Kounis syndrome has been established as a hypersensitivity coronary disorder induced by various conditions, drugs, environmental exposures, foods and coronary stents. Allergic, hypersensitivity, anaphylactic and anaphylactoid reactions are associated with this syndrome. Vasospastic allergic angina, allergic myocardial infarction and stent thrombosis with occluding thrombus infiltrated by eosinophils and/or mast cells constitute are the three reported, so far, variants of this syndrome. Apart from coronary arteries, it affects the cerebral and mesenteric arteries. Its manifestations are broadening and its etiology is continuously increasing. Kounis syndrome is a ubiquitous disease which represents a magnificent natural paradigm and nature's own experiment in a final trigger pathway implicated in cases of coronary artery spasm and plaque rupture. Kounis syndrome seems to be not a rare disease but an infrequently diagnosed clinical entity which has revealed that the same mediators released from the same inflammatory cells are also present and in acute coronary events of non allergic etiology. These cells are not only present in the culprit region before plaque erosion or rupture but they release their contents just before an actual coronary event. Therefore, awareness of etiology, epidemiology, pathogenesis and clinical manifestations seems to be important for its prognosis, diagnosis, treatment, prevention.

https://www.degruyter.com/downloadpdf/j/cclm.2016.54.issue-10/cclm-2016-0010/cclm-2016-0010.xml

Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management

Coronary Hypersensitivity Disorder: The Kounis Syndrome

Markers of anaphylaxis – a systematic review

Profound bradycardia caused by sugammadex has been reported, although its mechanism is unclear. Herein, we suggest a possible culprit for this phenomenon. A 50-year-old woman without comorbidity except mild obesity underwent a transabdominal hysterectomy and right salpingo-oophorectomy. After surgery, sugammadex 200 mg was intravenously administered. Approximately 4 min later, her heart rate decreased to 36 bpm accompanied by hypotension (41/20 mmHg) and ST depression in limb lead electrocardiogram (ECG). Atropine 0.5 mg was injected intravenously without improving the hemodynamics. Intravenous adrenaline 0.5 mg was added despite the lack of signs suggesting allergic reactions. Her heart rate and blood pressure quickly recovered and remained stable thereafter, although 12-lead ECG taken 1 h later still showed ST depression. In this case, the significant bradycardia appeared attributable to coronary vasospasm (Kounis syndrome) induced by sugammadex, considering the ECG findings and high incidence of anaphylaxis due to sugammadex.

/pdf/a-rare-case-of-atropine-resistant-bradycardia-following-53s3ptxa74.pdf

A rare case of atropine-resistant bradycardia following sugammadex administration.

https://doi.org/10.1016/j.biopha.2022.112843

Epidemiology, clinical ramifications, and cellular pathogenesis of COVID-19 mRNA-vaccination-induced adverse cardiovascular outcomes: A state-of-the-heart review

Anaphylaxis-induced hyperfibrinogenolysis and the risk of Kounis syndrome: the dual action of tryptase.

Acute Myocardial Infarction Within 24 Hours After COVID-19 Vaccination: Is Kounis Syndrome the Culprit?

To the Editor: In the very interesting clinical report published in your journal [1], a patient who had been previously hospitalized for a right hemicolectomy for colon cancer and was readmitted for thoracotomy and resection of a right upper lobe lung mass developed, during anesthesia, coronary artery spasm and severe shock followed by a second shock with severe bronchospasm and hypotension 4 weeks later. Although flushing or urticaria was not observed during both surgeries, tryptase levels were measured and found elevated in the second surgery. The authors of this report thought that remifentanil was the trigger of these manifestations. However, they did not refer to possible intracoronary mast cell activation [2], which sometimes is not clinically evident, but still induces the release of vasospastic, thrombogenic, and plaque-rupturing agents, including measurable serum tryptase. The described patient had a history of hypertension with a previous surgical intervention. During general anesthesia the patient received five anesthetic drugs, namely, fentanyl, propofol, rocuronium, sevoflurane, and again remifentanil, one antibiotic, cefuroxime, and during the following resuscitation, epinephrine intravenously. Four weeks following the first anesthesia, the patient was subjected to a second surgery with the same drugs but with the addition of hydrocortisone. All these agents are known to be capable of inducing mast cell degranulation [3]. It is well known that mast cell degranulation is initiated by antigens cross-bridging their corresponding, receptorbound antibodies on the mast cell or basophil cell surface. These cells degranulate and release their mediators when the critical number of bridged antibodies reaches the critical order of 2,000. It might be possible to accumulate the critical number of bridges by more than one non-crossreactive antigen and its corresponding antibody. Sensitive patients simultaneously exposed to several antigens have more symptoms than do mono-sensitized individuals. A recent study reported that antibodies with different specificities can have an additive effect, and even small amounts of corresponding antigens can trigger mediator release when the patient is simultaneously exposed to them [4]. These data suggest that a possible sensitization to one anesthetic drug should not be clinically evaluated as a consequence of exposure to a single drug but rather viewed in the context of potential sensitization to multiple anesthetic agents. Kounis syndrome [2] is the concurrence of acute coronary syndromes with conditions associated with mast cell degranulation. It is caused by inflammatory mediators such as histamine, neutral proteases, arachidonic acid products, platelet-activating factor, and a variety of cytokines and chemokines released during the activation process. It seems possible that the described patient suffered a type I variant of Kounis syndrome, which is seen in patients with normal coronary arteries but with no predisposing factors for coronary artery disease, in whom the acute release of inflammatory mediators can induce either coronary artery spasm without increase of cardiac enzymes and troponins, or coronary artery spasm progressing to acute myocardial infarction (MI) with increased cardiac enzymes and troponins. On the other hand, type II variant of Kounis syndrome includes patients with culprit but quiescent preexisting atheromatous disease, in whom the acute release of N. G. Kounis (&) G. G. Tsigkas G. Almpanis S. N. Kouni G. N. Kounis A. Mazarakis Department of Cardiology, University of Patras Medical School, Rio, Patras, Greece e-mail: ngkounis@otenet.gr

Suspected recurrent anaphylaxis in different forms during general anesthesia : implications for Kounis syndrome

Therapies - Sous presse. Epreuves corrigees par l'auteur. Disponible en ligne depuis le lundi 26 fevrier 2018

Sophia N. Kouni

Papers

Anaphylaxis-induced hyperfibrinogenolysis and the risk of Kounis syndrome: the dual action of tryptase.

Acute Myocardial Infarction Within 24 Hours After COVID-19 Vaccination: Is Kounis Syndrome the Culprit?

Suspected recurrent anaphylaxis in different forms during general anesthesia : implications for Kounis syndrome

Beware of an allergic reaction in stented patients: Amoxicillin/clavulanic acid anaphylaxis associated with fatal Kounis syndrome and stent thrombosis