Increased basal tone and hyperresponsiveness to acetylcholine and ergonovine in spasm related coronary arteries in patients with variant angina--basal coronary artery tone in patients with variant angina.

In patients with variant angina, previous data have been inconclusive as to whether basal coronary artery tone is elevated at the spastic and non-spastic sites. Thus, the purpose of this study was to assess the basal coronary artery tone and the responsiveness to acetylcholine (Ach) and ergonovine (Erg) in patients with variant angina. We compared the basal coronary artery tone and the constrictive responses to Ach and Erg between 31 patients (Group 1) with variant angina in whom spasm was provoked by the low doses of Ach (intracoronary 20 micrograms) or Erg(intravenous 50 micrograms) and 35 patients (Group 2) provoked by higher doses of Ach (intracoronary 100 micrograms) or Erg (intravenous cumulative dose of 350 micrograms), and 26 control subjects. Patients with variant angina in whom spasm was provoked by low doses of Ach or Erg, had a higher incidence of mixed disease, multi-vessel spasm and higher disease activity. The basal coronary artery tone at the spastic and nonspastic sites of spasm related artery was significantly more elevated in Group 1 than that in Group 2 (44 +/- 17 vs 14 +/- 11% and 26 +/- 14 vs 16 +/- 10% respectively, P < 0.05), but not in the nonspasm related artery, The magnitudes of vasoconstrictive responses to Ach and Erg at the nonspastic sites were also greater in Group 1 than those in Group 2 and the control groups (Ach; 40 +/- 20 vs 26 +/- 11, 27 +/- 12%: Erg; 37 +/- 18 vs 12 +/- 8, 13 +/- 10% respectively, P < 0.05). However, the basal coronary artery tone was not elevated at the spastic and nonspastic sites in Group 2 compared to the in control subjects. These findings suggest that the basal coronary artery tone is increased in patients with variant angina with higher disease activity at the spastic sites and nonspastic sites of the spasm-related artery, and this may be related to the occurrence of coronary artery spasm.     

Ergonovine testing in patients with exertional angina

Injection of ergonovine has been suggested as a diagnostic test in patients with suspicion of a vasospastic component in the pathophysiology of angina pectoris. However, a thorough case history has been considered by others to give the same information regarding the anginal mechanism. Therefore a bedside ergonovine test (0.075-0.675 mg i.v.) was performed in 21 consecutive patients with effort angina in order to study the relation between the outcome of the test and the case history concerning angina at rest. A coronary angiography was performed in all cases and showed significant stenoses in 17 patients and normal coronary arteries in 4. Eight patients had angina only during effort, 11 had angina both during effort and at rest and 2 patients had atypical chest pain. Ten of the 11 patients with concomitant rest angina developed chest pain at the ergonovine test and 9 coexisting ECG changes. However, these effects were about as common among the 8 patients without angina at rest: 7 developed chest pain and 4 also ECG changes. The two patients with atypical chest pain had normal coronary angiograms and in these patients ergonovine provoked the same atypical chest pain but no ECG changes. Thus, a concomitant angina at rest is a common finding among patients with severe effort angina. However, the response to ergonovine was as common in the group with only effort angina as in the group with concomitant rest angina, indicating the limited value of this test in patients with severe angina.     

Presence of hyperventilation in patients with asthma-like symptoms but negative asthma test responses: provocation with voluntary hyperventilation and mental stress

