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Segmental arterial mediolysis--an iatrogenic vascular disorder induced by ractopamine
Richard E Slavin1, Micheal J Yaeger
1Cascade Pathology Group, Legacy Emanuel Hospital and Health Center, Portland, OR 97227, USA. rslavin@lhs.org
Background:
Segmental arterial mediolysis, an uncommon arterial disorder most often occurring in the splanchnic muscular arteries of the abdomen, is a cause of catastrophic hemorrhages. Its histology and initial clinical presentations suggested that it represented a localized norepinephrine-induced vasospastic response to perturbations in vascular tone and blood volume distribution caused by coexisting vasoconstrictor conditions. However, later presentations were at odds with some aspects of this hypothesis.
Methods:
Nine greyhound dogs were administered a single dose of ractopamine. Two dogs developing persistent conduction abnormalities with biochemical evidence of heart injury were euthanized and necropsied--one 4 days and the other 17 days after dosage This report is based on findings and comparisons of the canine abdominal and coronary arteries to segmental arterial mediolysis.
Results:
Lesions having features of early-injurious-stage segmental arterial mediolysis were identified in the canine arteries 4 days postractopamine, and arteries examined after 17 days showed alterations typically occurring in reparative-stage segmental arterial mediolysis. It is suspected that ractopamine, a Beta-2 adrenergic agonist, created segmental arterial mediolysis by neuromodulating the peripheral sympathetic nervous system to release norepinephrine from varicosities of efferent nerves serving splanchnic arteries that stimulate alpha-1 receptors to induce injury at the adventitial medial junction and medial muscle apoptosis.
Conclusion:
This finding and other cited examples suggest that segmental arterial mediolysis may be a disorder principally caused by iatrogenic or accidental exposure to alpha-1 adrenergic receptor agonists or Beta-2 agonists able to release norepinephrine from the peripheral nervous system.
Insights
Segmental arterial mediolysis may be caused by alpha-1 or Beta-2 adrenergic agonists. Ractopamine, a Beta-2 agonist, induced lesions resembling this arterial disorder in dogs, suggesting a link to norepinephrine release.
Area of Science:
- Vascular pathology
- Adrenergic receptor pharmacology
- Animal models in cardiovascular research
Background:
- Segmental arterial mediolysis (SAM) is a rare arterial disorder affecting abdominal muscular arteries, often leading to severe hemorrhage.
- Previous hypotheses suggested SAM resulted from norepinephrine-induced vasospasm linked to vasoconstrictor conditions.
- However, some clinical presentations did not fully align with this initial hypothesis.
Purpose of the Study:
- To investigate the potential role of ractopamine, a Beta-2 adrenergic agonist, in inducing lesions similar to segmental arterial mediolysis.
- To explore the mechanism by which Beta-2 agonists might contribute to SAM, particularly concerning norepinephrine release and alpha-1 adrenergic receptor stimulation.
Main Methods:
- Nine greyhound dogs were administered a single dose of ractopamine.
- Two dogs with conduction abnormalities and heart injury were euthanized at 4 and 17 days post-administration for necropsy.
- Canine abdominal and coronary arteries were examined and compared to human SAM findings.
Main Results:
- Arterial lesions consistent with early-stage SAM were observed 4 days after ractopamine administration.
- Arteries from dogs examined 17 days post-administration showed features of reparative-stage SAM.
- Ractopamine is suspected to induce SAM by stimulating norepinephrine release from sympathetic nerves, leading to alpha-1 receptor activation and vascular injury.
Conclusions:
- Segmental arterial mediolysis may be primarily caused by exposure to alpha-1 adrenergic receptor agonists.
- Beta-2 agonists that trigger norepinephrine release from the peripheral nervous system are also implicated.
- This study suggests a potential iatrogenic or accidental cause for SAM related to specific adrenergic agonists.
