CALCIUM IMPROVES MECHANICAL FUNCTION AND CARBOHYDRATE-METABOLISM FOLLOWING ISCHEMIA IN ISOLATED BIVENTRICULAR WORKING HEARTS FROM IMMATURE RABBITS

In the adult heart an increase in extracellular [Ca2+] can contribute to the severity of ischemic injury. While experimental studies have su ggested that the immature heart is more resistant to ischemia than the mature heart, the reasons for this are unclear, In this study, we det ermined the effects of increasing perfusate [Ca2+] from 1.25 to 2.5 mM on reperfusion recovery of mechanical function and energy substrate m etabolism following ischemia, Isolated bi-ventricular working hearts f rom 2-week-old rabbits were subjected to a 55-min period of global isc hemia followed by 40 min of aerobic reperfusion. Perfusate contained 1 1 mM glucose, 0.5 mM lactate, and 1.2 mM palmitate, containing either: (i) 1.25 mM Ca2+ throughout the perfusion period (n=22), (ii) 1.25 mM Ca2+ prior to and during ischemia and 2.5 mM Ca2+ following ischemia (n=19), or (iii) 2.5 mM Ca2+ throughout the perfusion period (n=18), I n hearts perfused with 1.25 mM Ca2+ throughout, a 57% recovery of prei schemic function was seen following ischemia. If [Ca2+] was increased to 2.5 mM during reperfusion a significant improvement of function was seen (hearts recovered 127% of preischemic function), A concentration of 2.5 mM Ca2+ throughout the perfusion resulted in an increase in bo th pre- and post-ischemic function compared to hearts perfused with 1. 25 mM Ca2+ throughout, In both experimental groups reperfused with 2.5 mM Ca2+ a greater than 200% increase in both glucose and lactate oxid ation was seen during reperfusion, Fatty acid oxidation rates also ret urned to pre-ischemic levels in both groups reperfused with 2.5 mM Ca2 +, while rates returned to only 53% in hearts reperfused with 1.25 mM Ca2+, As a result, increasing [Ca2+] from 1.25 to 2.5 mM resulted in a 100% increase in ATP production rates during reperfusion, In conclusi on, this study demonstrates that increasing [Ca2+] significantly impro ves post-ischemic recovery of function in isolated bi-ventricular work ing immature rabbit hearts subjected to a 55-min period of ischemia. T he beneficial effects of Ca2+ in these immature hearts may be due to b oth a direct inotropic effect and a marked increase in carbohydrate ox idation and ATP production during reperfusion. (C) 1996 Academic Press Limited.