Although the specific basal metabolic rate increases with decreasing body mass, newborn mammals are known to exhibit a higher tolerance to hypoxia/ischemia than adults. This is partly due to their ability to reduce energy demands in response to impaired supply. The so-called "hypoxic hypometabolism" might be explained as a temporary return to a prenatal metabolic state where the usual metabolic size relationship is suppressed and the fetus exhibits an "adult-like" specific metabolic rate. To study the interrelationship of body size, metabolic rate, and ischemia tolerance within and across species, both myocardial thin slices (to determine aerobic metabolic rates) and isolated non-perfused hearts (to assess ischemic "dying curves") from neonatal, juvenile, and adult rats were measured by microcalorimetry (2277 Thermal Activity Monitor, ThermoMetric, Sweden) and the results compared with earlier findings on mouse hearts. The aerobic tissue metabolic rates of myocardial samples from both species decreased with increasing body mass, according to the overall metabolic size relationship. Moreover, a slowing-down of the ischemic "dying curves" with decreasing body mass was found, reflecting the increasing hypoxia/ischemia tolerance. However, the amount of heat produced during ischemia turned out to be higher in neonatal rats than in juvenile mice, or in juvenile rats than in adult mice, respectively, despite nearly identical body and organ weights. The factor by which the ischemia tolerance of rats exceeds that of mice of comparable size, corresponds to the difference in specific basal metabolic rates to be expected between adult individuals of the same species. This is suggestive of a temporary return to an "adult-like" metabolic level underlying the elevated hypoxia/ischemia tolerance in neonatal and juvenile mammals. (C) 2004 Elsevier B.V. All rights reserved.