BACKGROUND: A group of patients reporting asthma-like symptoms but with negative asthma tests has been identified. OBJECTIVE: The objective of this study was to determine whether hyperventilation might explain these symptoms and whether the tests could be used as diagnostic tools. METHODS: A hyperventilation provocation test (HVPT), a mental stress test, and the Word Color Conflict Test (WCCT) were performed on 10 patients with asthma-like symptoms, 10 patients with asthma, and 10 healthy subjects. End-tidal PCO 2 (PETCO2) was recorded 10 minutes after the HVPT and during the WCCT. Blood pressure, heart rate, and respiratory rate were also studied. The Nijmegen symptom questionnaire was used in the assessment of symptoms. RESULTS: After the HVPT, the PETCO2 values recovered most slowly in the study group, the difference being significant compared with the healthy group (P <.01). During the WCCT, the study group had the lowest PETCO2 values at the 10- and 15-minute measurements, the difference again being significant compared with the healthy group (P <.05). The study group more often experienced symptoms before the test than the group with asthma (P <.05) and the healthy group (P <.001). The study group recognized significantly more symptoms previously experienced during the HVPT than the group with asthma (P <.05) and the healthy group (P <.01) and during the WCCT than the healthy group (P <.05). The study group showed a negative correlation between the PETCO2 level and the number of symptoms after the HVPT at 8 (r = -0-72; P <.05) and 10 minutes (r = -0.76; P <.05) and after the WCCT (r = -0.59; P <.05). Blood pressure, heart rate, and respiratory rate showed small differences between the groups. CONCLUSION: Patients with asthma-like symptoms may experience hyperventilation when provoked. Mental stress might be 1 trigger factor. The HVPT and WCCT can be used as diagnostic instruments.     

Vasospastic ischaemia induced by the hyperventilation test in patients with a negative response to ergometrine

We present the case histories of two patients with angina pectoris who developed coronary artery spasm in response to provocation with prolonged hyperventilation (verified by ST segment elevation in both and coronary angiography in one) despite a negative ECG response to intravenous injection of 0.4 mg ergometrine. This new observation, which is in conflict with recent publications stating that ergot provocation is more sensitive than hyperventilation, suggests that in some patients diagnostic provocation with hyperventilation may be an alternative to the widely used ergot provocation.     

Effect of intracoronary serotonin on coronary vessels in patients with stable angina and patients with variant angina

BACKGROUND. Serotonin, a major product of platelet activation, has potent vasoactive effects in animal models, but its role in human coronary artery disease remains largely speculative. METHODS. Using quantitative coronary angiography, we compared the effects of the intracoronary infusion of graded concentrations of serotonin (10(-7) to 10(-4) mol per liter) on coronary vessels in two groups of patients with different clinical presentations of coronary disease (nine with stable angina and five with variant angina), with the effects in a control group of eight subjects with normal vessels on angiography. RESULTS. Normal coronary vessels had a biphasic response to intracoronary serotonin: dilation at concentrations up to 10(-5) mol per liter, but constriction at 10(-4) mol per liter. Vessels in patients with stable angina constricted at all concentrations, with mean (+/- SEM) maximal decreases in diameter of 23.9 +/- 3.6, 33.1 +/- 3.9, and 41.7 +/- 3.1 percent from base line in proximal, middle, and distal segments at a serotonin concentration of 10(-4) mol per liter. Smooth segments constricted more than irregular segments (42.0 +/- 4.6 vs. 21.1 +/- 1.6 percent). Four patients with stable angina had a marked reduction in collateral filling. All the patients with stable angina had angina during the intracoronary infusion of serotonin, and electrocardiographic changes were noted in six. All the patients with variant angina had angina, electrocardiographic changes, and localized occlusive epicardial coronary-artery spasm at concentrations of 10(-6) (n = 2) or 10(-5) (n = 3) mol per liter. CONCLUSIONS. Patients with stable coronary disease do not have the normal vasodilator response to intracoronary serotonin, but rather have progressive constriction, which is particularly intense in small distal and collateral vessels. Patients with variant angina have occlusive coronary-artery spasm at a dose that dilates normal vessels and causes only slight constriction in vessels from patients with stable angina. These findings suggest that serotonin, released after the intracoronary activation of platelets, may contribute to or cause myocardial ischemia in patients with coronary artery disease.     

Increases in lipids and immune cells in response to exercise and mental stress in patients with suspected coronary artery disease: effects of adjustment for shifts in plasma volume

This study examined the role of shifts in plasma volume on lipid and immune reactions to stress. Lipid, immune, rheological, and cardiovascular reactions to exercise and mental stress in 51 patients with suspected coronary artery disease were determined. Blood pressure and heart rate were measured during and blood samples taken at the end of each rest and task. Lipids (total cholesterol, triglycerides, HDL, LDL) and immune cells (lymphocytes, monocytes, granulocytes) increased with exercise, whereas cholesterol, LDL, and lymphocytes increased with mental stress. Plasma volume decreased by 1 and 5% following mental and exercise stress, respectively. The task-induced increases in lipids were no longer statistically significant following adjustment for changes in plasma volume, whereas the increases in immune cell numbers survived such correction. This study provides evidence that, in coronary artery disease patients, exercise and mental stress-induced increases in lipids but not immune cells can be largely accounted for by shifts in plasma volume.     

