Original ArticleSegmental arterial mediolysis—an iatrogenic vascular disorder induced by ractopamine
Introduction
Segmental arterial mediolysis (SAM), an uncommon nonsystemic disease occurring at all ages, most often presents with sudden catastrophic hemorrhages in the abdominal cavity, in the retroperitoneum, or at the base of the brain. It is a disease of the muscular arteries in these locations and in the heart. The bleeding is caused by ruptured aneurysms fashioned from arterial gaps created by mediolysis and intimal loss and/or arterial dissections produced at the gap outer medial muscle interface or from granulation tissue formed as a reparative response to the tearing separation of the outer media from the adventitia [1], [2], [3], [4], [5].
SAM does not appear to be atherosclerotic, infectious, immunological, or congenital in origin. Slavin and coworkers have proposed that SAM represents a vasospastic disorder principally caused by norepinephrine [3], [4].
Recently, Yaeger et al. [6], in a study designed to detect the metabolites of ractopamine, a Beta-2 agonist in the urine of greyhounds, discovered a vascular lesion similar to SAM in renal, hepatic, and coronary arteries in dogs necropsied because they developed severe cardiac conduction irregularities with heart failure following the administration of this drug.
This article will describe the canine arterial lesion, compare it to SAM, and develop a hypothesis that implicates this and similarly acting drugs in the genesis of SAM.
Section snippets
Methods and materials
Nine greyhounds were administered ractopamine to investigate the ability to detect this compound and its metabolites in urine by a pari-mutuel testing laboratory. Each dog was given a single dose of 1 mg/kg of ractopamine orally.
Seven of nine dogs developed pronounced cardiac arrhythmias and had elevated troponin I levels. Rhythm abnormalities resolved in all but two dogs, one euthanized and necropsied 4 days postdosing and the second euthanized and necropsied 17 days after ractopamine
Arterial
The dog sacrificed 4 days following the administration of the ractopamine protocol exhibited lesions in the distal renal arteries and their hilar branches, large intrahepatic arteries and extramural coronary arteries and their large perforating branches. The arteries of the intestinal tract and brain were not examined. The pathologic alterations in all the involved arteries centered on the adventitial–medial junction where linear fibrin deposition and smooth muscle necrosis occurred. The fibrin
Discussion
Initial reports of cases of SAM indicated that SAM frequently arose in elderly patients with a background of one or more disorders associated with vasoconstriction [3]. This finding coupled with the SAM's morphologic characteristics—segmental distribution, resemblance to the fibrinoid necrolysis of malignant hypertension, vacuolar muscle alterations, and minimal reactive inflammatory changes—led Slavin and coworkers [2], [3], [4] to suspect that vasospasm was the cause of SAM. It was
Acknowledgments
The authors would like to thank John Levin for his invaluable help with the digital photography.
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2021, Cardiovascular PathologyCitation Excerpt :Segmental arterial mediolysis (SAM) is a rare, non-atherosclerotic, non-hereditary, and non-inflammatory arteriopathy which was proposed by Slavin and Gonzalez in 1976 [1]. It can involve muscular arteries such as intra-abdominal, coronary, and intracranial arteries [2,3]. Slavin et al. proposed four distinctive features of SAM: 1) lytic loss of medial muscle causes vacuolization; 2) separation between the media and the adventitia results in dissecting hematoma; 3) dilated arterial gaps rupture and form a pseudoaneurysm; and 4) reparative fibrosis and thrombi at the lesion cause stenosis and occlusion [1].
Cerebral segmental arterial mediolysis in a pediatric patient: A novel case
2020, Human Pathology: Case ReportsCitation Excerpt :Radiologically, these vascular modifications most frequently translate into dissections, aneurysms, beading, webs or occlusions that either stabilize or regress after a certain period of time. Although the pathophysiology of SAM is still unclear, a recent study points to an activation of vascular adrenergic receptors as a possible etiologic factor in the disease [9]. In pre-adults, rare perinatal cases of SAM have been described including one autopsy case with reported but undocumented CNS involvement in a preterm child [10].
A case of segmental arterial mediolysis with widespread involvement of cranial and abdominal arteries
2019, Journal of the Neurological SciencesTreatment of Ruptured Vertebral Artery Dissection and Abdominal Hemorrhage Associated with Segmental Arterial Mediolysis Using Endovascular Coil Embolization
2018, World NeurosurgeryCitation Excerpt :The etiology of SAM remains controversial. It has been posited that the condition may be a pathologic response to vasospasm, and it has been reported that the histologic patterns of the vasospasm similar to SAM can be induced using an epinephrine analog in a canine model.6,7 Vasospasms often arise as a complication of aneurysmal subarachnoid hemorrhage (SAH).
Segmental arterial mediolysis presenting as spontaneous bilateral renal artery dissection
2018, Radiology Case ReportsCitation Excerpt :Bleeding in the injurious phase occurs from gap junctions and in the reparative phase it occurs from fragile vessels of the granulation tissue between the outer media and adventitia [5,13]. Stenosis in the injurious phase is due to thrombus formation and overgrowth of the granulation tissue and plaques in the reparative phase [5,11,13]. Differential diagnosis of the renal infarcts and dissection include congenital conditions (Ehlers-Danlos, Marfan, Loeys-Dietz), vasculitis (Behçet disease, polyarteritis nodosa, neurofibromatosis), embolism, coagulation disorders, renal trauma (iatrogenic), infection (mycotic aneurysm and endocarditis), aortic dissection, atherosclerosis, FMD, and SAM [15].
Potentially stress-induced acute splanchnic segmental arterial mediolysis with a favorable spontaneous outcome
2017, Journal of Vascular Surgery Cases and Innovative TechniquesCitation Excerpt :First, a causative relationship between SAM and β2 agonist administration has been established through animal experiments. Slavin and Yaeger have demonstrated that the oral administration of a single dose of ractopamine, a β2-adrenergic agonist drug, induced SAM in greyhound dogs.4 Indeed, characteristic arterial lesions of the early injurious stage of SAM were observed 4 days after the administration of the β2 agonist, as were typical alterations of the reparative stage of SAM 17 days later.
Funding: none.