Novel rat model reveals important roles of β-adrenoreceptors in stress-induced cardiomyopathy.
BACKGROUND
Stress-induced cardiomyopathy (SIC), also known as Takotsubo cardiomyopathy, is an acute cardiac syndrome with substantial morbidity and mortality. The unique hallmark of SIC is extensive ventricular akinesia involving apical segments with preserved function in basal segments. Adrenergic overstimulation plays an important role in initiating SIC but the pathophysiological pathways and receptors involved are unknown.


METHODS
Sprague Dawley rats (~300 g) were injected with a single dose of the β-adrenergic agonist isoprenaline (ISO, i.p.) and echocardiography was used to study cardiac function. The akinetic part of the left ventricle was biopsied in six SIC patients. Amount of intracellular lipid and glycogen as well as degree of permanent cardiac damage were assessed by histology.


RESULTS
In rats, ISO at doses ≥ 50 mg/kg induced severe SIC-like regional akinesia that completely resolved within seven days. Intracellular lipid content was higher in akinetic, but not in normokinetic myocardium in both SIC patients and rats. β2-receptor blockade or Gi-pathway inhibition was associated with less widespread akinesia and low lipid accumulation but significantly increased acute mortality.


CONCLUSIONS
We provide a novel rat model of SIC that supports the hypothesis of circulating catecholamines as initiators of SIC. We propose that the β-adrenoreceptor pathway is important in the setting of severe catecholamine overstimulation and that perturbations of cardiac metabolism occur in SIC.
Wallenberg Laboratory at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Yangzhen
Y
Shao
Bjorn
B
Redfors
Margareta
M
Scharin Täng
Helge
H
Möllmann
Christian
C
Troidl
Sebastian
S
Szardien
Christian
C
Hamm
Holger
H
Nef
Jan
J
Borén
Elmir
E
Omerovic
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001706:Biopsy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage / Q000627:therapeutic use*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D054549:Takotsubo Cardiomyopathy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol
Gi-protein pathway, myocardial metabolism; Rat model; Stress-induced cardiomyopathy (SIC); Takotsubo cardiomyopathy; β-adrenoreceptors (β-ARs)