Occurrence Of Coronary Artery Spasm Research Articles

Reactive oxygen species in cardiovascular health and disease: special references to nitric oxide, hydrogen peroxide, and Rho-kinase.

The interaction between endothelial cells and vascular smooth muscle cells (VSMC) plays an important role in regulating cardiovascular homeostasis. Endothelial cells synthesize and release endothelium-derived relaxing factors (EDRFs), including vasodilator prostaglandins, nitric oxide (NO), and endothelium-dependent hyperpolarization (EDH) factors. Importantly, the contribution of EDRFs to endothelium-dependent vasodilatation markedly varies in a vessel size-dependent manner; NO mainly mediates vasodilatation of relatively large vessels, while EDH factors in small resistance vessels. We have previously identified that endothelium-derived hydrogen peroxide (H2O2) is an EDH factor especially in microcirculation. Several lines of evidence indicate the importance of the physiological balance between NO and H2O2/EDH factor. Rho-kinase was identified as the effectors of the small GTP-binding protein, RhoA. Both endothelial NO production and NO-mediated signaling in VSMC are targets and effectors of the RhoA/Rho-kinase pathway. In endothelial cells, the RhoA/Rho-kinase pathway negatively regulates NO production. On the contrary, the pathway enhances VSMC contraction with resultant occurrence of coronary artery spasm and promotes the development of oxidative stress and vascular remodeling. In this review, I will briefly summarize the current knowledge on the regulatory roles of endothelium-derived relaxing factors, with special references to NO and H2O2/EDH factor, in relation to Rho-kinase, in cardiovascular health and disease.

The Biochemical Markers Associated with the Occurrence of Coronary Spasm.

Coronary artery spasm (CAS) is one of the mechanisms of angina pectoris. Unlike the diagnosis of acute myocardial infarction which is based on the elevation of cardiac markers, the diagnosis of CAS is difficult and sometimes requires sophisticated and risky provocative test which is not widely accepted in China. There is no well-established biomarker for the diagnosis or prediction of CAS. However, there are some biomarkers proven to be associated with the occurrence of CAS. For example, inflammatory factors including C-reactive protein and cytokines, lipoprotein (a), and cystatin-C might be precipitating factor for CAS. Rho-kinase as a mediator involved in multiple mechanisms of CAS, serotonin, and endothelin-1 as powerful vasoconstrictors leading to vasospasm were all observed being elevated in patients with CAS. Thioredoxin and nitrotyrosine reflected the oxidative status and could be observed to be elevated after the occurrence of CAS. In some cases doubted to be CAS without the evidence of provocative test, the blood test for the biomarkers mentioned above could be useful for the diagnosis of CAS.

Vitamin E deficiency in variant angina.

Oxidative modification of LDL has been suggested to increase coronary vasoreactivity to agonists. A deficiency of vitamin E, a major antioxidant, may be related to the occurrence of coronary artery spasm. Vitamin E levels were determined with the use of high-performance liquid chromatography in normolipidemic subjects, including 29 patients with active variant angina (group 1), 13 patients with inactive stage of variant angina without anginal attacks during the past 6 months (group 2), 32 patients with a significant (>75%) organic coronary stenosis and stable effort angina (group 3), and 30 patients without coronary artery disease (group 4). Total lipid levels in blood were calculated as total cholesterol plus triglyceride levels. The plasma alpha-tocopherol levels as well as alpha-tocopherol/lipids were significantly lower in group 1 than in groups 2 through 4. Also, the plasma gamma-tocopherol levels were significantly lower in group 1 than in groups 2 through 4. The vitamin E levels were not significantly different between group 1 patients with and those without a significant organic stenosis. In group 1, both alpha- and gamma-tocopherol levels were significantly elevated after a > or = 6-month angina-free period. The alpha-tocopherol levels in the LDL fraction were significantly lower in group 1 than in group 4. Plasma alpha-tocopherol levels were significantly correlated with those in the LDL fractions. In 6 patients of group 1 still having anginal attacks while receiving calcium channel blockers, the addition of vitamin E acetate (300 mg/d) significantly elevated plasma alpha-tocopherol levels and inhibited the occurrence of angina. Plasma vitamin E levels were significantly lower in patients with active variant angina than in subjects without coronary spasm, suggesting an association between vitamin E deficiency and coronary artery spasm.

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.