Exercise induced asthma: response to disodium cromoglycate in skin-test positive and skin-test negative subjects

Thirty-nine asthmatic subjects, aged 5-50 and each with a history of exercise-induced asthma, were classified according to their skin response to prick tests using nineteen common antigens. Ten had negative skin tests, four responded only to D. farinae and twenty-five had multiple positive responses. Each patient then carried out three exercise tests on a treadmill, each test on a separate day. A control test was followed, in random order, by an exercise test after administration of disodium cromoglycate or of a placebo. In all groups, the mean fall in peak expiratory flow rate was less after disodium cromoglycate than after placebo, but the difference was significant only for the skin-test positive groups. Similarly, positive skin-test groups had a higher incidence of drug responders than did the negative skin-test group. These observations are discussed.     

Changes in plasma volume associated with mental stress ischemia in patients with coronary artery disease.

Psychological stress has been shown to trigger angina and myocardial ischemia in patients with coronary artery disease. However, the mechanisms by which stress may trigger cardiac events has yet to be fully elucidated. Twenty five patients underwent radionuclide ventriculography during a multiple stress challenge. Plasma volume was assessed during rest and at the end of the stress task. Flow-mediated dilatation was also measured. Controlling for endothelial function and medications, patients with ischemia had greater reductions in plasma volume than non-ischemic patients. Reduced plasma volume may be one mechanism by which mental stress may increase the risk for acute coronary events.     

The influence of aerobic fitness status on ventilatory efficiency in patients with coronary artery disease

OBJECTIVE:

To test the hypotheses that 1) coronary artery disease patients with lower aerobic fitness exhibit a lower ventilatory efficiency and 2) coronary artery disease patients with lower initial aerobic fitness exhibit greater improvements in ventilatory efficiency with aerobic exercise training.

METHOD:

A total of 123 patients (61.0±0.7 years) with coronary artery disease were divided according to aerobic fitness status into 3 groups: group 1 (n = 34, peak VO₂<17.5 ml/kg/min), group 2 (n = 67, peak VO₂>17.5 and <24.5 ml/kg/min) and group 3 (n = 22, peak VO₂>24.5 ml/kg/min). All patients performed a cardiorespiratory exercise test on a treadmill. Ventilatory efficiency was determined by the lowest VE/VCO₂ ratio observed. The exercise training program comprised moderate-intensity aerobic exercise performed 3 times per week for 3 months. Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT02106533","term_id":"NCT02106533"}}NCT02106533

RESULTS:

Before intervention, group 1 exhibited both lower peak VO₂ and lower ventilatory efficiency compared with the other 2 groups (p<0.05). After the exercise training program, group 1 exhibited greater improvements in aerobic fitness and ventilatory efficiency compared with the 2 other groups (group 1: ▵ = -2.5±0.5 units; group 2: ▵ = -0.8±0.3 units; and group 3: ▵ = -1.4±0.6 units, respectively; p<0.05).

CONCLUSIONS:

Coronary artery disease patients with lower aerobic fitness status exhibited lower ventilatory efficiency during a graded exercise test. In addition, after 3 months of aerobic exercise training, only the patients with initially lower levels of aerobic fitness exhibited greater improvements in ventilatory efficiency.     

