Author + information
- Received January 26, 2018
- Revision received March 28, 2018
- Accepted April 3, 2018
- Published online June 18, 2018.
- Brian R. Weil, PhDa,b,∗ (, )@UBuffaloCTSI@UBuffalo,
- Gen Suzuki, MD, PhDb,c,
- Rebeccah F. Young, MAb,c,
- Vijay Iyer, MD, PhDb,c and
- John M. Canty Jr., MDa,b,c,d,e
- aDepartment of Physiology and Biophysics, University at Buffalo, Buffalo, New York
- bClinical and Translational Research Center of the University at Buffalo, Buffalo, New York
- cDepartment of Medicine, Division of Cardiovascular Medicine, University at Buffalo, Buffalo, New York
- dDepartment of Biomedical Engineering, University at Buffalo, Buffalo, New York
- eVA WNY Health Care System, 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.
Background The authors previously demonstrated that brief ischemia elicits cardiac troponin I (cTnI) release and myocyte apoptosis in the absence of necrosis. It remains uncertain whether other pathophysiological stresses can produce apoptosis and transient cTnI release without ischemia.
Objectives This study sought to determine whether a transient increase in left ventricular (LV) preload elicits cTnI release in the absence of ischemia.
Methods Propofol-anesthetized swine (N = 13) received intravenous phenylephrine (PE) (300 μg/min) for 1 h to increase left ventricular end-diastolic pressure (LVEDP) to ∼30 mm Hg. Serial cTnI and echocardiographic function were assessed for 24 h, and myocardial tissue was analyzed for apoptosis and necrosis.
Results PE infusion increased systolic blood pressure from 137 ± 14 mm Hg to 192 ± 11 mm Hg (mean ± SD; p < 0.001) and increased LVEDP from 17 ± 2 mm Hg to 30 ± 5 mm Hg (p < 0.001). Myocardial flow measurements demonstrated no evidence of ischemia. Hemodynamics normalized rapidly after PE, but LV ejection fraction remained depressed (32 ± 21% vs. 58 ± 7%; p < 0.01) with normalization after 24 h (51 ± 16%; p = 0.31). Baseline transcoronary cTnI release was low (16 ± 20 ng/l) but increased to 856 ± 956 ng/l (p = 0.01) 1 h after LVEDP elevation. Circulating cTnI rose above the 99th percentile within 30 min and remained elevated at 24 h (1,462 ± 1,691 ng/l). Pathological analysis demonstrated myocyte apoptosis at 3 h (31.3 ± 11.9 myocytes/cm2 vs. 4.6 ± 3.7 myocytes/cm2; p < 0.01), that normalized after 24 h (6.2 ± 5.6 myocytes/cm2; p = 0.46) without histological necrosis.
Conclusions Transient elevations of LVEDP lead to cTnI release, apoptosis, and reversible stretch-induced stunning in the absence of ischemia. Thus, preload-induced myocyte injury may explain many cTnI elevations seen in the absence of clinical signs or symptoms of myocardial ischemia.
- cardiac troponin I
- cardiomyocyte apoptosis
- left ventricular preload
- myocardial stretch
- myocardial stunning
- pressure overload
Funded 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), and the Albert and Elizabeth Rekate Fund in Cardiovascular Medicine. Dr. Iyer has been a proctor for Edwards Lifesciences, Boston Scientific, and Medtronic. Dr. Canty has been a consultant for Lantheus Medical Imaging. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received January 26, 2018.
- Revision received March 28, 2018.
- Accepted April 3, 2018.
- 2018 American College of Cardiology Foundation