P<0.03). However, it had no effect on the sum of exercise-induced ST segment depressions (1.9+/-2.3 and 2.4+/-3.3 on and off arginine, respectively, NS). Exercise shortened QT interval to a similar extent in patients treated with placebo or arginine. QT dispersion changed during exercise from 55+/-21 to 60+/-19 ms (NS) and from 60+/-21 to 53+/-17 ms (NS), respectively. We conclude that, in patients with coronary artery disease, oral supplementation of L-arginine does not affect exercise-induced changes in QT interval duration, QT dispersion or the magnitude of ST segment depression. However, it significantly increases exercise tolerance, most likely due to improved peripheral vasomotion. These results may be of clinical and therapeutic importance.     

Effect of atorvastatin on exercise-induced myocardial ischemia in patients with stable angina pectoris

To investigate whether marked and sustained lipid-lowering in subjects with stable angina pectoris and dyslipidemia reduces exercise-induced myocardial ischemia, 17 subjects were treated with dose-adjusted atorvastatin over 1 year and underwent serial evaluation of exercise electrocardiographic ischemic parameters, serum biomarkers, and brachial artery endothelial function. Endothelial function improved progressively and C-reactive protein, P-selectin, and tissue plasminogen activator inhibitor levels decreased, but there was no decrease in exercise electrocardiographic ischemia.     

Effects of L-carnitine on exercise tolerance in patients with stable angina pectoris

The effects of L-carnitine (900 mg, p.o. daily) on exercise performance were studied in 12 patients with stable effort angina using a multistage treadmill exercise test. Exercise tests were performed at the end of the placebo period and after 4 and 12 weeks of carnitine therapy. While 12 patients experienced angina during treadmill tests in the placebo period, 2 patients were free of angina after treatment with carnitine. The mean exercise time was 11.4 +/- 0.7 min (mean +/- SE) in the placebo period. This increased significantly to 12.2 +/- 0.5 min (p less than 0.05) after 4 weeks and 12.8 +/- 0.5 min (p less than 0.01) after 12 weeks of treatment with carnitine. The time required for 1 mm ST depression to occur was 6.4 +/- 0.9 min in the placebo period. This increased significantly to 7.6 +/- 0.9 min (p less than 0.01) after 4 weeks and 8.8 +/- 1.0 min after 12 weeks of treatment with carnitine. There was significantly less ST segment depression during the same exercise load after 12 weeks of treatment as compared with that in the placebo period (p less than 0.05). The heart rate and the pressure rate product at the same work load showed no significant difference among the 3 testing periods. The results of this study suggest that L-carnitine may improve exercise tolerance in patients with effort angina.     

Dissociation of exercise tolerance and total myocardial ischemic burden in chronic stable angina pectoris

Exercise treadmill tests and ambulatory monitoring were used in a double-blind, placebo-controlled, double-dummy crossover comparison of nifedipine (10 mg, 3 times daily) and transdermal nitroglycerin (15 mg). All patients (n = 20) had chronic stable angina with symptomatic and silent events. All patients had 3 episodes of angina/week and 3 episodes of ischemia/24 hr. The protocol was made up of 2 weeks of placebo followed by 2 weeks of active drug, then crossed over for 2 weeks of placebo followed by the other active drug. At the end of each 2-week period, patients had ambulatory monitoring and exercise treadmill testing. All ambulatory monitoring reports were read blind and entered into an independent data base. The results were the following: on transdermal nitroglycerin, the duration of ischemia decreased by 57% from 140 min/24 hr to 60 min/24 hr (p = 0.0054). The exercise time increased by 5.5% from 4.8 to 5.0 minutes (p = 0.16). With nifedipine, the duration of ischemia decreased by 22% from 175 min/24 hr to 137 min/24 hr (p = 0.16). The exercise tolerance time increased by 13% from 4.5 to 5.0 minutes (p = 0.0264). Nifedipine increased exercise time without altering total ischemic time, while transdermal nitroglycerin decreased total ischemic time without increasing exercise time. Thus, changes in exercise time do not necessarily predict changes in total ischemic time.     