Exercise training enhances relaxation of the isolated guinea-pig saphenous artery in response to acetylcholine

The effects of exercise training were investigated on the vascular responses in the isolated guinea-pig saphenous artery. Exercising animals swam 5 days week-1 for 6 weeks (60 min day-1 for weeks 1 and 2; 75 min day-1 for weeks 3 and 4; 90 min day-1 for weeks 5 and 6), while control animals were placed into shallow water for the same duration. Trained animals had significantly higher ventricular:body weight ratios, increased citrate synthase activity in the latissimus dorsi, and enhanced Na+ pump concentrations in the latissimus dorsi and gastrocnemius muscles (P < 0.05). In vitro isometric techniques were used to measure constriction and relaxation responses of saphenous artery rings from trained and control animals. There were no significant differences in the constriction responses to KCl (50 mm) and phenylephrine (0.3-100 microM) in arterial rings from control versus trained animals. Relaxation responses to acetylcholine (10 microM; ACh-relaxation), following preconstriction with phenylephrine (10 microM), were significantly enhanced in rings from trained animals (P < 0.05). Acetylcholine relaxed the vessels to 47 +/- 6% (control) and 18 +/- 3% (trained) of the preconstriction responses to phenylephrine. The nitric oxide synthase inhibitor N G-nitro-L-arginine (L-NA; 50 microM) significantly attenuated the ACh-relaxation in control and trained animals (P < 0.05). The effect of L-NA on the ACh-relaxation was significantly larger in trained (change in ACh-relaxation with L-NA = 29 +/- 9%) than control (14 +/- 3%) animals (P < 0.05). In conclusion, exercise training enhanced the ACh-relaxation of the isolated guinea-pig saphenous artery. Inhibition of nitric oxide synthase attenuated the ACh-relaxation of rings from control and trained animals, but this effect was significantly larger in the vessels from trained animals. These results are consistent with the idea that nitric oxide could contribute to the enhanced ACh-relaxation of the saphenous artery with exercise training.     

Increased plasma levels of thioredoxin in patients with coronary spastic angina

To determine whether plasma levels of thioredoxin are associated with coronary spasm, we measured the plasma levels of thioredoxin in 170 patients who had <25% organic stenosis in coronary arteriography. According to the results of cardiac catheterization, we divided the patients into two groups: a coronary spastic angina group (n=84) and a chest pain syndrome group (n=86). The plasma levels of thioredoxin were significantly higher in the coronary spastic angina group than in the chest pain syndrome group (40.7 +/- 4.1 versus 18.2 +/- 1.1 ng/ml, p<0.0001). Furthermore, the increased plasma levels of thioredoxin were associated with high disease activity indicated by the frequency of angina attacks (p=0.0004). In multiple logistic regression analysis, the higher levels of thioredoxin [relative risk 14.8, 95% confidence interval (5.13-42.9), p<0.0001] and current smoking [relative risk 3.39, 95% confidence interval (1.31-8.75), p=0.012] were significant and independent variables associated with coronary spasm. We demonstrated that the plasma levels of thioredoxin were increased in the coronary spastic angina group, and increased levels of thioredoxin were associated with high disease activity. The plasma levels of thioredoxin and current smoking were risk factors for coronary spastic angina, and they were independent from other traditional risk factors.     

大剂量血脂康在经皮冠状动脉介入术中的炎症抑制作用

目的： 研究不稳定型心绞痛(UA)患者在经皮冠状动脉介入(PCI)治疗前应用大剂量血脂康对炎症的抑制作用。 方法： 对196例临床确诊为高危UA（心绞痛Braunwald 分级为Ⅲ和ⅡB级,CRP＞3 mg/L）的患者按随机原则分别入选A组和B组,在相似常规治疗的基础上分别口服1.2 g/d和2.4 g/d血脂康治疗72 h。随后对所有病人进行冠状动脉造影和PCI治疗。测定在入院时、药物治疗3 d后（PCI术前）和PCI术后48 h的血浆CRP的水平，并随访半年内的冠脉事件和左室射血分数。 结果： 入院时2组血浆CRP水平无明显差别（P＞0.05）；治疗3 d后，两组血浆CRP水平明显低于入院时［A组：（5.44±1.57）mg/L vs （4.04±1.54） mg/L；B组： （5.42±1.36） mg/L vs （3.60±1.14） mg/L,P＜0.05］；PCI术后48 h，两组血浆CRP水平显著高于术前［A组升至 （9.22±5.03） mg/L；B组升至（4.97±1.75） mg/L，P＜0.05］。PCI术前及术后48 h，B组的血浆CRP水平明显低于同期A组(P＜0.05)。术后半年主要冠脉事件B组明显少于A组［21/104 (20.2%) vs 9/92 (9.8%)，P＜0.05］，左室射血分数B组明显高于A组(55.41％±10.93% vs 59.30％±9.99%,P＜0.05)。 结论： PCI术前大剂量血脂康治疗对PCI术引起的炎症具有抑制作用，抑制炎症可能是PCI术后冠脉事件减少和左室射血分数增加的重要因素。     

