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ORIGINAL ARTICLE

Influence of Ischemic Preconditioning on Intracellular Sodium, pH, and Cellular Energy Status in Isolated Perfused Heart

Andriy Babsky^*,1, Shahryar Hekmatyar^*, Suzanne Wehrli^,, Nicolai Doliba^,, Mary Osbakken^,, and Navin Bansal^*,1

^* Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104;
Children's Hospital, Philadelphia, Pennsylvania 19104;
Department of Biochemistry/Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104; and
Aventis, Bridgewater, New Jersey 08807

The possible relationships between intracellular Na⁺ (Na_i⁺), bioenergetic status and intracellular pH (pH_i) in the mechanism for ischemic preconditioning were studied using ²³Na and ³¹P magnetic resonance spectroscopy in isolated Langendorff perfused rat heart. The ischemic preconditioning (three 5-min ischemic episodes followed by two 5-min and one 10-min period of reperfusion) prior to prolonged ischemia (20 min stop-flow) resulted in a decrease in ischemic acidosis and faster and complete recovery of cardiac function (ventricular developed pressure and heart rate) after 30 min of reperfusion. The response of Na_i during ischemia in the preconditioned hearts was characterized by an increase in Na_i⁺ at the end of preconditioning and an accelerated decrease during the first few minutes of reperfusion. During post-ischemic reperfusion, bioenergetic parameters (PCr/P_i and ßATP/P_i ratios) were partly recovered without any significant difference between control and preconditioned hearts. The reduced acidosis during prolonged ischemia and the accelerated decrease in Na_i⁺ during reperfusion in the preconditioned hearts suggest activation of Na⁺/H⁺ exchanger and other ion transport systems during preconditioning, which may protect the heart from intracellular acidosis during prolonged ischemia, and result in better recovery of mechanical function (LVDP and heart rate) during post-ischemic reperfusion.

Key Words: perfused heart • preconditioning • sodium • NMR

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