Ischemic and anesthetic preconditioning reduces cytosolic [Ca2+] and improves Ca2+responses in intact hearts

Abstract

Ca+ loading during reperfusion after myocardial ischemia is linked to reduced cardiac function. Like ischemic preconditioning (IPC), a volatile anesthetic given briefly before ischemia can reduce reperfusion injury. We determined whether IPC and sevoflurane preconditioning (SPC) before ischemia equivalently improve mechanical and metabolic function, reduce cytosolic Ca2+ loading, and improve myocardial Ca2+ responsiveness. Four groups of guinea pig isolated hearts were perfused: no ischemia, no treatment before 30-min global ischemia and 60-min reperfusion (control), IPC (two 2-min occlusions) before ischemia, and SPC (3.5 vol%, two 2-min exposures) before ischemia. Intracellular Ca2+ concentration ([Ca2+]i) was measured at the left ventricular (LV) free wall with the fluorescent probe indo 1. Ca2+ responsiveness was assessed by changing extracellular [Ca2+]. In control hearts, initial reperfusion increased diastolic [Ca2+] and diastolic LV pressure (LVP), and the maximal and minimal derivatives of LVP (dLVP/d t max and dLVP/d t min, respectively), O2consumption, and cardiac efficiency (CE). Throughout reperfusion, IPC and SPC similarly reduced ischemic contracture, ventricular fibrillation, and enzyme release, attenuated rises in systolic and diastolic [Ca2+], improved contractile and relaxation indexes, O2 consumption, and CE, and reduced infarct size. Diastolic [Ca2+] at 50% dLVP/d t min was right shifted by 32–53 ± 8 nM after 30-min reperfusion for all groups. Phasic [Ca2+] at 50% dLVP/d t max was not altered in control but was left shifted by −235 ± 40 nM [Ca2+] after IPC and by −135 ± 20 nM [Ca2+] after SPC. Both SPC and IPC similarly reduce Ca2+ loading, while augmenting contractile responsiveness to Ca2+, improving postischemia cardiac function and attenuating permanent damage.