Abstract 3671: Role of Myoglobin in the Postischemic Heart
Myoglobin (Mb) is an essential cardiac hemoprotein that facilitates oxygen transport and scavenges nitric oxide/reactive oxygen species. However, there exists controversy regarding the cellular function of Mb during myocardial ischemia/reperfusion injury (I/R). Utilizing homologous recombination and transgenic technology, mouse models with loss (Mb−/−) and gain (TgMb) of Mb function have previously be engineered. In order to investigate the role of Mb in I/R, an in vivo regional myocardial I/R study (30-min coronary ligation and 24-hr reperfusion) was undertaken. To measure in vivo myocardial pO2 at baseline and during I/R, real-time EPR oximetry with the oxygen-sensing probe LiPc was performed. Following 24-hr reperfusion, there was no difference in the area at risk (AAR) between groups; however, myocardial infarct area (IA) was much smaller in Mb−/− mice compared to respective control mice (Table⇓). Prominent, early mortality was observed in TgMb mice within 60-min of reperfusion (5 of 6), due to arrhythmia or heart failure. EPR oximetry with intramyocardial LiPc in the area at risk showed that the hearts of Mb−/− mice have a 20% higher basal myocardial pO2. Overshoot in myocardial oxygenation during reperfusion was seen in WT but not in Mb−/− mice. In contrast, both TgMb and nontransgenic (NTg) mice had comparable overshoot with myocardial oxygenation during reperfusion. Thus, in a model of I/R absence of Mb results in enhanced myocardial protection with decreased infarct size and prevents postischemic hyperoxygenation, while with excess Mb, postischemic hyperoxygenation persists with increased susceptibility to myocardial I/R injury and early reperfusion death. Collectively, this data provides evidence that Mb may serve a critical role in the pathophysiology underlying myocardial ischemia/reperfusion injury.