Allergic myocardial infarction.

In the literature there are very few well-documented cases of myocardial ischemia with pathomechanism accompanying allergic reaction. It is defined as Kounis syndrome, i.e. angina pectoris or infarction with allergic etiology. It is suggested, that few few cases of myocardial ischemia after a Hymenoptera sting reported thus far represent only a minute percentage of the total number of allergic reactions which occur in the circulatory system. It is difficult to make a credible decision whether allergic mechanisms are responsible for a greater number of deaths than we suspect. In the light of the literature, this review deals with current views regarding pathomechanisms of myocardial ischemia in the course of anaphylactic reaction and presents the clinical manifestation of myocardial ischemia with an allergic background, pointing out that allergic reactions involving cardiac muscle are not limited to the development of ischemia. The term organ anaphylaxis, in relation to the heart, also comprises rhythm and contractility disturbances which are present after exposure to the allergen. At the same time, the authors touch upon therapeutic aspects of immunotherapy in patients with significant cardiovascular risk and draw attention to the possibility of an alternative treatment for patients with allergic history, not only during desensitization but also for long-term outpatient treatment.

Type I CD36 deficiency associated with metabolic syndrome and vasospastic angina: a case report.

A 54-year-old man was admitted to our hospital for evaluation of chest pain occurring at rest in the morning. ST segment depression was observed during a treadmill exercise test. Coronary angiography identified spontaneous spasm of the proximal right coronary artery, and right coronary obstruction was improved from 90% to about 50% stenosis after intracoronary administration of nitroglycerin. Myocardial iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid uptake was absent, but thallium-201 uptake during single photon emission computed tomography was normal, and neither platelet nor monocyte expression of the CD36 molecule was observed, indicating type I CD36 deficiency. High blood pressure, elevated plasma triglyceride and fasting plasma glucose levels, and low high-density lipoprotein values suggested metabolic syndrome. The final diagnosis was type I CD 36 deficiency associated with metabolic syndrome and vasospastic angina.

Circulating T-lymphocyte activation in patients with variant angina.

BACKGROUND: Both experimental and pathological studies suggest that immune response and inflammation may play an important role in the pathogenesis of coronary spasm. DESIGN: To elucidate the role of systemic immune and inflammatory responses in the pathogenesis of coronary spasm, we studied circulating T-lymphocyte activation in variant angina patients (VAPs), stable effort angina patients (EAPs) and in control participants. METHODS: Twenty documented VAPs, 13 EAPs and 20 control participants were studied. To evaluate T-lymphocyte activation, T-lymphocyte surface antigen expression, including CD3, CD4, CD8 and HLA-DR, was measured by two-colour flow cytometric analysis. Serum-soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) were also measured by enzyme-linked immunosorbent assay. We restudied 10 of the VAPs to investigate the relationship between the disease activity of variant angina and T-lymphocyte activation. RESULTS: The percentage of CD3+/DR+ T-lymphocytes in VAPs (14.8%) was significantly higher than in EAPs (10.7%, P < 0.05) and control participants (9.7%, P < 0.005); however, levels of sIL-2R were the same among the three groups. Levels of CRP were within normal range in all VAPs. The percentage of CD8+/DR+ T-lymphocytes was significantly higher in VAPs (9.5%, P < 0.005) than in EAPs (5.5%) and control participants (5.9%), whereas the percentage of CD4+/DR+ T-lymphocytes was similar among the three groups. The percentage of activated T-lymphocytes in VAPs was unchanged during the follow-up period (mean intervals, 10 months). CONCLUSIONS: These results indicate that the chronic activation of T-lymphocytes, especially CD8+ T-lymphocytes, may be involved in the pathogenesis of coronary spasm.

Increased autoantibodies against oxidized low-density lipoprotein in coronary circulation in patients with coronary spastic angina.