ST-segment fluctuation during treadmill exercise in patients with angina pectoris

The level of the ST-segment fluctuates transiently during treadmill exercise in some patients with angina pectoris. In the present study, the incidence and clinical significance of ST-segment fluctuation were studied before and after propranolol in 52 patients with angina pectoris. A transient greater than 0.5-mm (0.05 mV) upward shift of the ST-segment during a graded treadmill test was considered a significant fluctuation in leads without signs of previous myocardial infarction. The fluctuation was observed in three of 30 patients with rest or rest and effort angina pectoris before propranolol and in 14 of them after propranolol, while only one of 22 patients with effort angina alone showed fluctuation after the drug. Coronary arteriography revealed that in 15 patients showing ST-segment fluctuation with propranolol, seven patients had no significant coronary stenosis, six had one-vessel disease and two had two-vessel disease. In 24 patients with documented coronary artery spasm, ST-segment fluctuation was induced in two (8%) before propranolol and in 13 (54%) after propranolol. Our results suggest that ST-segment fluctuation during graded treadmill exercise may be related to transient coronary vasospasms exacerbated by propranolol.     

Mechanisms of exercise-induced ST-segment depression in patients without typical angina pectoris

OBJECTIVE: To evaluate if exercise-induced ST-segment depression without typical angina pectoris is related to increases in sympatho-adrenal activity or beta-adrenoceptor sensitivity. PATIENTS: Thirteen patients (four men) aged 35-62 years with ST-segment depression during exercise but atypical symptoms and normal myocardial scintigraphy, and 13 matched controls. DESIGN AND INTERVENTIONS: Patients and controls were compared regarding responses with: (i) exercise testing without treatment, (ii) exercise testing following beta-adrenoceptor blockade by propranolol (0.15 mg kg(-1) i.v.), (iii) incremental adrenaline infusions (0.1, 0.2, 0.4 and 0.8 nmol kg(-1) min(-1)) and (iv) adrenaline infusions during alpha-adrenoceptor blockade by phentolamine (0.5 mg min(-1)). MAIN OUTCOME MEASURES: ST-segment depression and tissue Doppler parameters reflecting contractility. RESULTS: Exercise lowered the ST-segment by 2.44 mm without and 0.87 mm with beta-adrenoceptor blockade (P < 0.001 for difference) amongst patients, but not amongst controls. Maximal heart rate was slightly higher amongst patients (P < 0.05), despite similar loads and plasma catecholamine responses to exercise in the two groups; this difference disappeared after beta-adrenoceptor blockade with propranolol. ST-segment depression during adrenaline infusion was greater in patients compared with controls (P < 0.01) despite similar increases in heart rate. alpha-Blockade enhanced the ST-segment depression (P < 0.001) and heart rate (P < 0.001) responses to adrenaline infusion more markedly amongst patients. Tissue Doppler imaging showed similar contractility and diastolic relaxation responses of patients and controls to adrenaline, but early diastolic movements did not increase amongst patients after phentolamine (P < 0.01). CONCLUSIONS: Exercise-induced ST-segment depression in patients with a low likelihood of ischaemic heart disease is related to increased beta-adrenergic sensitivity regarding chronotropic and electrophysiological, but not inotropic responses.     

Effects of nifedipine on myocardial perfusion during exercise in chronic stable angina pectoris

