Enhanced NO signaling in patients with Takotsubo cardiomyopathy: short-term pain, long-term gain?
OBJECTIVE
Little information is available concerning the mechanism(s) underlying Takotsubo cardiomyopathy (TTC), other than evidence of associated catecholamine secretion. Given the known effects of catecholamines on endothelial function, we tested the hypothesis that TTC might also be associated with impairment of nitric oxide (NO) signaling. We now report an evaluation of NO signaling in TTC patients (vs. aged-matched controls) in relation to (a) severity of the acute attack and (b) rate of recovery.


METHODS
In 56 patients with TTC, we utilized (1) platelet responsiveness to NO and (2) plasma levels of asymmetric dimethylarginine (ADMA) as indices of integrity of the cyclic guanosine monophosphate (cGMP) pathway. Additionally, endothelial progenitor cell (EPC) counts, which are partially NO-dependent, were evaluated. These parameters were measured at the time of diagnosis and 3 months thereafter, and compared with an aging female cohort (n = 81).


RESULTS
The data suggested that both NO generation and effect were accentuated in TTC patients: ADMA concentrations were lower (p = 0.003), and responsiveness to NO substantially greater (p = 0.0001) than in controls both acutely and after 3 months. Markers of severity of TTC attacks directly correlated with NO responsiveness, while extent of recovery at 3 months varied inversely with ADMA concentrations.


CONCLUSIONS
TTC is associated with intensification of NO signaling relative to that in normal age-matched females. Our data are consistent with this intensified signal's potential contribution to the extent of initial myocardial injury, but conversely to accelerated recovery.
The Queen Elizabeth Hospital, Department of Cardiology, The University of Adelaide, Adelaide, Australia.
Thanh H
TH
Nguyen
Christopher J
CJ
Neil
Aaron L
AL
Sverdlov
Doan T
DT
Ngo
Wai P
WP
Chan
Tamila
T
Heresztyn
Yuliy Y
YY
Chirkov
Dimitrios
D
Tsikas
Michael P
MP
Frenneaux
John D
JD
Horowitz
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D015398:Signal Transduction; D054549:Takotsubo Cardiomyopathy / Q000378:metabolism*
D009569:Nitric Oxide