This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Abdallah, Y. Articles by Piper, H. M. PubMed Articles by Abdallah, Y. Articles by Piper, H. M.

(Circulation. 2006;114:II_1202.)
© 2006 American Heart Association, Inc.

Session X - Best Original Resuscitation Science: Poster Session (Part 2)

Abstract 71: Reperfusion-Induced Hypercontracture of Cardiomyocytes is Secondary to SR-Driven Cytosolic Ca²⁺ Oscillations and Mitochondrial Permeability Transition

Yaser Abdallah; Thomas Suski; Claudia Schäfer; Maher Said; Dragan Gligorievski; Sascha Kasseckert; Hans Michael Piper

Institute of Physiology, Giessen, Germany

Introduction: We showed previously that reperfusion causes hypercontracture and necrosis of cardiomyocytes due to oscillatory elevations of cytosolic Ca²⁺ originating from the sarcoplasmic reticulum (SR). It has also been shown that mitochondrial permeability transition (MPT) induces cell death in reperfused myocardium. We now investigated if SR-triggered Ca²⁺ oscillations and MPT are causally connected in signalling towards reperfusion-induced cardiomyocyte hyper-contracture.

Methods: To simulate ischemia and reperfusion, isolated cardiac myocytes from adult rat were superfused anoxically (pH 6.4) and then reperfused with a normoxic puffer (pH 7.4). Induction of MPT was detected in whole cells by the calcein loading procedure. Cytosolic Ca²⁺ was measured by use of fura-2.

Results: During simulated ischemia, no significant change in calcein fluorescence was observed. Reperfusion induced a marked decline in calcein fluorescence, which reflects induction of MPT. Concomitantly, reperfused cells developed hypercontracture. Application of the MPT inhibitor cyclosporine (500 nM) or inhibition of SR-Ca²⁺ release with ryanodine (3 µM) reduced the decline in calcein fluorescence and hypercontracture (calcein fluorescence as % of end-anoxic value after 5 min reperfusion: control: 42.2±2.4; cyclosporine: 90.5±1.8*; ryanodine: 86.8±1.5*; n=20; *p<0.05 vs. control; cell length as % of end-anoxic after 5 min reperfusion; control: 46.8±1.6; cyclosporine: 88.0±1.8*; ryanodine: 94.8±2.0*; n=20; *p<0.05).

Conclusions: Induction of MPT is involved in the development of reperfusion-induced hypercontracture of cardiac myocytes. It is triggered by oscillations of cytosolic Ca²⁺ originating from the SR during the early phase of reperfusion.

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Abdallah, Y. Articles by Piper, H. M. PubMed Articles by Abdallah, Y. Articles by Piper, H. M.