Different ATP-catabolism in reperfused adult and newborn rat hearts

Abstract

Age-dependent differences in the effects of ischemia and reperfusion on ATP breakdown were studied in perfused adult and newborn (10 days old) rat hearts. No-flow ischemia (15 min at 37, 30, or 23 degrees C) was applied and reperfusion (20 min at 37 degrees C) was studied after ischemia at 23 or 37 degrees C. Hypothermia during ischemia protected both age groups to a similar degree against ATP decline, which was linear with temperature. Reperfusion after normothermic ischemia resulted in higher ATP levels in newborn hearts with less release of ATP catabolites (purines). We found no age-related differences in lactate release but large differences in purine release. During normoxia, adult hearts released mainly urate (80% of total) and inosine (7%), but newborns released hypoxanthine (64%) and inosine (15%). Early during reperfusion adult hearts released inosine (58%) and adenosine (18%), but newborns released inosine (53%) and hypoxanthine (38%). These data suggested a lower activity of the potentially deleterious enzyme xanthine oxidoreductase in newborn hearts, which was confirmed by enzymatic assay. ATP-catabolite release during reperfusion was less in newborn than adult hearts, and this coincided with lower xanthine oxidase activity.

Inosine and hypoxanthine as novel biomarkers for cardiac ischemia: From bench to point-of-care

“…ATP-catabolite release during reperfusion was less in newborn than in the adults' hearts, and this coincided with lower xanthine oxidase activity. 16,17…”

“…14,15 It is noteworthy that de Jong and co-workers demonstrated in isolated adult or neonatal rat hearts that there were large age-related differences in purine release. 16,17 In the early phase of reperfusion, adult hearts released inosine (58%) and adenosine (18%), whereas newborns released inosine (53%) and hypoxanthine (38%). The authors interpreted the data as a lower activity of xanthine oxidoreductase (XO) in newborn hearts, which was confirmed by enzymatic assay.…”

“…ATP-catabolite release during reperfusion was less in newborn than in the adults' hearts, and this coincided with lower xanthine oxidase activity. 16,17 In another elegant study published in 1996, Mei and colleagues introduced a fast and sensitive method for a simultaneous determination of adenosine, inosine, hypoxanthine, xanthine, and uric acid in the interstitial fluid of canine myocardium. 18 They used microdialysis, microbore column high-performance liquid chromatography (HPLC), and a photo diode array detector, which allowed the simultaneous detection of UV absorbance at multiple wavelengths, allowing the detection of each compound at their maximal UV absorbance.…”

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“…Pacing does not alter the tissue high-energy phosphates level, index of energy balance, because the saturating supply of O 2 and substrate [16] allows tight coupling between ADP phosphorylation and ATP dephosphorylation. Although some ATP is likely converted to its catabolites even under baseline conditions, purine salvage and de novo purine synthesis compensate the loss of these compounds [17]. The higher level of inosine-5′-monophosphate in paced than control hearts may be due to adrenergic stimulation that enhances AMP conversion to inosine-5′-monophosphate by activating AMP deaminase [18].…”