Cardiovascular Diseases & Diagnosis

Segmental Arterial Mediolysis: A Review of a Proposed Vascular Disease of the Peripheral Sympathetic Nervous System – A Density Disorder of the Alpha-1 Adrenergic Receptor?

Abstract

Richard E. Slavin

Segmental arterial mediolysis (SAM) is an uncommon arteriopathy that causes catastrophic abdominal hemorrhages, ischemic vascular changes and organ injury. Morphologic changes have suggested that SAM is a vasospastic disorder and that the responsible pressor agent is norepinephrine. This premise was strengthened by the finding of SAM in greyhound dogs administered ractopamine, a Beta-2 agonist capable or releasing norepinephrine from the peripheral sympathetic nervous system. This article will fortify this hypothesis by fitting the morphologic features and clinical presentations of SAM into events occurring in a stimulated peripheral sympathetic reflex arc. SAM is activated by non-physiological stimuli supplied by indirect acting sympathomimetic agonists. The stimulus is discrete usually limited to one vascular bed. A possible excessive quantity of norepinephrine is released which combines with hyper dense areas of alpha-1 adrenoceptors on the cell membranes of the medial smooth muscle. The alpha-1 adrenoceptor density is in a dynamic state influenced by a variety of exogenous and endogenous factors such as age, sex and prior exposure to sympathomimetic agonists all important components of SAM’s clinical presentation. There is a plasticity to these hyper dense areas accounting for the variable targeting of SAM in the stimulated arterial bed. The hyper dense zones of conformed alpha-1 adrenceptor intensely activates the smooth muscle intracellular Gq heterotrimeric protein setting into motion a perturbed cascade of biochemical events directed to causing vasoconstriction. These events create SAM’s pathology by 1) overloading the cytoplasm with Ca2+ causing mitochondrial dysfunction that terminates in mediolysis and/or apoptosis, 2) launching a powerful vasoconstrictive response that shears the outer media from the adventitia and 3) inaugurating an exaggerated reparative response that may angiographically resolve injurious arterial lesions or create sequelae including fibromuscular dysplasia. In conclusion evidence garnered from clinical and morphologic findings in SAM support the hypothesis that SAM represents a disorder of the peripheral sympathetic nervous system effectuated by a hyper density of the alpha-1 adrenoceptor.