Nifedipine may be effective in the treatment of stable angina by both decreasing myocardial oxygen demand and increasing myocardial oxygen supply. To determine the mechanism of action of nifedipine and its dose-response relation, 14 patients with stable angina were treated with nifedipine 10, 20 and 30 mg 4 times daily as single-agent therapy in a double-blind, randomized, placebo-controlled crossover trial. Treatment was continued for 1 week on each dose regimen and efficacy was determined using an exercise test at the end of each phase. Compared to placebo, a significant decrease of systolic blood pressure at peak exercise occurred with the nifedipine 20- and 30-mg regimens (p less than 0.05), accompanied by an increase in heart rate on the 10- and 20-mg regimens (p less than 0.005). There was no significant effect on the rate-pressure product compared to placebo at any exercise time on any of the nifedipine regimens. The times to onset of ST-segment depression and to angina were delayed significantly by all 3 dose regimens compared to placebo (p less than 0.02). There was a significant decrease in the magnitude of ST-segment depression at all exercise times by all dosage schedules of nifedipine compared with placebo (p less than 0.05), although there were no significant differences among the 3 dosage schedules. Data indicate that since nifedipine was effective in improving manifestations of myocardial ischemia during exercise without altering the double product at submaximal or maximal exercise, its beneficial mechanism of action may have been due to enhancing blood flow to ischemic zones or to favorably altering determinants of myocardial oxygen demand, which were not measured.     

卡尼汀与曲美他嗪对稳定型劳力性心绞痛患者运动耐量的影响

目的　比较卡尼汀与曲美他嗪对稳定型劳力性心绞痛患者临床疗效及运动耐量的影响。方法　选择 6 0例经冠状动脉造影确诊冠心病稳定型心绞痛伴高脂血症患者 ,经随机分为两组 ,分别予卡尼汀及曲美他嗪治疗 12W ,比较平均每周心绞痛发作次数 ,每周硝酸甘油消耗量 ,平板运动试验检测运动耐量及血脂水平。结果　卡尼汀及曲美他嗪均使心绞痛发作次数、硝酸甘油消耗量明显减少(P <0 0 1) ,运动至出现ST段压低 1mm所需时间、运动至出现心绞痛所需时间、运动诱发ST段缺血型下移之和∑ST明显减少 ,运动持续时间显著延长 (P <0 0 5 ) ,卡尼汀还降低总胆固醇、甘油三酯分别为 17%和 15 % ,高密度脂蛋白升高14 % (P <0 0 5 )。结论　卡尼汀及曲美他嗪均有效缓减稳定型心绞痛患者临床症状 ,改善运动诱发的心肌缺血 ,提高运动耐量 ,疗效相同 ,卡尼汀还改善血脂。     

Clinical significance of exercise-induced ST-segment elevation in lead aVR and V1 in patients with chronic stable angina pectoris and strongly positive exercise test results

Electrocardiographic abnormalities in lead aVR and V1 are rarely analyzed on exercise electrocardiograms. Clinical significance of exercise-induced ST-segment changes in lead aVR and V1 during strongly positive electrocardiographic exercise test (EET) in patients with chronic stable angina pectoris remains unclear. The aim of the study was to assess the value of lead aVR and V1 on the exercise electrocardiogram for the detection of left main coronary artery stenosis (LMCAS) and its equivalent (LMCASE) in patients with chronic stable angina pectoris and the strongly positive EET result. The study group consisted of 118 consecutive patients (mean age 58.8 +/- 9.5 years, range 38-77 years), including 30 (25.4%) women. Patients were divided into three groups. In group I, 31 patients with ST elevation in lead aVR and V1, in group II 66 patients with isolated ST elevation in lead aVR, and in group III 21 patients without ST elevation in lead aVR, induced with exercise, were included. Coronary arteriography results were compared among these groups. In patients with isolated exercise-induced ST elevation in lead aVR, the prevalence of LMCAS was five times more frequent than in patients without lead aVR ST elevation (25.8% vs 4.8% p<0.05). There were no differences in the prevalence of LMCASE and multi-vessel coronary disease in the studied groups. In patients with LMCAS significant ST elevation in lead aVR during strongly positive EET were observed (0.25 +/- 0,4 mm vs 1.43 +/- 0.6 mm p = 0.003), whereas there were no significant exercise-induced electrocardiographic changes in lead V1 (0.61 +/- 0.6 mm vs 0.77 +/- 0.6 mm p = 0.08). Sensitivity of isolated exercise-induced ST elevation in lead aVR in detection of LMCAS was 85.0%, specificity - 50.0%, positive predictive value - 25.8%, negative predictive value - 94.2%, and total accuracy - 55.9%. Exercise-induced ST elevation in lead aVR on the strongly positive exercise ECG may detect LMCAS in patients with chronic stable angina pectoris.     