Perivascular nerve lesion of the coronary artery involved in spasm in a patient with variant angina

An autopsy case of a 52-year-old man with typical variant angina is reported. He had recurrent attacks of chest pain at rest, particularly from midnight to early morning, associated with ST segment elevation in the electrocardiogram. At autopsy, degenerative changes and fibrosis were confirmed light microscopically in the perivascular nerves of the coronary artery involved in spasm. This finding indicates an intimate relationship between coronary spasm and the autonomic nervous system.     

Carotid artery stenting in patients with symptomatic coronary artery disease

Carotid artery stenting has been accepted as a potential alternative to carotid endarterectomy in patients with significant carotid artery stenosis. The objective of this study was to evaluate the feasibility, safety and long-term outcome of percutaneous stenting of carotid artery stenosis in patients with coexisting symptomatic coronary disease. Between May 1996 and May 1999, we performed carotid artery stenting at 48 lesions in 36 patients with carotid stenosis of 60% and symptomatic coronary artery stenosis. Twenty-one patients (58%) had neurologic symptoms. Carotid stenting was performed in 43 internal, 2 external and 3 common carotid lesions. We used Wallstent in 46 lesions, Palmaz stent in 2 lesions and Microstent II in 1 lesion. Staged or combined coronary intervention was performed in 18 patients (50%) and staged coronary artery bypass surgery was performed in 6 patients (17%). In the other 12 patients (33%), medical treatments were performed. Carotid stenting was successful in all lesions. Simultaneous bilateral carotid stenting was performed in 11 patients (31%). One major and 1 minor stroke developed during the procedure. There were no deaths during the procedures and within 30 days post-procedure. During the follow-up of 14 +/- 7 (3 to 40) months, there were no deaths or neurological events. On follow-up (6 +/- 1 months) angiography and/or duplex sonography of 44 eligible lesions in 32 patients, there were 2 cases of asymptomatic restenosis (4.5%) which developed in Palmaz stents implanted at the external carotid artery and the common carotid artery, respectively. In conclusion, carotid artery stenting in patients with coexistent carotid and coronary artery disease is feasible, safe and shows favorable follow-up outcomes.     

Impaired flow-mediated vasodilation of epicardial coronary artery in vasospastic angina.

To evaluate whether the flow-mediated vasodilation and coronary flow reserve are impaired or not in patients with vasospastic angina (VA), we measured the changes of epicardial coronary artery diameter and flow reserve in spasm related-left anterior descending coronary artery (LAD). The flow mediated-response of epicardial coronary arteries in 15 VA were compared with 15 controls. Using quantitative coronary angiography, we measured the diameter of proximal (pLAD) and middle segment (mid-LAD) of LAD under baseline conditions, during increased blood flow after distal adenosine injection and after proximal administration of nitroglycerin. An increased fraction of average peak velocity after injection of adenosine was similar in both groups [control 340 (mean)+/-24 (SEM)%; VA 330+/-19%]. Flow-mediated vasodilation was preserved in all controls (pLAD 13.1+/-1.4%; mid-LAD 15.8+/-2.5%) but it was significantly impaired in patients with VA (pLAD -1.0+/-1.8%; mid-LAD 0.1+/-3.5%). The vasodilator response to nitroglycerin was comparable in controls (pLAD 25.8+/-2.8%; mid-LAD 27.2+/-2.8%) and VA (pLAD 26.2+/-5.2%; mid-LAD 26.7+/-3.5%). Coronary flow reserve is preserved in patients with VA. However, the flow-mediated response of spasm related-epicardial coronary artery is impaired. This may play an important role in the pathogenesis of coronary artery spasm.