Mechanisms of immature myocardial tolerance to ischemia: Phenotypic differences in antioxidants, stress proteins, and oxidases

Abstract

Previous work has suggested tolerance to ischemic injury in 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 total newborn myocardial resistance to I/R is related to decreased oxygen radical producing potential, increased free radical scavenging capacity and augmented stress protein expression. The purposes of the study were to examine in newborn and adult rat hearts (1) functional recovery from I/R, (2) catalase and xanthine oxidase (XO) activities, and (3) heat shock protein 72 (HSP 72) expression. Isolated rat hearts (7 to 10 days versus 60 days) were perfused on a nonworking Langendorff apparatus at 60 mm Hg (Krebs-Henseleit buffer, pH 7.4, 37 degrees C) and subjected to 20 minutes of global ischemia and 40 minutes of reperfusion. Left ventricular developed pressure was recorded by using a left ventricular catheter. Catalase and XO were measured by means of standard assays, and HSP 72 was assessed with in situ immunohistochemistry. 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 relative 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 newborn than the adult control. Relative to adult hearts, newborn rat hearts are more tolerant to a global ischemic insult followed by reperfusion. This improved functional recovery is associated with decreased oxidant production potential (XO), increased scavenging capacity (catalase), and augmented stress protein expression (HSP 72).