Author + information
- Received April 11, 2017
- Revision received October 8, 2017
- Accepted October 10, 2017
- Published online April 30, 2018.
- Sven Y. Surikow, BHlthSc (Hons)a,b,
- Thanh H. Nguyen, MD, MMedSci, PhDa,b,
- Irene Stafford, BSca,
- Matthew Chapman, BSc, MClinSci, DMU, CEPIAa,
- Sujith Chacko, MBBSa,
- Kuljit Singh, MBBS, PhDa,b,
- Giovanni Licari, BSc, PhDb,
- Betty Raman, MBBSa,b,
- Darren J. Kelly, PhDc,
- Yuan Zhang, MBBS, PhDc,
- Mark T. Waddingham, BSc (Hons), PhDc,
- Doan T. Ngo, BPharm, PhDa,
- Alexander P. Batea,
- Su Jen Chua, MBBSa,
- Michael P. Frenneaux, MDd and
- John D. Horowitz, MBBS, BMedSci(Hons), PhDa,b,∗ ()
- aThe Queen Elizabeth Hospital, Department of Cardiology, University of Adelaide, South Australia, Australia
- bBasil Hetzel Institute, Adelaide, South Australia, Australia
- cDepartment of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Australia
- dUniversity of East Anglia, Norfolk, United Kingdom
- ↵∗Address for correspondence:
Dr. John D. Horowitz, Cardiology Unit, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South, SA 5011, Australia.
• Treatment of female rats with a single dose of isoproterenol results in apical hypokinesis mimicking Takotsubo syndrome
• Myocardial inflammation includes increased content of 3-nitrotyrosine and poly(ADP-ribose), indicating nitrosative stress and PARP-1 activation, respectively
• Pretreatment with 3-aminobenzamide (a PARP-1 inhibitor) attenuates negative inotropic changes
• We conclude that the peroxynitrite/PARP-1 cascade contributed to negative inotropy in this model of Takotsubo syndrome, consistent with the limited data available in patients
Previous studies have shown that patients with Takotsubo syndrome (TS) have supranormal nitric oxide signaling, and post-mortem studies of TS heart samples revealed nitrosative stress. Therefore, we first showed in a female rat model that isoproterenol induces TS-like echocardiographic changes, evidence of nitrosative stress, and consequent activation of the energy-depleting enzyme poly(ADP-ribose) polymerase-1. We subsequently showed that pre-treatment with an inhibitor of poly(ADP-ribose) polymerase-1 ameliorated contractile abnormalities. These findings thus add to previous reports of aberrant β-adrenoceptor signaling (coupled with nitric oxide synthase activation) to elucidate mechanisms of impaired cardiac function in TS and point to potential methods of treatment.
This work was funded in part by a Project Grant from the National Health and Medical Research Council (Australia). Mr. Surikow, Dr. Raman, and Dr. Singh were recipients of Postgraduate Research Scholarships from the University of Adelaide (Mr. Surikow and Dr. Singh) and from the Cardiac Society of Australia and New Zealand (Dr. Raman). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received April 11, 2017.
- Revision received October 8, 2017.
- Accepted October 10, 2017.
- 2018 The Authors