运动训练对老年稳定型心绞痛患者运动耐量的影响

目的 探讨运动训练对老年稳定型心绞痛患者运动耐量的影响. 方法 60例老年稳定型心绞痛患者随机分为运动训练组(n=30)和常规治疗组(n=30),同时接受12周相同的冠心病药物治疗,运动训练组同时给予运动训练.用平板运动试验和6 min步行试验评估运动耐量. 结果 6 min步行距离与平板运动代谢当量显著相关(r＝0.816,P＜0.01);运动训练组和常规治疗组6 min步行距离较治疗前明显延长(P＜0.01或P＜0.05),运动训练组较常规治疗组延长更明显,差异有显著性(P＜0.05). 结论 运动训练能显著提高稳定型心绞痛患者的运动耐量,6 min步行试验可用来评估稳定型心绞痛患者的运动耐量.     

Exercise capacity with transdermal nitroglycerin in patients with stable angina pectoris

Transdermally delivered nitroglycerin (TTS-NTG) through a rate-controlling membrane yields stable blood levels for 24 h. We studied the effect of TTS-NTG (25 mg per 10 cm2) on exercise induced angina in 10 patients with stable angina pectoris, all in NYHA class III, who were not under treatment with other cardiac drugs. In a pre-study exercise test, all patients had angina pectoris and more than one mm ST depression. The study was placebo controlled and double blind with a randomized cross-over. Exercise tests were carried out on a treadmill according to the Bruce-protocol, 12 to 16 h after administration of TTS-NTG or of an identical placebo. After a 48 h wash-out period, the procedure was repeated after application of a plaster with the alternative content. A significant improvement was seen on TTS nitroglycerin compared with placebo in the total duration of exercise (7.2 +/- 3.6 min (mean +/- SD) vs 6.2 +/- 3.8 min; P less than 0.002). In 7 patients, the time to onset of angina was extended by TTS nitroglycerin. Maximal ST depression (lead V4 and V6) was significantly lower on TTS nitroglycerin (1.85 +/- 1 mm) compared with placebo (2.2 +/- 1 mm; P less than 0.05). It is concluded that 12 to 16 h after administration, transdermally delivered nitroglycerin improves exercise capacity and reduces maximal ST depression in patients with stable angina.     

Effects of iloprost, a stable prostacyclin analog, on exercise capacity and platelet aggregation in stable angina pectoris

The effects of iloprost, a chemically stable compound with prostacyclin mimetic activity, on exercise capacity and platelet aggregation were assessed in 24 patients with effort angina and proved critical (at least 70% diameter narrowing) coronary artery disease. Upright bicycle ergometer testing (25-W increments every 2 minutes) was performed during drug and placebo infusions using a crossover, randomized, single-blind protocol. Samples for measurements of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma were obtained in all patients before and during the study. Compared with placebo, intravenous iloprost consistently (p less than 0.001) prolonged exercise duration and time to onset of significant (0.1 mV) ST depression. Angina and ST depression occurred at a greater heart rate and rate-pressure product. Benefits were remarkable in some patients (67%) and not in others. Iloprost administration resulted in reduced platelet aggregation at peak exercise in all patients, whether they had consistent or little response to the drug. Thus, iloprost administration may improve exercise capacity in patients with stable exertional angina pectoris. Improvements are independent of changes in the major determinants of myocardial oxygen demand and associated with markedly reduced platelet aggregation, which may account for increased myocardial perfusion in patients with high sensitivity to coronary constriction.     

