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

Richard E Slavin

doi:10.4172/2329-9517.1000190

Abstract

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.

Highlights

Calamitous abdominal hemorrhage is the hallmark presentation of segmental arterial mediolysis (SAM) an uncommon arteriopathy of the large and medium sized muscular arteries distributed in the abdomen, retroperitoneum, heart, and brain base
The morphologic alterations of fibromuscular dysplasia (FMD) in the arteries of the extremities in children do not closely resemble changes of reparative SAM [25]. These findings suggest that SAM is not the only cause of FMD
1: The morphologic features of SAM in the injurious phase are consistent with vasospasm and the responsible pressor agent is released at the adventitial-medial junction the site of the initial lesion in SAM. 2: Identified agents suspected of initiating SAM are iatrogenic introduced indirect acting sympathomimetic agonists capable of releasing norepinephrine from the varicosities on the post-ganglionic branches of sympathetic plexuses. 3: The ability of the sympathetic nervous system to undergo discrete activation is mirrored in SAM where the pattern of activation is primarily limited to one arterial bed

Summary

Introduction

Calamitous abdominal hemorrhage is the hallmark presentation of segmental arterial mediolysis (SAM) an uncommon arteriopathy of the large and medium sized muscular arteries distributed in the abdomen, retroperitoneum, heart, and brain base. Slavin and coworkers suspected that SAM represented a vasospastic disorder because of its segmental distribution and medial morphologic features and renamed it SAM a descriptive term drawn from its most characteristic morphologic features [4] They proposed that norepinephrine was the responsible pressor agent since the earliest lesions formed at the outer arterial wall the precise site where norepinephrine is produced in varicosities and released from the efferent sympathetic nerve fibers innervating the muscular arteries [5]. On the basis of these findings it was proposed that SAM was primarily an iatrogenic vascular disorder induced by alpha-1 adrenergic receptor agonists or Beta-2 agonists capable of releasing norepinephrine from the peripheral sympathetic nervous system [11]. This article will reinforce this hypothesis by matching SAM’s pathology and clinical presentations to features and biochemical events occurring in the stimulated peripheral sympathetic reflex arc

Materials and Methods

Conclusion