Dear Colleagues,

The pathophysiological mechanisms of anaphylaxis are still under investigation. Despite intensive research produced by different groups at the international level, these mechanisms are still poorly understood. The role of pre-formed and neo-formed mediators in the onset of anaphylactic shock has been well explored, but their involvement at the cellular level remains to be clearly defined. The primum movens for the onset of anaphylaxis is an intense vasodilation responsible for the onset of shock and then respiratory and cardiac damage responsible for death with multiorgan dysfunction in very severe clinical manifestation.

Histamine is the main preformed mediator responsible for the occurrence of bronchospasm induced by bronchoconstriction leading to severe acute asthma responsible for acute respiratory failure. It is also responsible for vasodilation through stimulation of intracellular adenylate cyclase activating nitric oxide (NO) synthase leading to the production of NO, a potent vasodilator. However, our previous results do not confirm the benefit of inhibitors of NOS on anaphylactic shock published by other groups. In this Special Issue, a detailed focus on the current knowledge of the role of NO is proposed. The role of prostaglandins and leukotrienes, mediators neo-formed from the cellular membrane is suspected in the occurrence of anaphylactic shock. Our group recently showed that voltage-dependent potassium channels are probably involved in the onset of vasodilation responsible for anaphylactic shock. The role of another potent vasodilator mediator, hydrogen disulfide (H2S), remains to be demonstrated. In this Special Issue, we propose the presentation of our promising results on the inhibition of enzymes producing H2S which restores blood pressure. The mechanisms of hypovolemia linked to plasma transudation by disruption of cell junctions will also be discussed. Finally, the genomic mechanisms of the production of many mediators will be discussed in a systematic review of the literature.

Prof. Dr. Abdelouahab Bellou
Prof. Dr. Paul Michel Mertès
Guest Editors

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• anaphylaxis
• allergy
• immunology
• emergency medicine
• animal models

Article 1: Combined treatment with K_V channel inhibitor 4-aminopyridine and either g-cystathionine lyase inhibitor ß-cyanoalanine or epinephrine restores blood pressure, increases serum vasoconstrictor levels, and improves survival in the Wistar rat model of anaphylactic shock
Authors: Abdelouahab Bellou, MD, PhD, MSc^{1,2, 3, 4}*^,§; Nacira Sennoun, PhD^5§; Elhadi H. Aburawi MD, PhD^3,§; Seth L. Alper, MD, PhD⁶; Ibrahim Abdallah Alfaki PhD⁷; Javed Yasin, PhD⁸ Subramanian Sekar, MPhar^9,10; Mohamed Shafiuallah, MSc⁹; Suhail Alsalam, MD, PhD¹¹; Abderrahim Nemmar, PhD⁹; Elsadig Kazzam, MD, PhD⁸; Paul Michel Mertes, MD, PhD, MS¹²; Suleiman Alhammadi, MD^3,*

Article 2: Effect of protein Kinase C activation in hypotension and survival in a Wistar rat anaphylactic shock model
Authors: Fayez Alshamsi¹, MD; Elhadi Aburawi², MD, PhD (co-first author and co-corresponding author), Taoufik Zoubeidi³, PhD; Seth Alper⁴ MD, PhD; Javed Yasin¹, PhD; Richardjayaraj Lawrencejayaraj², PhD; Mohamed Shafiuallah⁵, MSc; Abderrahim Nemmar⁵, PhD;  Souhail AlSalam⁶, MD, PhD; Sekar Subramanian^5,7, MPhar; Abdelouahab Bellou^8,9,10 MD, PhD (co-first author and corresponding author)

Article 3: Impaired cardiac mitochondrial function in an experimental model of anaphylactic shock
Authors: Walid Oulehri ^1,3, Olivier Collange ^1,3, Charles Tacquard ^1,3, Anne-Laure Charles ^2,3, Bernard Geny ^2,3, Paul Michel Mertes ^1,3,*

Article 4: Role of the Nitric Oxide inhibition in the evolution of anaphylactic shock in animal models: A systematic Review
Authors: Maryam Alfalasi¹; Sarah Alzaabi¹ (co-first author);  Elhadi Aburawi² (co-first author and co-corresponding author); Linda Östlundh³; Paul Michel Mertes⁴; Abdelouahab Bellou^5,6,7,8 (co-first author, corresponding author). Article 5: Suhail Abdallah et al. Pathology and immunopathology of anaphylactic shock

Article 5: Role of anaphylactic shock mediators in anaphylactic shock
Authors: Paul Michel Mertes^1,2 and Abdelouahab Bellou^3,4,5

Article 6: Role of potassium channels in anaphylactic shock: A comprehensive narrative review
Authors: Abdelouahab Bellou^1,2,3,*, Elhadi Aburawi⁴, Linda Östlundh⁵

Article 7: Pathology and Immunopathology of anaphylactic shock
Authors: Suhail Alsalam^1,*, Ehadi Aburawi², Abdelouahab Bellou^3,4,5

Article 8: Genomic approach for the understanding of the pathophysiology of anaphylaxis
Author: Bernard Bihain

Article 9: A new inhibitor of potassium voltage dependent channels, the 3,4,5 aminopyridine improves the hypotension and survival in a Wistar rat anaphylactic shock model.
Authors: Richardjayaraj Lawrencejayaraj¹; Elhadi H. Aburawi¹; Taoufik Zoubeidi²; Javed Yasin³; Mohamed Shafiuallah⁴; Seth L. Alper⁵; Suhail Alsalam⁶; Paul Michel Mertes^7,8; Abdelouahab Bellou^9,10,11,*

Article 10: Analysis of the expression of the genes involved in the inflammation and the vasodilation induced in a Wistar rat model of anaphylactic shock
Authors: Abdelouahab Bellou^1,2,3,*; Seth Alper⁴; Bernard Bihain⁵; Richardjayaraj Lawrencejayaraj⁶; Starling Emerald Bright David⁷; Elhadi Aburawi⁶