Asymptomatic myocardial ischemia in patients with stable and typical angina pectoris

The existence of transient myocardial ischemia (TMI) and the value of the serial dynamic electrocardiogram (DCG) in patients with variant or unstable angina pectoris are known. However, less information is available on the frequency and characteristics of TMI in patients with stable angina pectoris. For this study, we selected 40 patients with stable and typical angina pectoris. The presence of coronary artery disease and the ejection fraction were evaluated by means of angiocardiography. The DCG monitoring was performed with bichannel portable recorders for three 24-h periods at 7-day intervals. The patients were on optimal doses of beta blockers and isosorbidilate throughout the study. We detected 788 episodes of TMI in 22 of the 40 patients. The ejection fraction was poorer in the 22 patients with ST-T changes than in the 18 without such changes. The repolarization changes were: (1) ST elevation (55 symptomatic and 87 asymptomatic episodes, (2) ST depression (138 symptomatic and 236 asymptomatic episodes, and (3) T-wave changes (83 symptomatic and 164 asymptomatic episodes). All 22 patients with TMI presented a combination of the above changes. It appears, therefore, that ST-T changes are more frequent in patients with stable angina pectoris than was hitherto suspected. The DCG is valuable in assessing these changes, especially when one considers that the asymptomatic episodes are almost twice as frequent as the symptomatic ones. The asymptomatic episodes lasted a mean of 1.8±1.3 min (mean±SD), while the symptomatic episodes lasted 3.8±2.7 min (p <0.02, by sign test). Heart rate was unchanged during the episodes of TMI, and did not show any significant difference between asymptomatic and symptomatic episodes. Additional investigation is necessary, however, to determine the clinical implications of these findings.     

曲美他嗪对冠心病稳定性劳力型心绞痛患者心肌缺血的影响

目的探讨曲美他嗪对冠心病(CHD)稳定性劳力型心绞痛患者心肌缺血的影响.方法选择在1周内经2次运动试验结果为阳性,且运动持续时间变异低于10%的CHD稳定性劳力型心绞痛患者40例,在原有治疗不变的情况下,加用曲美他唪20mg每日3次,治疗12周.治疗前后均行平板运动试验,观察用药前后下述指标的变化(1)用药前后每周心绞痛发作的次数;(2)每周硝酸甘油片的用量;(3)心率及心率与收缩压的乘积;(4)运动诱发心绞痛发作所需的时间;(5)运动后ST段下降limn所需的时间;(6)运动持续时间;(7)总工作量.结果曲美他嗪应用12周后,患者每周心绞痛发作次数及硝酸甘油片的用量明显下降(P＜0.05),而对心率及心率与收缩压的乘积的影响无统计学显著意义(P＞0.05).与试验前相比,运动耐量和总工作量显著提高(P＜0.01),至心绞痛发作的时间及ST段下降1mm所需的时间均明显延长(P＜0.01).不良反应较少.结论曲美他嗪能增加CHD稳定性劳力型心绞痛患者的运动耐量,改善运动诱发心绞痛的心肌缺血,且安全有效,易于耐受.     

曲美他嗪对稳定型劳力性心绞痛患者 心肌缺血的影响

目的探讨曲美他嗪对冠心病(CHD)稳定型劳力性心绞痛患者心肌缺血的影响。方法选择经冠状动脉造影确诊的CHD稳定型劳力性心绞痛患者14例,在原有治疗不变的情况下,加用曲美他嗪治疗12周,治疗前后均行平板运动试验,观察用药前后下述指标的变化①用药前后每周心绞痛发作的次数;②每周硝酸甘油片的用量;③心率及心率和收缩压的乘积;④运动诱发心绞痛发作所需的时间;⑤运动后ST段下降0.1mV所需的时间;⑥运动持续时间。结果患者每周心绞痛发作的次数及硝酸甘油片的用量均明显下降(P＜0.05);心率及心率和收缩压乘积轻度变化(P＞0.05);明显延长运动诱发心绞痛所需的时间及运动后ST段下降≥0.1mV所需的时间(P＜0.05)。结论曲美他嗪能改善运动诱发的心肌缺血,对CHD劳力性心绞痛患者有一定的疗效。     

