Systemic neurohumoral activation and vasoconstriction during pacing-induced acute myocardial ischemia in patients with stable angina pectoris

To identify the effect of myocardial ischemia on systemic neurohormones and vascular resistance, 32 untreated, normotensive patients with coronary artery disease underwent incremental atrial pacing until angina. Arterial and coronary venous lactate and arterial values of catecholamines and angiotensin II were determined at control, at maximal pacing rates, and at 1, 2, 5 and 30 minutes after pacing. Based on pacing-induced ST-segment depression (greater than or equal to 0.1 mV) or myocardial lactate production, or both, patients were selected as ischemic (n = 25) or nonischemic (n = 7). Baseline clinical and hemodynamic data were comparable. During pacing, chest pain was similar (20 ischemic vs 7 nonischemic patients). Also, hemodynamic measurements were comparable, except for contractility, which did not improve, and left ventricular end-diastolic pressure, which significantly increased in ischemic patients. Moreover, during ischemia arterial pressures increased significantly (13%) and systemic resistance increased from 1,470 +/- 60 (control) to 1,632 +/- 76 dynes.s.cm-5 5 minutes after pacing (p less than 0.05) in ischemic but not in nonischemic patients. Pacing did not affect neurohormones in nonischemic patients. In contrast, norepinephrine in ischemic patients increased significantly from 1.7 +/- 0.2 (control) to 2.6 +/- 0.3 (maximal pacing) and to 3.0 +/- 0.4 nmol/liter (1 minute after pacing), whereas angiotensin II levels increased from 6.2 +/- 1.4 (control) to 9.3 +/- 2.1 pmol/liter (1 minute after pacing, p less than 0.05). Epinephrine only increased during maximal rates (0.9 +/- 0.1 vs 0.6 +/- 0.1 nmol/liter at control, p less than 0.05). Thus, myocardial ischemia activates circulating catecholamines and angiotensin II, accompanied by systemic vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Characteristics of symptomatic and asymptomatic myocardial ischemia during ambulatory electrocardiographic monitoring in patients with angina pectoris

The purpose of the present study was to clarify the characteristics of myocardial ischemic attacks in patients with exertional angina (EA, 56 cases), exertional and rest angina (ERA, 28 cases), rest angina (RA, 4 cases), and variant angina (VA, 39 cases). The Holter electrocardiographic findings were compared among the four types of angina pectoris. The frequency of symptomatic ischemic attacks in descending order was 46.0% in EA, 29.0% in ERA, 28.1% in RA, and 21.6% in VA, while the frequency of asymptomatic ischemic attacks was in the reverse order. The maximal heart rates during symptomatic ischemic attacks were in descending order, EA, ERA, RA, and VA. The maximal heart rate during ischemic attacks was significantly lower in patients with spontaneous angina than in those with exercise-induced ischemia for all types of angina (p less than 0.05, respectively). Further, the difference in maximal heart rate during ischemic attacks between the ambulatory electrocardiogram and exercise test was greater in patients with RA and VA than in those with EA. Therefore, this suggests that increased coronary vascular tone is a cause of spontaneous ischemic attacks in each type of angina pectoris.     

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.     

Elevated pain threshold in patients with effort-induced angina pectoris and asymptomatic myocardial ischemia during exercise test

The purpose of the present study was to analyze the prevalence of asymptomatic (silent) myocardial ischemia during exercise testing among patients with effort-induced angina pectoris, and further, to compare the pain threshold of patients with symptomatic and asymptomatic myocardial ischemia. A group of 26 patients comprised the study. In half of the patients myocardial ischemia during the exercise testing was silent and in one half it was symptomatic. Asymptomatic myocardial ischemia was defined as an asymptomatic ST-segment depression greater than or equal to 0.1 mV, lasting longer than 60 s during an exercise test. In patients with asymptomatic ischemia the pain thresholds both on toe and finger were significantly higher than in patients with symptomatic ischemia: mean values were 10.1 versus 4.9 mA on the toes, p less than 0.025, and 8.4 versus 2.5 mA on the fingers, p less than 0.01. We conclude that asymptomatic myocardial ischemia during exercise test is seen often in patients with angina pectoris and that this may be due to an increased pain threshold.     

