Foods, Drugs and Environmental Factors: Novel Kounis Syndrome Offenders.

Kounis syndrome is hypersensitivity coronary disorder induced by various types of environmental exposures, drugs, conditions and stents. Allergic, hypersensitivity, anaphylactic and anaphylactoid reactions are associated with this syndrome. The disorder manifests as coronary spasms, acute myocardial infarction and stent thrombosis and affects the cerebral and mesenteric as well as coronary arteries. Importantly, its manifestations are broad and its etiology is continuously increasing. Recently, a variety of unusual etiologies have been reported including Anisakis simplex, scombroid syndrome, the use of Gelofusin or ultrasound contrast agents, kiwifruit, fly bites, and bee stings. Furthermore, losartan and the paradox of corticosteroid allergy have been implicated as possible causes. Although not rare, Kounis syndrome is infrequently diagnosed. Therefore, awareness of its etiology, manifestations and pathophysiology is important for providing the proper diagnosis and treatment and determining prognosis.

Bee and wasp stings: reactions and anaphylaxis.

This article provides a brief introduction to the history of anaphylaxis and the order Hymenoptera, which is responsible for most reported sting-induced allergic reactions. The anatomic similarities and differences as well as inhabited similarities and differences between bees and wasps are discussed. The various types of allergic reactions and their manifestations are described. Treatment regimens ranging from home therapies and over-the-counter medications to prescription medications and emergency treatments are introduced. Education, avoidance, and venom-specific immunotherapy are discussed.

Suspected recurrent anaphylaxis in different forms during general anesthesia.

We report on a patient who presented with recurrent severe shock during general anesthesia. The patient was a man scheduled for lung surgery whose first attack was a coronary spasm, which was followed by a second shock with severe bronchospasm and hypotension 4 weeks later. An elevated serum tryptase concentration was observed, and subsequent skin testing revealed negative reactions to some drugs administered in this case. This case serves to alert anesthetists to the possibility of some different forms of allergy and highlights the importance of rigorous investigation of all the reagents and phenomena.

Hymenoptera sting-induced Kounis syndrome: effects of aspirin and beta-blocker administration.

Kounis syndrome is the concurrence of acute coronary syndromes with conditions associated with activation of interacting inflammatory cells including allergic or hypersensitivity and anaphylactic or anaphylactoid insults. It is caused via inflammatory mediators released during inflammatory cell activation. A variety of conditions, drugs, and environmental exposures can induce Kounis syndrome. A patient suffering from coronary artery disease and taking metoprolol and aspirin was stung by wasps and developed cutaneous allergic signs including rash, urticaria and orbital oedema. This was followed by retrosternal pain, chest discomfort and electrocardiographic changes compatible with acute myocardial ischemia. Cardiac enzymes, troponins and blood pressure remained normal but serum tryptase was raised. The clinical implications and pathophysiology of this rare association are discussed.

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.

Cefuroxime-induced coronary artery spasm manifesting as Kounis syndrome.

Allergic angina and allergic myocardial infarction (Kounis syndrome) occurring during the course of a drug-induced allergic reaction in the absence of angiographically stenosed coronary arteries, is rare in clinical practice. This paper reports the case of a 70-year-old woman with no significant risk factors for coronary artery disease who developed coronary artery spasm after intravenous injection of cefuroxime. A subsequent coronary angiogram revealed normal coronary arteries (type I variant of the syndrome). The allergic reaction following cefuroxime administration seems to have triggered the development of coronary artery spasm. Susceptible individuals expressing an amplified mast cell degranulation effect may be more vulnerable to coronary artery spasm. The clinical implications of this syndrome are also discussed.

Coronary spastic angina in patients with connective tissue disease.

BACKGROUND: Connective tissue disease, which is an inflammatory condition represented by C-reactive protein (CRP), is a risk factor for ischemic heart disease. The aim of the present study was to examine if there is a relationship between connective tissue disease and coronary spastic angina, and whether the inflammatory condition was associated with ischemic heart disease, even in patients with connective tissue disease. METHODS AND RESULTS: The study group comprised 73 consecutive patients with connective tissue disease who were admitted to the Department of Cardiovascular Medicine between April 2000 and March 2003. Of the 73 patients, 38 (19 men, 19 women) were diagnosed as having an ischemic heart disease (7 patients acute coronary syndrome, 19 patients coronary spastic angina, 12 patients stable exertional angina). In the present study, 19 (50.0%) of the 38 patients of ischemic heart disease were diagnosed as having coronary spastic angina. In the same study period, 151 (38.7%) of 390 patients with ischemic heart disease (without connective tissue disease) were diagnosed as having coronary spastic angina. The frequency of the patients with coronary spastic angina tended to be higher in patients with connective tissue disease than in patients without connective tissue disease. Among the study patients, serum CRP concentrations (mg/dl) were higher in patients with acute coronary syndrome (1.50 +/- 1.19, n=7) and those with coronary spastic angina (1.06 +/- 1.78, n=19) than in those with non-ischemia (0.35 +/- 0.40, n=35, p<0.05). CONCLUSIONS: Coronary spastic angina is a frequent complication in patients with connective tissue disease and the inflammatory condition is associated with coronary spastic angina and unstable angina in patients with connective tissue disease.

Preference toward a T-helper type 1 response in patients with coronary spastic angina.

