Myocardial injury after hypoxia in immature, adult and aged rats

Abstract

We evaluated the abilities of isolated perfused hearts from immature (IM) (2.5–3 months), ADULT (11–13 months) and OLD (24–26 months) Fischer 344 rats to tolerate and recover from oxygen deprivation. Hearts were perfused at 60 mmHg for a 30-minute prehypoxic period with oxygenated buffer supplemented with 10 mM glucose (+insulin) and 2 mM acetate, then 30 minutes with substrate-free, hypoxic buffer gassed with 95% N2:5% CO₂, and finally reoxygenated for an additional 45 minutes with the same buffer used during the prehypoxic period. During prehypoxia, all groups were similar in ventricular mechanical function, glycogen content, high-energy phosphates (HEP), reduced glutathione (GSH), Ca⁺⁺ content, and mitochondrial state 3 rates. At the end of the hypoxic period, glycogen levels were similar and almost completely depleted in all groups, HEP were lower (p<0.05) in ADULT vs other groups, mitochondrial state 3 rates were decreased (24%, p<0.05) only in ADULT, and GSH was depleted by 34% in IM vs only 13% in OLD (p<0.05). After 45 minutes of reoxygenation, IM and OLD had recovered 48% and 45% of their respective prehypoxic function which was two-fold greater than the 23% recovery by ADULT. Loss of cytosolic enzymes, an indicator of sarcolemmal damage, was estimated by measuring lactate dehydrogenase (LDH) release. LDH release and Ca⁺⁺ content during reoxygenation in IM were only about half of that observed in ADULT or OLD. We conclude that immature and aged hearts tolerate and recover from hypoxia better than hearts from adults, and that the sarcolemmal membranes of immature rat hearts are less susceptible to damage from hypoxic stress than those of either older group.