左旋卡尼汀能有效提高稳定型心绞痛患者的运动耐量

目的观察国产左旋卡尼汀（L-CN）对稳定型心绞痛患者临床症状和运动耐量的影响。方法在常规治疗的基础上使用L-CN辅助治疗稳定型心绞痛患者80例,40例患者作为对照。记录两组患者治疗前后临床症状、心电图、心功能、运动试验心电图。结果L-CN可以明显缓解患者心绞痛临床症状,改善心功能,并显著提高运动耐量和心绞痛负荷阈值。结论L-CN是心绞痛代谢治疗的有效药物之一。     

Failure of transdermal nitroglycerin to improve exercise capacity in patients with angina pectoris

Sixteen patients with stable angina pectoris were studied in a double blind crossover manner utilizing treadmill exercise testing with the direct measurement of total body oxygen uptake, 1 and 24 hours after application of a 20 cm2 transdermal nitroglycerin system and identical placebo. Testing was performed after a 3 day lead-in period of treatment with either an active patch or placebo. Points of analysis were peak angina and the submaximal work load occurring at 4 minutes of exercise. No statistically significant differences were observed between nitroglycerin and placebo treatment in any of the rest hemodynamic or peak angina variables at 1 or 24 hours. A significant increase in the rate-pressure product at the submaximal work load was observed 1 hour after transdermal nitroglycerin relative to placebo application. However, no significant differences were observed in any of the other measured variables at the submaximal work load, 1 or 24 hours after nitroglycerin application. The once daily application of a 20 cm2 transdermal nitroglycerin system was ineffective in altering the exercise capacity of patients with angina pectoris. The lack of efficacy at 1 hour appears to be due to inadequate nitroglycerin blood levels; at 24 hours it may be due to tolerance.     

Effects of isosorbide-5-mononitrate on exercise-induced hemodynamic changes in angina pectoris

Hemodynamic effects of isosorbide-5-mononitrate (ISMN) were studied in 14 patients with effort angina pectoris. Hemodynamic and echocardiographic data were obtained by angina-limited supine multistage bicycle ergometer exercise testing before and 120 minutes after single oral administration of 20 mg of ISMN. Compared with control exercise testing, the ST segment at peak exercise showed less depression after administration of ISMN (p less than 0.001). At rest, systolic and diastolic blood pressure decreased significantly after administration of ISMN (p less than 0.001 and p less than 0.01, respectively). At rest and at peak exercise, pulmonary artery wedge pressure (both p less than 0.001), left atrial volume (both p less than 0.001) and left ventricular end-diastolic volume (both p less than 0.05) decreased, whereas cardiac index, pressure-rate product and systemic vascular resistance did not change significantly after administration of ISMN. Average time to peak plasma ISMN concentration was 90 minutes and average peak plasma concentration was 460 ng/ml with an elimination half-life of 7 hours. These data suggest that the main mechanism of the antianginal action of ISMN is a reduction in left ventricular preload followed by diminution of myocardial oxygen requirements.     

Technetium-99m pyrophosphate myocardial uptake in patients with stable angina pectoris.

99m-technetium (Tc) pyrophosphate myocardial scintigrams of 55 patients with stable angina pectoris were compared with those of 13 normal subjects. The mean scintigraphic score, obtained by averaging the blinded interpretations of four readers scoring on an integral scale from 0 to 4, was significantly higher for the patients with angina than for the control subjects (1.36 compared with 0.48, P less than 0.001). Among the patients with angina, those who had a prior myocardial infarction had a higher mean scintigraphic grade than those without a previous infarction (1.73 versus 1.15, P less than 0.005), and the mean grade in both groups was higher than that of control subjects (P less than 0.001). Radionuclide uptake was predominantly diffuse in the patients with angina pectoris (70%), although in those with greater uptake accumulation tended to be localized. Three of the 68 subjects had high levels of radionuclide uptake but no clinical evidence of acute myocardial injury. This study demonstrates that excess myocardial accumulation of 99m-Tc pyrophosphate can occur in patients with stable angina pectoris.