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

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]. This hypothesis was strengthened with the discovery of SAM in the large renal, intrahepatic and coronary arteries of greyhound dogs administered a single dose of ractopamine an agent used in animal husbandry for its repartitioning properties and illegally to enhance athletic ability in racing animals [11]. Ractopamine is a Beta-2 adrenergic agonist believed capable of releasing norepinephrine

Fatal hemoperitoneum due to segmental arterial mediolysis

“…Based on the morphologic changes, Slavin17 proposed that SAM is a vasospastic disorder due to hyperdense areas of alpha-1 adrenergic receptor on the membrane of the arterial medial smooth muscle cells. The hyperactivation of the muscle fibers promotes a cytoplasmic Ca + overload with consequent mitochondrial dysfunction, mediolysis, and/or apoptosis easing the detachment of the outer media from the adventitia.…”

Segmental arterial mediolysis with mesangial cell hyperplasia; A review with supplementary comments concerning its pathogenesis

“…The figures utilized in this article are derived from the multiple cases of SAM reported by the authors in references [1][2][3][4][5][6][7][8][9][10]. Their journal origins are listed in the figure descriptions.…”

“…This agent also can release norepinephrine from the peripheral nervous system. These findings led to the hypothesis that SAM represented a disease of the peripheral sympathetic nervous system principally induced by the administration of sympathomimetic agonists [10]. Norepinephrine as neurotransmitter in this system couples with the alpha-1 adrenoceptor aggregated on the cell membrane of the smooth muscle cells to induce a conformational change that enabled this receptor to activate a heterotrimeric G-protein.…”

“…Trans mural mediolysis with loss of the intima and internal elastica creates arterial gaps ( Figures 1 and 13) that dilate to form gap-aneurysms ( Figure 14). It is suspected that the stimulus induced by the agonists are intensified in zones of increased density of alpha-1 adrenoceptor distributed on the smooth muscle cell membranes [10]. This receptor is in a dynamic state and its density is augmented by factors such as age-increased in the Segmental arterial mediolysis with mesangial cell hyperplasia; A review with supplementary comments concerning its pathogenesis elderly, sex-elevated in premenopausal females and possibly also by previous exposure to sympathomimetic agents-all important clinical considerations in patients developing SAM [12,13].…”

“…These considerations militate against the simultaneous discovery of clinically expressed SAM, in its injurious phase, with a diagnosed pheochromocytoma. The episodic or continuous circulating supra-physiologic release of catecholamines by this tumor may "sensitize" the arterial smooth muscle by promoting movement of the alpha-1 adrenoceptors creating the hyper-dense areas that are believed instrumental for the development of SAM Segmental arterial mediolysis with mesangial cell hyperplasia; A review with supplementary comments concerning its pathogenesis [10]. The close proximity of the pheochromocytomas with its released circulating catecholamines to the celiac plexus could also expedite this sensitization.…”