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This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/H1699    most recent 01033.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Hagihara, H. Articles by Takaki, M. Search for Related Content PubMed PubMed Citation Articles by Hagihara, H. Articles by Takaki, M.

Na⁺/Ca²⁺ exchange inhibition protects the rat heart from ischemia-reperfusion injury by blocking energy-wasting processes

Departments of ¹Physiology II and ²Thoracic-Cardiovascular Surgery, Nara Medical University, Kashihara, Nara; and ³Department of Neurology and Neurosurgery, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan

Submitted 8 October 2004 ; accepted in final form 22 December 2004

We have recently reported that exposure of rat hearts to high Ca²⁺ produces a Ca²⁺ overload-induced contractile failure in rat hearts, which was associated with proteolysis of -fodrin. We hypothesized that contractile failure after ischemia-reperfusion (I/R) is similar to that after high Ca²⁺ infusion. To test this hypothesis, we investigated left ventricular (LV) mechanical work and energetics in the cross-circulated rat hearts, which were subjected to 15 min global ischemia and 60 min reperfusion. Sixty minutes after I/R, mean systolic pressure-volume area (PVA; a total mechanical energy per beat) at midrange LV volume (mLVV) (PVA_mLVV) was significantly decreased from 5.89 ± 1.55 to 3.83 ± 1.16 mmHg·ml·beat^–1·g^–1 (n = 6). Mean myocardial oxygen consumption per beat (VO₂) intercept of (VO₂-PVA linear relation was significantly decreased from 0.21 ± 0.05 to 0.15 ± 0.03 µl O₂·beat^–1·g^–1 without change in its slope. Initial 30-min reperfusion with a Na⁺/Ca²⁺ exchanger (NCX) inhibitor KB-R7943 (KBR; 10 µmol/l) significantly reduced the decrease in mean PVA_mLVV and VO₂ intercept (n = 6). Although VO₂ for the Ca²⁺ handling was finally decreased, it transiently but significantly increased from the control for 10–15 min after I/R. This increase in VO₂ for the Ca²⁺ handling was completely blocked by KBR, suggesting an inhibition of reverse-mode NCX by KBR. -Fodrin proteolysis, which was significantly increased after I/R, was also significantly reduced by KBR. Our study shows that the contractile failure after I/R is similar to that after high Ca²⁺ infusion, although the contribution of reverse-mode NCX to the contractile failure is different. An inhibition of reverse-mode NCX during initial reperfusion protects the heart against reperfusion injury.

calcium overload; mechanoenergetics; KB-R7943; -fodrin

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