Comparison of epicardial coronary artery tone and reactivity in Prinzmetal's variant angina and chronic stable angina pectoris

It has been suggested that a generalized coronary vasomotion disorder is present in variant angina and that evaluation of baseline coronary artery tone may be useful for predicting the occurrence of coronary artery spasm. The vasomotor response of angiographically normal proximal and distal coronary artery segments was studied in 9 patients with atypical chest pain and normal coronary arteriograms (control group), 13 patients with active variant angina and 41 patients with chronic stable angina. Ergonovine (intravenous, 100 to 300 μg, or intracoronary, 8 to 20 μg, was administered to all 22 patients in the control and variant angina groups and to 11 of the 41 patients with chronic stable angina. All patients also received intracoronary isosorbide dinitrate (1 to 2 mg).Computerized coronary artery diameter measurement of angiographically normal segments was carried out before and after ergonovine and nitrate administration. Mean baseline intraluminal diameter of proximal and distal coronary segments was not significantly different in control patients and those with variant angina (nonspastic segments only) or coronary artery disease (proximal 2.89 ± 0.15, 2.83 ± 0.14 and 2.82 ± 0.09 mm; distal 1.60 ± 0.08, 1.63 ± 0.07 and 1.62 ± 0.06 mm, respectively). After ergonovine, proximal segments constricted by 10 ± 2%, 15 ± 3% and 11 ± 4% and distal segments by 11 ± 3%, 11 ± 2% and 14 ± 3% in control, variant angina and coronary artery disease groups, respectively (p = NS). After isosorbide dinitrate, proximal coronary segments dilated by 13 ± 2%, 11 ± 3% and 8 ± 2% (p = NS) and distal segments by 13 ± 3%, 14 ± 4% and 15 ± 2% (p = NS) in control, variant angina and coronary artery disease groups, respectively.The results of this study indicate that rest baseline coronary tone and the vasomotor response of angiographically normal coronary artery segments to ergonovine and isosorbide dinitrate are similar in patients with noncardiac chest pain, Prinzmetal's variant angina and coronary artery disease. Evaluation of basal coronary artery diameter, therefore, is not useful for predicting the occurrence or location of coronary spasm.

Coronary artery spasm during cardiac angiography

Unexpected occurrence of coronary artery spasm is sometimes observed during cardiac catheterization. We report here two cases of coronary artery spasm with hypotension and urticaria subsequent to administration of contrast material. The etiology of coronary artery spasm is discussed.

Histamine-induced spasm not significantly modulated by prostanoids in a swine model of coronary artery spasm

The role of prostanoids in a swine model of coronary artery spasm was examined. Eighteen miniature pigs underwent endothelial denudation of the left coronary artery (left circumflex branch in 14 pigs and left anterior descending branch in 4 pigs) followed by high cholesterol feeding. Three months after the denudation, when coronary artery spasm was repeatedly provoked along the denuded portion of the coronary artery by histamine, the vasoconstrictive effect of thromboxane A2 and the preventive effects of indomethacin and prostacyclin against histamine-induced coronary artery spasm were examined. Intracoronary administration of thiothromboxane A2, 200 micrograms, a stable thromboxane A2 analog, failed to provoke coronary artery spasm (seven of seven cases) but nonselectively constricted the coronary artery by 33%. Intravenous administration of indomethacin, 2 mg/kg, or continuous intravenous infusion of prostacyclin, 50 ng/kg per min, failed to prevent histamine-induced coronary artery spasm (four of four and eight of eight cases, respectively), yet the spasm was all but prevented by intravenous pretreatment with diphenhydramine at a dose of 1 mg/kg. Thus, in this swine model, prostanoids may not play a primary role in the occurrence of coronary artery spasm.

Coronary artery spasm induced in atherosclerotic miniature swine.

Angiographically demonstrable coronary artery spasm could be provoked repeatedly by giving intracoronary or intravenous injections of histamine to miniature swine with experimentally induced atherosclerotic lesions of the coronary artery. The spasm induced in this way subsided either spontaneously or after the administration of nitroglycerin and was prevented by a calcium antagonist or an agent that blocks histamine H1 receptors. This model, which suggests that atherosclerotic changes may be one of the primary factors in the occurrence of coronary artery spasm, should facilitate studies on the pathogenesis of this condition.

Bypass Surgery for Prinzmetal Variant Angina

To the Editor. —A recent article in theArchivesrecommending bypass surgery for Prinzmetal angina deserves some comment (Bentiviglio et al, 136:313-316, 1974). Though localized stenosis of the coronary arteries 1 is frequently demonstrated in variant as well as in classic angina, the additional occurrence of coronary artery spasm has been sometimes documented in variant angina pectoris. 2-4 Likewise, coronary artery spasm has been documented in patients with variant angina and angiographically normal coronary arteries. 5 The hemodynamic changes occurring with variant angina appear to differ from those occurring with classic angina. Patients with classic angina commonly exhibit an increase in the pressure-time index prior to spontaneous or induced angina. In contrast, patients with variant angina frequently do not exhibit an increase in the pressure-time index; in fact, it often falls during pain. These findings suggest that, at least in some cases of variant angina, the pain may be