Author + information
- Received January 23, 2019
- Revision received April 19, 2019
- Accepted April 20, 2019
- Published online August 26, 2019.
- Brian R. Weil, PhDa,b,∗ (, )
- George Techiryan, BSb,c,
- Gen Suzuki, MD, PhDb,c,
- Filip Konecny, DVM, PhDd and
- John M. Canty Jr., MDa,b,c,e,f
- aDepartment of Physiology and Biophysics, University at Buffalo, Buffalo, New York
- bThe Clinical and Translational Research Center, University at Buffalo, Buffalo, New York
- cDepartment of Medicine, University at Buffalo, Buffalo, New York
- dDepartment of Surgery, McMaster University, Hamilton, Ontario, Canada
- eVA WNY Health Care System, Buffalo, New York
- fDepartment of Biomedical Engineering, University at Buffalo, Buffalo, New York
- ↵∗Address for correspondence:
Dr. Brian R. Weil, Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Clinical Translational Research Center, Suite 7030, 875 Ellicott Street, Buffalo, New York 14203.
• A transient elevation in preload produces mechanical stretch-induced myocyte injury and measurable cardiac troponin I release that is associated with reversible contractile dysfunction and myocyte apoptosis.
• Using a porcine model of intermittent pressure overload, this study demonstrates that repetitive exposure to cyclical elevations in preload elicits significant myocyte loss, yet left ventricular systolic function is preserved and chamber dilatation is absent.
• Instead, myocardial remodeling characterized by myocyte hypertrophy and interstitial fibrosis produces a reduction in left ventricular diastolic compliance that protects the heart from subsequent stretch-induced myocyte injury.
• These results support a novel paradigm that links cardiac adaptations to repetitive stretch-induced injury with the pathogenesis of myocardial stiffening and may explain how reductions in left ventricular diastolic compliance can occur in the absence of sustained hypertension or anatomic hypertrophy.
Swine subjected to 2 weeks of repetitive pressure overload (RPO) exhibited significant myocyte loss, but left ventricular (LV) systolic function was preserved, and chamber dilatation did not occur. Instead, myocardial remodeling characterized by myocyte hypertrophy and interstitial fibrosis led to a marked reduction in LV diastolic compliance, which protected the heart from stretch-induced myocyte injury and preserved LV ejection fraction without anatomic LV hypertrophy. These results support a novel paradigm that links cardiac adaptations to RPO with the pathogenesis of reduced LV diastolic compliance and may explain how LV stiffening can occur in the absence of sustained hypertension or anatomic hypertrophy.
This study was supported by the National Heart Lung and Blood Institute (HL-055324, HL-061610, and F32HL-114335), the American Heart Association (17SDG33660200), the National Center for Advancing Translational Sciences (UL1TR001412), the Department of Veterans Affairs (1IO1BX002659), the New York State Department of Health (NYSTEM CO24351), and the Albert and Elizabeth Rekate Fund in Cardiovascular Medicine. Dr. Canty has been a consultant for Lantheus Medical Imaging, Inc. All other 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 January 23, 2019.
- Revision received April 19, 2019.
- Accepted April 20, 2019.
- 2019 The Authors