Oxidized low-density lipoproteins are important in the progression of atherosclerosis. Autoantibodies against malondialdehyde-modified low-density lipoproteins have been reported to be predictive of the progression of atherosclerosis. This study sought to examine whether plasma levels of autoantibodies against oxidized low-density lipoprotein increase in the coronary circulation in patients with coronary spastic angina. The authors examined plasma antioxidized low-density lipoprotein antibody levels (activity unit values (AcU)/mL) simultaneously in the coronary sinus and the aortic root in 20 patients with coronary spastic angina, 23 patients with stable exertional angina, and 15 control subjects by measuring plasma levels of immunoglobulin G (IgG) autoantibodies against malondialdehyde-modified low-density lipoproteins by enzyme-linked immunosorbent assay. The plasma antioxidized low-density lipoprotein antibody levels (AcU/mL) in the coronary sinus increased in coronary spastic angina (38 +/- 16) compared with stable exertional angina (23 +/- 7) and control subjects (20 +/- 6) (p < or = 0.0001). The levels (AcU/mL) in the aortic root also increased in coronary spastic angina (33 +/- 12) compared with stable exertional angina (23 +/- 7) and control subjects (20 +/- 6) (p < 0.005). Furthermore, the coronary sinus-arterial differences of the levels (AcU/mL) were also higher in coronary spastic angina (5 +/- 9) than in stable exertional angina (0 +/- 6) and healthy subjects (-1 +/- 5) (p < 0.05). The generation of malondialdehyde-modified low-density lipoproteins is reported to be associated with atherothrombosis. These findings suggest that elevated levels of autoantibodies against malondialdehyde-modified oxidized low-density lipoproteins in coronary circulation are associated with the development of atherothrombosis from the progression of atherosclerosis rather than with the extent of coronary atherosclerosis in patients with coronary spastic angina.

HLA antigens in patients with variant angina in Japan.

There have been few reports on examining the susceptibility of variant angina. Accordingly, the major histocompatibility complexes (HLA-A, -B, -C, -DR) of unrelated Japanese patients with variant angina were examined. There were no significant differences in the frequency of HLA-A,-B, -C, and -DR antigens between patients and controls (n = 100). Although endothelial dysfunction with pathological abnormalities is suggested to be one of the etiological factors in vasospasm, immunogenetic abnormalities linked to HLA system might not play a role in the pathogenesis of variant angina.

Familial evidence of vasospastic angina and possible involvement of HLA-DR2 in susceptibility to coronary spasm.

An association between genetic factors and susceptibility to coronary spasm has not been proven. Because we encountered 7 patients with familial occurrence of vasospastic angina (VSA) in 3 families, the association of a genetic factor with coronary spasm was assumed. HLA typing as one of the genetic markers was performed in the 3 families, and the affected members in each family were found to share a HLA haplotype, carrying both HLA-DR52 and DQ6. This raised the possibility that one of the susceptibility genes for coronary spasm is located in the HLA region. To assess this possibility, HLA typing was performed and compared in 110 patients with VSA but without a family history of VSA (VSA group) and 55 patients with chest pain syndrome (CPS group) as control subjects. All patients underwent a provocation test for coronary spasm, and spasm was angiographically documented in the VSA group but not in the CPS group. Of all HLA antigens, the frequency of only HLA-DR2 was significantly higher in the VSA group than in the CPS group (39.1% vs 18.2%, p<0.01). The result implied that HLA-DR2 is in linkage disequilibrium with a susceptibility gene of VSA and thus is possibly involved in susceptibility to coronary spasm in some patients with VSA.

Coronary spasm, prostaglandin and HLA factors.

To elucidate the contribution of prostanoids in coronary spasm, plasma levels of thromboxane B2 (TXB2) and 6-keto PGF1 alpha at the coronary sinus and ascending aorta in 21 patients with variant angina were measured, as compared with findings in 20 with effort angina and 13 subjects with normal coronaries. In the coronary sinus blood, plasma TXB2 in patients with effort angina exhibited statistically significant high levels, as compared with data in the controls. On the contrary, the data obtained from patients with variant angina were not statistically significant. However, eight patients whose coronary angiogram revealed more than 50% of coronary stenoses had statistically significant high levels of TXB2 and other patients with normal coronaries or less than 50% of narrowing showed almost the same levels of TXB2 as the controls. In contrast to TXB2, the plasma levels of 6-keto PGF1 alpha in patients with variant angina were very low in both groups with variant angina. These data suggest that high levels of TXB2 observed in patients with atherosclerotic coronaries may be an accelerating factor while low levels of prostacyclin may be an essential factor leading to spasm. HLA analysis of 23 patients with variant angina was performed to search for genetic factors, under the hypothesis that such may contribute to the low levels in prostacyclin. This preliminary study revealed statistically significant high frequencies of Bw52 and B-40 in the patients, as compared with frequencies among 152 normal Japanese. Genetic studies are ongoing in our clinic.