20. β2
β2
β2
β2
β2
β2
β1 β1
β1 β1
β1
β1
β1
Adrenaline – β2 – Gi signalling
NEGATIVELY INOTROPIC
ANTIAPOPTOTIC
Noradrenaline – β1 – Gs signalling
POSITIVELY INOTROPIC
PROAPOPTOTIC
= sympathetic nerve
Takotsubo Syndrome and the β2AR Hypothesis
Lyon AR et al Nat Clin Pract Cardiovasc Med 2008 5 (1): 22-29.
21. B 10 20 30 40 50 60
-40
-20
0
20
40
Apex
Adrenaline
Noradrenaline
A
%ΔFS
B 10 20 30 40 50 60
-40
-20
0
20
40
B
Mid LV
%ΔFS
Time post-catecholamine injection
(mins)
C
Base
B 10 20 30 40 50 60
-40
-20
0
20
40
%ΔFS
Time post-catecholamine injection
(mins)
Time post-catecholamine injection
(mins)
Rat Takotsubo Syndrome Model
2 Way ANOVA: A vs NA
Apex p<0.001 MLV p<0.001 Base p=ns
Paur et al Circulation 2012 126: 697-706
29. Whole-slice T2-weighted signal intensity (T2-w SI) data from normal
controls (A) and patients with acute Takotsubo syndrome (B).
Christopher Neil et al. Heart 2012;98:1278-1284
Does the heart fully recover following acute
Takotsubo syndrome?
Abnormal myocardial oedema persists at 3 months
Acute 3 months Control
33. Conclusions
• Complicated systemic biology
– Not myocardial infarction/plaque rupture
• Cardiac perspective
– High afterload and intracavity pressure acutely
– Negative inotropic pathway activation
• β2AR may play a role in some cases
• Cardioprotective
– Metabolic changes
– Vasospasm → ischaemia in subset
– Inflammation
• Systemic vascular responses
– Initially high followed by ‘dysregulation’
• Central HPA axis – level of gain
• Lots still to learn….