MECHANISMS OF IMMATURE MYOCARDIAL TOLERANCE TO ISCHEMIA - PHENOTYPIC DIFFERENCES IN ANTIOXIDANTS, STRESS PROTEINS, AND OXIDASES

Background. Previous work has suggested tolerance to ischemic injury i n newborn myocardium. Although various mechanisms for this protection have been proposed, a link between oxidant-antioxidant factors, stress protein expression, and protection from cardiac ischemia/reperfusion (I/R) injury has not been made in newborn myocardium. We hypothesized that newborn myocardial resistance to I/R is related to decreased oxyg en radical producing potential, increased free radical scavenging capa city and augmented stress protein expression. The purposes of the stud y were to examine in newborn and adult rat hearts (1) functional recov ery from I/R, (2) catalase and xanthine oxidase (XO) activities, and ( 3) heat shock protein 72 (HSP 72) expression. Methods. Isolated rat he arts (7 to 10 days versus 60 days) were perfused on a nonworking Lange ndorff apparatus at 60 mm Hg (Krebs-Henseleit buffer, pH 7.4, 37 degre es C) and subjected to 20 minutes of global ischemia and 40 minutes of reperfusion. Left ventricular developed pressure was recorded by usin g a left ventricular catheter. Catalase and XO were measured by means of standard assays, and HSP 72 was assessed with in situ immunohistoch emistry. Results. Newborn rat hearts had greater percentage functional recovery of left ventricular developed pressure after I/R (66.0% +/- 4.2% versus 44.3% +/- 3.5%; p < 0.05). The newborn myocardium also had increased catalase activity (1027.9 +/- 20.6 units/gm versus 707.3 +/ - 38.7 units/gm; p < 0.05), whereas the activity of XO was decreased r elative to the adult (0.23 +/- 0.01 mU/gm versus 7.6 + 1.4 mU/gm; p < 0.05). Furthermore, the expression of HSP 72 was greater in the newbor n than the adult control. Conclusions. Relative to adult hearts, newbo rn rat hearts are more tolerant to a global ischemic insult followed b y reperfusion. This improved functional recovery is associated with de creased oxidant production potential (XO), increased scavenging capaci ty (catalase), and augmented stress protein expression (HSP 72).