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。     

Clinical significance and management of silent myocardial ischemia in patients with angina pectoris and myocardial infarction

The present study was canued out to clarify the relationship between silent myocardial ischemia in patients with angina pectoris and onset of myocardial infarction, and the former's prognostic significance. The peak incidences of onset of myocardial infarction in patients were at 2 a.m., 9 a.m., 2 p.m., 8 p.m., and 9 p.m., and the peak onsets of transient silent myocardial ischemia in angina pectoris patients were at 9 a.m., 2 p.m., 8 p.m., and 9 p.m. Thus the most likely onset times were almost the same with both events. Of 169 patients with coronary artery disease admitted for treatment, 128 patients had no anginal attacks during follow-up and the remaining 41 had persistent angina despite adequate medical treatment. Holter monitoring electrocardiography was performed twice with the non-angina patients, during admission. Of these 128 patients, 54 showed no silent myocardial ischemia on either of the electrocardiographic recordings, 34 showed silent ischemia with the first Holter monitoring but not with the second one, and the remaining 41 showed silent myocardial ischemia on both tests. The subsequent incidences of "cardiac events" were 9.4%, 14.7%, and 36.6%, respectively for these three groups. Therefore, it is concluded that the presence of silent myocardial ischemia is closely related to onset of myocardial infarction and is an important prognostic factor in patients with coronary artery disease.     

Incidence, characteristics and coronariographic significance of myocardial ischemia during daily life in patients with angina pectoris

OBJECTIVES: To evaluate the incidence, characteristics and angiographic significance of myocardial ischemia detected on Holter monitoring in a group of patients with stable angina pectoris. SETTING: Department of Cardiology of a Central Terciary Hospital. METHODS: In 24 patients (pts) with stable angina pectoris and proven coronary artery disease (11 pts with left main or three vessel disease; 13 pts with one or two vessel disease), a 24 hour Holter monitoring was performed. Two groups of ischemic episodes were considered: Group I with 65 ischemic episodes detected in pts with left main or three vessel disease and group II constituted by 17 ischemic episodes detected in pts with one or two vessel disease. RESULTS: The incidence of myocardial ischemia was 91% in pts with left main or three vessel disease and 46% in pts with one or two vessel disease. Statistically significant differences were seen between group I and II concerning the mean heart rate variation from two minutes before onset of ST-segment depression to its onset (3.5 bpm vs 7.4 bpm; p less than 0.05) and from the onset of ST-segment depression to its maximal depression (6.5 bpm vs 15 bpm; p less than 0.000001). CONCLUSIONS: The presence of myocardial ischemia and some of its characteristics on Holter monitoring seem to have a relation with the severity of coronary artery disease in patients with stable angina pectoris.     

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.     

Prognostic implications of exercise induced silent myocardial ischemia in patients with angina pectoris

To clarify the prognostic implications of exercise induced silent myocardial ischemia (SMI) in patients with angina pectoris, the clinical characteristics and long-term prognosis after coronary angiography in 379 patients without prior myocardial infarction were investigated. According to the results of treadmill testing and/or Tl-201 exercise imaging after medical treatment, 50 patients with negative for ischemia were classified as control group, 110 patients with exercise induced SMI were classified as the SMI group, and 187 patients with painful ischemia formed the PI group. Thirty-two patients were excluded because of inconclusive exercise results. Single vessel disease and vasospastic angina were more frequent in the control group than in the SMI and PI groups. But there were no differences in baseline characteristics and extent of coronary lesions between the latter two groups. Heart rate, systolic blood pressure and rate-pressure product at end point in treadmill testing were higher in the control and SMI groups than in the PI group. The mean follow-up period was 4.8 years, and follow-up was completed in every case. Cardiac events, including cardiac death, nonfatal myocardial infarction and readmission from severe angina, occurred in 25 patients of the SMI group, 43 of the PI group and 7 of the control group. Cumulative cardiac event curves did not show any statistically significant difference between the SMI and PI groups. We conclude the presence or absence of angina during exercise test is no longer the principal prognostic index for determining a patient's risk of cardiac events.     

卡托普利对心绞痛患者流变学和心肌缺血的影响

目的 :观察卡托普利对心绞痛患者血流变各项指标和心肌缺血发作的影响。方法 :5 1例心绞痛患者随机分为卡托普利组和对照组 ,观察患者血流变各项指标和心绞痛患者心肌缺血发作的情况。结果 :卡托普利能显著降低心绞痛患者高、低切变率时的全血粘度 ,全血高、低切还原粘度。卡托普利能明显改善心绞痛患者红细胞的变形性、心绞痛程度显著降低、心绞痛持续时间显著缩短。卡托普利对心绞痛患者血浆粘度、红细胞压积、纤维蛋白原、血压、血糖均无明显影响。结论 :卡托普利能显著降低血液粘度 ,改善心绞痛患者红细胞的变形性、显著降低心绞痛程度、心绞痛持续时间显著缩短 ,有利于改善微循环灌注 ,改善心脏供血、供氧 ,有利于预防动脉血栓形成和降低急性心肌梗死的发病率     

Association of endothelin-1 with transient myocardial ischemia in patients with unstable angina pectoris

In this study we assessed whether serum endothelin-1 levels were associated with indexes of disease severity in unstable angina, including troponin I, C-reactive protein, and transient myocardial ischemia. Endothelin-1 levels were higher in patients who had transient myocardial ischemia and in those who had 3-vessel disease on angiography but were not significantly correlated with levels of C-reactive protein and troponin I.     

