Reduced cytosolic Ca2+ loading and improved cardiac function after cardioplegic cold storage of guinea pig isolated hearts

Abstract

Background - Hypothermia is cardioprotective, but it causes Ca2+ loading and reduced function on rewarming. The aim was to associate changes in cytosolic Ca2+ with function in intact hearts before, during, and after cold storage with or without cardioplegia (CP). Methods and Results Guinea pig hearts were initially perfused at 37°C with Krebs-Ringer's (KR) solution (in mmol/L: Ca2+ 2.5, K+ 5, Mg2+ 2.4). One group was perfused with CP solution (Ca2+ 2.5, K+ 18, Mg2+ 7.2) during cooling and storage at 3°C for 4 hours; another was perfused with KR. LV pressure (LVP), dP/dt, O2 consumption, and cardiac efficiency were monitored. Cytosolic phasic [Ca2+] was calculated from indo 1 fluorescence signals obtained at the LV free wall. Cooling with KR increased diastolic and phasic [Ca2+], whereas cooling with CP suppressed phasic [Ca2+] and reduced the rise in diastolic [Ca2+]. Reperfusion with warm KR increased phasic [Ca2+] 86% more after CP at 20 minutes and did not increase diastolic [Ca2+] at 60 minutes, compared with a 20% increase in phasic [Ca2+] after KR. During early and later reperfusion after CP, there was a 126% and 50% better return of LVP than after KR; during later reperfusion, O2 consumption was 23% higher and cardiac efficiency was 38% higher after CP than after KR. Conclusions - CP decreases the rise in cardiac diastolic [Ca2+] observed during cold storage in KR. Decreased diastolic [Ca2+] and increased systolic [Ca2+] after CP improves function on reperfusion because of reduced Ca2+ loading during and immediately after cold CP storage.