Participation of Na/Ca‐exchanger and sarcoplasmic reticulum in the high [K]o‐protection against ischaemia‐reperfusion dysfunction in rat hearts

Aim: Na/Ca‐exchanger (NCX) and sarcoplasmic reticulum (SR) roles during the protection by a cardioplegic solution (25 mm K and 0.5 mm Ca, CPG) against ischaemia‐reperfusion was studied. Methods: Contractile performance (CP) and high energy phosphates contents (HEP) were evaluated in isolated ventricles from rats. They were pre‐treated with Krebs (C) or CPG and submitted to no‐flow ischaemia and reperfusion (I–R). KB‐R7943 5 μm (inhibitor of NCX in reverse mode), 8 mm caffeine and ionic changes were used pre‐ischaemically to evaluate each pathway role. Results: During R, CP recovered to 77 ± 8% of basal in CPG‐hearts vs. 55 ± 8% (P < 0.05) in C‐ones. CPG avoided the increases in end diastolic pressure (LVEDP) and in PCr/ATP ratio during I–R. Low Na]_o (78 mm ) under both, CPG‐2 mm Ca and C, increased further the LVEDP during I–R. LVEDP was also transiently increased by caffeine‐CPG, but not modified by KB‐R7943. The recovery of CP during reperfusion of CPG‐hearts was decreased either, by caffeine (to ～75%), low Na]_o‐2 mm Ca‐CPG (to ～40%) and KB‐R7943 (to ～16%). Conclusions: CPG protected hearts from ischaemic contracture by attenuating the fall in ATP and removing diastolic Ca by means of NCX in forward mode. Moreover, CPG induces higher CP recovery during reperfusion by participation of SR and NCX in reverse mode. This work remarks the use of CPG based on the functional role of these Ca handling‐mechanisms in a pathophysiological condition as ischaemia‐reperfusion.