Prognosis in stable angina pectoris and silent myocardial ischemia

The results of current investigation suggest that a former clinical standby, namely, the presence or absence of angina, is no longer the principal prognostic factor for determining a patient's risk of cardiac events, including myocardial infarction. In a retrospective analysis, patients with chronic stable angina were compared on the basis of presence or absence of angina during ischemia detected by thallium imaging. Patients were similar in terms of risk factors, clinical characteristics and catheterization data. At 30 months of follow-up, the myocardial infarction rate was 22% in the silent group compared with 4% in the group with angina. Transient asymptomatic ischemia has prognostic value independent of other variables such as exercise stress testing or cardiac catheterization data. Future prognostic studies should be careful to include patient populations with similar characteristics; they also will need to provide protracted follow-up and utilize sensitive and reproducible diagnostic techniques.     

The relation between myocardial oxygen consumption and ischemia during exertion in patients with angina pectoris: effect of propranolol

Patients with coronary artery disease exhibit a reduced coronary vasodilator reserve in response to exercise testing. Drugs which block coronary beta adrenergic receptors could exacerbate this abnormality leaving the vasoconstrictor alpha tone unopposed and/or counteracting the beta 2-mediated vasodilation elicited by the increase in myocardial oxygen demand. To test this hypothesis we administered propranolol 40 mg qid and placebo, using a cross over randomized single blind protocol, to 14 patients each with effort angina and critical coronary stenosis (greater than or equal to 75%). We performed computer-assisted multistage bicycle ergometer testings (25 W increments at 2 min intervals) after 2 weeks open label placebo (control) and at 2 week intervals following daily administration of propranolol and placebo. Compared to placebo, propranolol reduced significantly (p less than 0.001) peak heart rate (x +/- SD: 114 +/- 6 vs 150 +/- 11 beats/min) and rate pressure product (20.1 +/- 2.1 vs 28.0 +/- 3.9 X 10(-3)) and increased exercise duration (462 +/- 91 vs 355 +/- 85 sec). Conversely 0.1 mV ST segment depression was observed at lower heart rate (106 +/- 9 vs 127 +/- 8 beats/min, p less than 0.001) and rate pressure product (16.9 +/- 3.6 vs 22.4 +/- 2.4 X 10(-3), p less than 0.001). No significant differences were found between placebo and control. Moreover, we assessed the regression lines of the relationship between ST segment depression (ST) and heart rate (HR) during exercise. These have been shown to be shifted to the right after surgical revascularization and are an indirect measure of coronary reserve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early detection of myocardial ischemia by myocardial free fatty acid extraction in patients with exercise-induced angina pectoris

This study investigated whether the measurement of plasma free fatty acids (FFAs) could assist in the early detection of exercise-induced myocardial ischemia. Fifteen subjects with effort angina pectoris underwent angina-limited supine bicycle ergometer exercise testing. Myocardial FFA extraction decreased significantly from 22.8 +/- 3.1% at rest to 7.7 +/- 1.5% at peak exercise (p less than 0.05). Myocardial lactate extraction showed no significant change between rest and peak exercise. After control exercise testing, 8 subjects were given a single oral dose of nilvadipine (6 mg) and then again underwent exercise testing for the same duration. Nilvadipine lessened or abolished chest pain and there was less depression of the ST segment at peak exercise. Furthermore, myocardial FFA extraction showed no significant change between rest and peak exercise after nilvadipine administration. These results suggest that myocardial FFA extraction can be used to assess the presence of exercise-induced myocardial ischemia at an earlier stage than myocardial lactate extraction.     

Women react with more myocardial ischemia and angina pectoris during elective percutaneous transluminal coronary angioplasty