BACKGROUND: Coronary artery spasm plays an important role in the pathogenesis of ischemic heart diseases such as unstable angina (UA) and acute myocardial infarction. Nitric oxide (NO) plays an important role in coronary artery spasm. We previously reported a deficiency in NO activity in the spasm arteries of patients with coronary spastic angina (CSA). Others have reported that NO influences the immune response. Therefore, we investigated the balance between T-helper type 1 (Th1) and 2 (Th2) responses in patients with CSA by evaluating the frequencies of interferon (IFN)-gamma-producing T cells and interleukin (IL)-4-producing T cells in the peripheral blood of such patients. METHODS AND RESULTS: Peripheral blood mononuclear cells were collected from 50 consecutive patients with CSA, 23 consecutive patients with UA, 36 patients with stable angina (SA), and 21 patients with chest pain syndrome (CPS). Cytokine-producing CD4+ T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA and CSA were associated with a significant increase in the frequency of CD4+ T cells that produced IFN-gamma, whereas these conditions caused no significant difference in the frequency of CD4+ T cells that produced IL-4. Culturing with an NO donor compound for 24 hours before stimulation inhibited the increase in the frequency of CD4+ T cells that produced IFN-gamma. CONCLUSIONS: We demonstrated that there was a preference toward the Th1-type response in patients with CSA and that T cells showed a reduced Th1-type response after being treated with NO.

Coronary atherosclerosis and oxidative stress as reflected by autoantibodies against oxidized low-density lipoprotein and oxysterols.

Clinical studies and animal experiments have demonstrated that oxidized low-density lipoprotein (oxLDL) and oxysterols play important roles in atherogenesis. OxLDL is immunogenic, and autoantibodies (Ab) against oxLDL are detectable in serum. We investigated the relevance of oxysterols and Ab against-oxLDL to coronary artery disease (CAD) in 183 patients undergoing coronary angiography. Patient groups included angiographically normal subjects (< 75% stenosis), others with spasm (> 75% narrowing in response to acetylcholine), and some others with fixed stenosis (> 75%). The group with stenosis was subdivided into patients with stable and unstable angina. Serum concentrations of autoantibodies and 25-, 27-, and 7-beta-hydroxycholesterols were significantly higher in the stenotic group than in the normal group (P < 0.01, P < 0.05, P < 0.05, and P < 0.05, respectively). Antibodies, but not oxysterol concentrations, were significantly greater in subjects with unstable than with stable angina (P < 0.01). We conclude that anti-oxLDL antibody and oxysterol concentrations are associated with coronary artery stenosis, and that oxidative stress may be greatly increased in unstable angina.

Endothelial nitric oxide synthase gene mutation and human leukocyte antigen analyzed in three cases of familial vasospastic angina pectoris.

A 50-year-old woman with rest angina underwent cardiac catheterization; coronary angiography in the presence of acetylcholine revealed 99% coronary spasm of the proximal left anterior descending artery. The patient's 82-year-old mother was also admitted to hospital with rest angina. Her Holter electrocardiogram showed ST-segment elevation during the attack at rest and coronary angiography showed 99% spasm of the right coronary artery and 90% spasm of the left coronary artery. Both women complained of chest pain during the spasm, which was accompanied by ST-segment depression. The 62-year-old brother of the original patient was also found to have coronary spasm of the left coronary artery. Human leukocyte antigen was analyzed in the 2 women: A2, B51, CW1, DR8 and DQ1 were common factors. A Glu298Asp point mutation of the endothelial nitric oxide synthase gene was investigated in both parents, their 2 daughters and 2 sons, but was not detected in the 3 patients, and was detected only in the 90-year-old father who did not suffer from angina. Nor was the T-786-C mutation found in the 3 cases. Other causes of familial spasm need to be elucidated.

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.

Vasospastic angina in two sisters.

Vasospastic angina was observed in two sisters. The 52-year-old younger sister presented with rest angina at midnight and in the early morning. The coronary arteriogram showed no significant organic stenosis. Vasospasm to the left anterior descending and right coronary arteries was induced by the intracoronary administration of acetylcholine. The 57-year-old elder sister complained of rest and effort angina. Her coronary arteriogram was also normal. Vasospasm to the left circumflex and right coronary arteries was provoked by acetylcholine. In both cases, human leukocyte antigen DQw3 was negative. In the present cases, genetic factors may partly contribute to the mechanism of vasospastic angina.

[The correction of disorders in arachidonic acid metabolism in coronary spasm of an immune origin]. / Korektsiia porushen' metabolizmu arakhidonovoï kysloty pry koronarospazmi imunnoho henezu.

The effect of phosphocreatine and hydroxamate-linoleate (an inhibitor of lipoxigenase) on development of the pathologic process in coronary vessels with immune (cytotoxic) injury of the heart was studied in the experiments on narcotized dogs. Development of the immune response after administration of cardiac serum resulted in development of large transmural damage of the left ventricle myocardium, increased resistance of coronary vessels and changed coronary vascular reactions, which correlates with changes in arachidonic acid metabolism. Experimental data described in this report demonstrate the efficiency of membrane coronary vessels stabilization and inhibition of a lipoxygenase pathway in arachidonic acid metabolism in protection of immune damage of the heart and coronary vessels.

Coronary spasm in two sisters.

Coronary spasm was observed in two sisters. Neither of them had significant atheromatous stenosis in the coronary arteries. The 41-year-old elder sister presented with resting morning angina. The stress electrocardiogram showed marked depression of the ST-segment in precordial leads. Diffuse vasospasm in the left anterior descending artery was induced by the intracoronary administration of acetylcholine. The 38-year-old younger sister suffered from acute inferior myocardial infarction after taking methylergonovine following an abortion. Emergent coronary angiography disclosed a thrombus in the proximal right coronary artery which was dissolved with intracoronary administration of urokinase. There was no residual stenosis in the culprit vessel. Although the sisters do have risk factors for coronary spasm, an inherited factor may contribute to the mechanism of the spasm.