© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Preservation of myofilament calcium responsiveness underlies protection against myocardial stunning by ischemic preconditioning1
aSection of Molecular and Cellular Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
bCentro de Investigaciones Cardiovasculares. Facultad de Ciencias Médicas, de La Plata (UNLP), La Plata, Buenos Aires, Argentina
* Corresponding author. Room 844, Ross Building, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA. Tel.: +1-410-955-2776; Fax: +1-410-955-7953. E-mail address: marban@welchlink.welch.jhu.edu
Objective: Whereas diminution of infarct size by ischemic preconditioning (IP) is well-accepted, protection against stunning is controversial. Since stunning is characterized by decreased myofilament Ca2+ responsiveness, we investigated whether IP would preserve myofilament responsiveness in a model of stunning. Methods: Rat hearts were retrogradely perfused with Krebs–Henseleit (K–H) solution for 20 min and then subjected to 20 min of no-flow global ischemia, followed by 20 min of reperfusion in the absence (stunning) or in the presence (IP) of a previous 5-min period of ischemia followed by 15 min of reperfusion. A group of hearts perfused under non-ischemic conditions served as control. Thin ventricular trabeculae were dissected from each of the experimental groups and loaded with fura-2 to measure intracellular calcium concentration ([Ca2+]i) and developed force. Results: After 20 min of reperfusion, left ventricular developed pressure decreased in stunned hearts to 61±5% of control (P<0.01), whereas recovery was complete in the IP hearts (97±4%). Steady-state [Ca2+]i–force relationships revealed a decreased maximal Ca2+-activated force in stunned hearts relative to control, but no change in the IP group. The Ca2+ required for 50% activation increased in stunning but not in IP. Conclusions: These results show that the decrease in myofilament responsiveness that characterizes stunning is prevented by ischemic preconditioning.
KEYWORDS Ischemia; Reperfusion; Stunning; Calcium (cellular); Preconditioning
1 Abbreviations: IP, ischemic preconditioning, LVDP, left ventricular developed pressure, [Ca2+]i, intracellular calcium concentration, [Ca2+]o, extracellular calcium concentration, K–H, Krebs–Henseleit, TnI, troponin I.
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