BACKGROUND: Women have been considered to be at higher risk of complications relating to percutaneous transluminal coronary angioplasty (PTCA) than are men. One reason for this sex-related difference could be the ischemic response of myocardium during the procedure. OBJECTIVE: To investigate whether there are sex-related differences in ischemic response of myocardium during elective PTCA. METHODS: Consecutive patients (n = 192, of whom 48 were women), were subjected to vectorcardiography during the PTCA procedure. Vectorcardiographic variables, magnitude of ST-segment vector (ST-VM), and magnitude of ST-segment vector change (STC-VM) were studied. RESULTS: Women were older (63 +/- 10 versus 56 +/- 10 years, P< 0.001) than men in our study and more often had diabetes mellitus and hypertension. Women less often had stents implanted (24 versus 50%, P < 0.01) and they were subjected to fewer balloon inflations (P < 0.001), with a total inflation time shorter than that for men (P< 0.001). Maximum STC-VM was 25% greater for women (P < 0.05). Women reported greater maximum pain (P < 0.05) and nitroglycerine was more frequently used for them during PTCA (P < 0.05). Occurrence of episodes of residual ischemic STC-VM (the difference between total number of episodes and number of balloon inflations) was more common for women (3 +/- 5 versus 1 +/- 3, P< 0.01). Duration of residual ischemic STC-VM episodes (the difference between total duration of episodes and duration of balloon inflations) was longer for women than it was for men (242 +/- 275 versus 148 +/- 233 s, P < 0.05). In a stepwise multivariate analysis and for a matched case-control group, episodes of residual STC-VM and duration of residual STC-VM episodes still indicated that there was an independent sex-related difference (P < 0.01 and P < 0.01, respectively). CONCLUSIONS: Women more commonly develop vectorcardiographic signs of severe myocardial ischemia, more frequently experience episodes of ischemia and report more severe angina pectoris during elective PTCA than do men.     

The QRS complex during transient myocardial ischemia: studies in patients with variant angina pectoris and in a canine preparation

We made continuous electrocardiographic recordings on magnetic tape during 15 episodes of ischemia in five patients with variant angina to determine the characteristics of the QRS changes. Orthogonal leads were used and the electrocardiograms were analyzed visually and by digital computer. Changes were quantified by subtracting baseline electrocardiograms from those obtained during ischemia. Large changes in the QRS occurred during ischemia but the waveform quickly returned to baseline when the episode subsided. In all patients there was prolongation of the QRS duration and an increase in QRS voltage during the terminal 40 msec of the waveform in the lead(s) showing the most marked ST displacement. The increase in the terminal QRS could be represented by a vector directed toward the ischemic zone. In a given patient the amplitude of ST displacement varied between episodes, presumably because of variation in the intensity of ischemia, but the QRS changes were directionally similar in each episode. In two patients there was also a smaller change involving the initial 40 msec of the QRS that could be represented by a vector directed away from the ischemic zone. To determine the possible mechanism for the electrocardiographic changes, ischemic episodes of 120 to 150 sec were produced in seven dogs and electrocardiographic recording and analysis techniques similar to those used in patients were employed. Myocardial conduction velocity was measured in three directions in the ischemic zone and was correlated with simultaneous electrocardiographic recordings from the body surface. The electrocardiographic changes in the dog preparation were virtually identical to those in the patients and strongly correlated with a fall in myocardial conduction velocity. We conclude that the QRS changes during variant angina result from the altered excitation pattern produced by conduction delay in the ischemic zone. The probable cause for the increase in terminal QRS voltage is delayed (and uncancelled) activation of the ischemic zone.     

Comparison of C-reactive protein and terminal complement complex in patients with unstable angina pectoris versus stable angina pectoris

Elevated C-reactive protein (CRP) can identify patients with coronary artery disease who are prone to future acute events. We investigated whether elevated CRP is related to the activation of the terminal complement cascade in 66 patients with unstable angina pectoris (UAP), in 45 patients with stable angina pectoris, and in 42 controls. CRP, additional acute phase reactants, the terminal complement complex (sC5b-9), leukocytes, and troponin T were measured. In 47 patients with UAP the CRP values were regarded as elevated (>0.3 mg/dl). In patients with UAP and elevated CRP, the plasma levels of sC5b-9 were markedly higher than in patients with UAP and lower CRP (245 +/- 14 vs 188 +/- 19 ng/ml, p <0.02) and in patients with stable angina pectoris with slightly (0.4 +/- 0.1 mg/dl) increased CRP (sC5b-9 173 +/- 21 vs 130 +/- 7 ng/ml [controls; p <0.05]). A further acute phase reaction was present only in patients with UAP and elevated CRP already on admission (p <0.01). sC5b-9 was not related to troponin release. Thus, elevated CRP levels are associated with activation of the plaque destabilizating terminal complement system in patients with UAP during the acute phase reaction. This may explain the prognostic value of CRP in acute coronary syndromes (ACS).     

Anti-ischemic effects of amlodipine in patients with stable angina pectoris and myocardial ischemia during daily life. Amlodipine Study Group

Ambulatory electrocardiographic monitoring was used to assess the anti-ischemic effects of amlodipine in a subset of 56 patients enrolled in a 14-week withdrawal study; amlodipine therapy resulted in a marked decrease in the overall mean number of ischemic events and the average number of transient ischemic episodes (p <0.005). Amlodipine substantially reduced the number of ischemic events among all patients during the single-blind phase, with further significant reductions recorded among patients who remained on amlodipine during double-blind therapy, but the number of ischemic events increased almost to baseline levels in patients switched to placebo during double-blind therapy (p = 0.01 by analysis of variance).